NOTES

Patents Claiming Genetically Engineered Inventions: A Few Thoughts on Obtaining Broad Property Rights

  Introduction

The United States Constitution authorizes Congress to promote the useful arts through the granting of exclusive licenses to inventors.⁽¹⁾ Congress exercised this power early in the nation's history with the passage of the first patent statute in 1790.⁽²⁾ Patents protect the property interests of inventors by conferring an exclusive right to preventing others from making, selling, offering for sale, using, or importing their inventions for a term running from the date the patent is issued until twenty years from the date the patent application was filed.⁽³⁾ Thus, the ownership of a patent gives one the right to prevent others from "practicing" the invention,⁽⁴⁾ for the term of the patent.⁽⁵⁾

The United States Patent and Trademark Office (PTO) issues approximately 100,000 patents annually, with the majority being awarded to inventors who are citizens of the United States.⁽⁶⁾ The issuance rate of patents to United States inventors is directly related to research and development expenditures and is thus one measure of the nation's economic competitiveness in the world marketplace.⁽⁷⁾

A.  Obtaining a Patent from the United States Patent and Trademark Office

Patents are obtained through a process called "prosecution."⁽⁸⁾ The patent applicant, or an agent of the applicant, drafts an application and files it with the PTO where it is reviewed by an examiner.⁽⁹⁾ In order for a patent to be granted, the subject invention must consist of patentable subject matter⁽¹⁰⁾ and must be novel,⁽¹¹⁾ useful,⁽¹²⁾ and nonobvious.⁽¹³⁾ Further, the specification⁽¹⁴⁾ must provide a "written description of the invention,"⁽¹⁵⁾ disclose sufficient information to enable one skilled in the relevant art to make and use the invention,⁽¹⁶⁾ and must present the "best mode" contemplated by the inventor for the design or operation of that invention.⁽¹⁷⁾ These are referred to as the written description, enablement, and best mode requirements, respectively.⁽¹⁸⁾ At the PTO, an examiner reviews the patent application and determines whether the invention meets all of the legal requirements of patentability.⁽¹⁹⁾

Patent prosecution generally involves a series of negotiations with the examiner over the scope of the patent.⁽²⁰⁾ Inventors normally seek to obtain broad patent rights that encompass numerous variations of their inventions,⁽²¹⁾ while examiners attempt to limit the inventions in accordance with the legal requirements of patentability.⁽²²⁾ These negotiations generally focus almost exclusively on the claims,⁽²³⁾ and end when either the examiner "allows" the claims in the application,⁽²⁴⁾ resulting in patent issuance, or when the patent examiner issues a "final" rejection.⁽²⁵⁾ After a patent application has been rejected twice or a final rejection has been issued, the applicant may appeal to the Patent Office's Board of Patent Appeals and Interferences.⁽²⁶⁾ In the event of an unfavorable decision by the Board of Patent Appeals and Interferences (Board), the inventor may appeal the Boards decision to the Court of Appeals for the Federal Circuit (Federal Circuit).⁽²⁷⁾

Since 1982, the Federal Circuit has been the only circuit court that hears patent cases and controversies involving the legal requirements of patentability and the interpretation of issued patents.⁽²⁸⁾ Further, because patent cases are rarely heard by the United States Supreme Court, the Federal Circuit is generally viewed as the court of last resort for patent issues.⁽²⁹⁾

B.  United States Patent Applications

A complete patent application consists of a specification with one or more claims, drawings, if necessary,⁽³⁰⁾ an oath or declaration, and the appropriate filing fee.⁽³¹⁾ The specification⁽³²⁾ and drawings must disclose sufficient information "to enable any person skilled in the art to which it pertains . . . to make and use the [invention]"⁽³³⁾ and must present "the best mode contemplated by the inventor of carrying out his invention."⁽³⁴⁾

The specification generally consists of several subsections, each of which serve specific functions.⁽³⁵⁾ A Summary of the Invention (Summary) is normally included and contains a brief description of the invention in general terms.⁽³⁶⁾ While the Summary may be written in a variety of formats, it generally reflects the content of the claims and explains the invention in a manner understandable to a judge or jury unfamiliar with the relevant art.⁽³⁷⁾

The Detailed Description⁽³⁸⁾ discloses the specific elements of the invention and explains how to make or use the invention in sufficient detail to meet the requirements of 35 U.S.C. § 112, paragraph one.⁽³⁹⁾ In addition, particular embodiments and examples may be included in the Detailed Description.⁽⁴⁰⁾ Patent applications are thus drafted with an eye toward litigation, in that generally one section is intended to describe the invention in lay terms, and another section discloses the invention in sufficient detail to enable one skilled in the art to practice that invention.⁽⁴¹⁾

"The claims are the [single] most important part of a patent application."⁽⁴²⁾ A patent's claims determine the boundaries of the invention and thus define the invention for both prosecution and infringement purposes.⁽⁴³⁾ While their format may vary,⁽⁴⁴⁾ all claims must clearly define what the inventor considers to be his or her invention.⁽⁴⁵⁾

Applicants generally submit claims that reflect the subject matter that was actually invented and that are intended to generate broad property rights.⁽⁴⁶⁾ These claims are limited in scope, however, by the amount of prior work done by others in the field,⁽⁴⁷⁾ generally referred to as the "prior art."⁽⁴⁸⁾ Claims are normally drafted to strike a balance between the inventors technological contribution and the prior art.⁽⁴⁹⁾ Often, when claims are drafted strictly to encompass the work actually done by the inventor, however, claims result that are valid but too narrow to effectively exclude others from using variations of the invention, which incorporate minor alterations.⁽⁵⁰⁾ Alternatively, it is often difficult to obtain claims that closely approximate the prior art;⁽⁵¹⁾ however, if valid, these claims are likely to be more effective than narrow claims in excluding others from using the invention with minor variations.⁽⁵²⁾ Further, because an inventor may not claim more than he or she has invented, the claims must be supported by the information disclosed in the specification.⁽⁵³⁾ Thus, claims are interpreted with reference to the patent's specification,⁽⁵⁴⁾ and a patent does not grant exclusive rights to the subject matter disclosed in the specification but not encompassed by the claims.⁽⁵⁵⁾

C.  Novel Patent Issues Posed by the Biological Sciences

Technological advances in the biological sciences have led to the development of techniques for genetically modifying living organisms, as well as for the production of useful biological products.⁽⁵⁶⁾ As a result of this rapid technological advancement, the biological sciences have recently posed a number of novel issues with regard to both patentability standards,⁽⁵⁷⁾ and the scope of patent protection after patent issuance.⁽⁵⁸⁾ Several of these issues involve the patentability of living materials.⁽⁵⁹⁾ For example, the United States Supreme Court, in Diamond v. Chakrabarty,⁽⁶⁰⁾ decided the issue of whether a live, human-made micro-organism was patentable as a "manufacture"⁽⁶¹⁾ or "composition or matter"⁽⁶²⁾ under 35 U.S.C. § 101.⁽⁶³⁾ The organism at issue was a genetically engineered bacterium capable of digesting numerous components of crude oil and intended for use in the treatment of oil spills.⁽⁶⁴⁾ The Court held that this bacterium constituted patentable subject matter under § 101 because it was created by the inventor and had characteristics that distinguished it from any organisms found in nature.⁽⁶⁵⁾

One issue left unaddressed by Chakrabarty was whether non-naturally occurring, human-made, non-human animals constituted patentable subject matter under 35 U.S.C. § 101. This issue was addressed in 1987 by Assistant Secretary and Commissioner of Patents and Trademarks Donald J. Quigg in a public letter indicating that henceforth the PTO would consider non-human animals patentable subject matter.⁽⁶⁶⁾ The first patent claiming a non-human transgenic animal issued the following year.⁽⁶⁷⁾ In 1991, the Federal Circuit affirmed a district court holding that parties seeking to protect animals lacked standing to challenge the Commissioner's decision.⁽⁶⁸⁾

One particularly difficult issue presented by biotechnological inventions has been the satisfaction of the enablement requirement.⁽⁶⁹⁾ As described briefly above, the specification must disclose enough information "to enable any person skilled in the art . . . to make and use the [invention]"⁽⁷⁰⁾ without "undue experimentation."⁽⁷¹⁾ As a result of the undue experimentation standard, the requisite disclosure needed to satisfy the enablement requirement varies with several factors, including the predictability of the art and "the breadth of the claims."⁽⁷²⁾ While the necessity of some experimentation will not automatically preclude satisfaction of the enablement requirement, whether the enablement requirement is satisfied is determined by whether the disclosed information enables one skilled in the art to practice the invention without undue experimentation.⁽⁷³⁾ This is often a difficult standard to meet when the invention comprises biological materials that are difficult to reproduce, such as cell strains.⁽⁷⁴⁾ In many instances, the enablement requirement is most readily met by the deposition of a sample of the subject cell strain, or other biological materials, with a depository that guarantees public accessibility.⁽⁷⁵⁾

This Note reviews aspects of several recent decisions in which the Federal Circuit has interpreted patents for biotechnological inventions⁽⁷⁶⁾ and some of the practical implications of these decisions.⁽⁷⁷⁾ A further purpose of this Note is to suggest techniques that may assist in obtaining broad interpretation of patents claiming genetically engineered inventions.⁽⁷⁸⁾

  Patent Infringement and Claim Interpretation

A.  Patent Claims May Be Infringed Literally or Under the Doctrine of Equivalents

A determination of whether a patent has been infringed by an accused device⁽⁷⁹⁾ is a two-step analysis.⁽⁸⁰⁾ The first step is to interpret the claim at issue "to determine its proper scope and meaning,"⁽⁸¹⁾ followed by a determination of whether the accused device falls within that scope.⁽⁸²⁾ The former is an issue of law while the latter is a question of fact.⁽⁸³⁾

According to the landmark decision of Graver Tank & Manufacturing Co. v. Linde Air Products Co.,⁽⁸⁴⁾ an accused device can fall under the scope of the claim either literally or by being the equivalent of the patented invention.⁽⁸⁵⁾ This second method of determining whether an accused device infringes a patent claim is referred to as infringement under the "doctrine of equivalents."⁽⁸⁶⁾ In Graver Tank, the United States Supreme Court stated that infringement under the doctrine of equivalents may be found when an accused device "`performs substantially the same function in substantially the same way to obtain the same result'" as the claimed device.⁽⁸⁷⁾ For a finding of infringement, the accused device must possess every limitation of the patent claim at issue, or the substantial equivalent.⁽⁸⁸⁾ Because literal infringement of patent claims is rare,⁽⁸⁹⁾ courts are often left with the option of either holding that the accused device does not infringe the claim at issue or, under certain circumstances, determining whether the accused device infringes that claim under the doctrine of equivalents.⁽⁹⁰⁾

The doctrine of equivalents is an equitable doctrine applicable only when literal infringement is not found,⁽⁹¹⁾ and is intended to prevent an "unscrupulous copyist" from making insignificant changes in a patented invention to avoid infringement.⁽⁹²⁾ The doctrine of equivalents, however, does not always prevent one from intentionally designing around a patent's claims,⁽⁹³⁾ but design differences between the accused and patented devices must be substantial to avoid infringement.⁽⁹⁴⁾ The doctrine of equivalents is thus intended to prevent "a fraud on a patent"⁽⁹⁵⁾ while allowing for the development of new inventions with substantial improvements over patented inventions.⁽⁹⁶⁾

1.  Limitations on Claim Construction

When determining whether infringement of a patents claims has occurred, the court must begin by "determining the meaning and scope of the patent claims asserted to be infringed."⁽⁹⁷⁾ This construction is subject to several considerations in addition to the plain language of the claims.⁽⁹⁸⁾ For example, because a patents claims define the invention,⁽⁹⁹⁾ the doctrine of equivalents may not be used to rewrite those claims to encompass subject matter not originally intended by the patentee or the PTO examiner.⁽¹⁰⁰⁾ As a result, the patentee "must be content with protection on what he invented."⁽¹⁰¹⁾ Thus, while the doctrine of equivalents, as an equitable doctrine, is intended "to relieve an inventor from a semantic straight jacket when equity requires,"⁽¹⁰²⁾ it is not intended to permit judicial rewriting of claims so as to encompass non-equivalent devices.⁽¹⁰³⁾

The goal is to reach a balance between providing notice to the public as to the scope of the patent,⁽¹⁰⁴⁾ and thus what constitutes infringement, and protection of the patentee's legitimate property interests.⁽¹⁰⁵⁾ In many instances, holding that a patent encompasses only the subject matter literally defined by the claims would turn "the patent grant into a hollow and useless thing."⁽¹⁰⁶⁾ However, competing policy considerations,⁽¹⁰⁷⁾ and the fact that patents are reviewed by a governmental agency before issuance,⁽¹⁰⁸⁾ have resulted in a series of limitations being placed on the permissible constructions of claims.⁽¹⁰⁹⁾ These limitations generally focus on the prosecution process⁽¹¹⁰⁾ and whether claims encompassing an accused device would have been patentable in view of the prior art.⁽¹¹¹⁾

a.  Prosecution History Estoppel

One limitation on the construction of claims is that the patentee does not have property rights to subject matter surrendered during prosecution.⁽¹¹²⁾ The prosecution history of a patent is not only relevant for preventing a patentee from using the doctrine of equivalents to regain subject matter surrendered during prosecution, but is also used to determine the limits of claims when determining whether literal infringement has occurred.⁽¹¹³⁾ This results from the fact that claims are interpreted in light of their prosecution history.⁽¹¹⁴⁾ Thus, when an examiner rejects a claim, the applicant is presented with the option of either appealing the rejection of that claim, or amending the claim in accordance with the examiner's requirements and surrendering the subject matter of the dispute.⁽¹¹⁵⁾

Prosecution history estoppel, however, does not preclude application of the doctrine of equivalents in all instances in which the patent applicant has amended claims during prosecution.⁽¹¹⁶⁾ Claims are denied and amended for a variety of reasons.⁽¹¹⁷⁾ To determine the limiting effect of an amendment, it is necessary for the court to examine the "nature and purpose" of that amendment.⁽¹¹⁸⁾ Further, factual questions pertaining to the prosecution history may be addressed to assess the scope of the estoppel.⁽¹¹⁹⁾ Thus, claim construction is limited by prosecution history estoppel in that the patentee will be estopped from gaining in litigation only that subject matter which he surrendered during prosecution.

b.  Prior Art

A patent's claims may not be construed to encompass subject matter that was not patentable in view of the prior art when the application was filed.⁽¹²⁰⁾ As a result, because one may not patent subject matter that is barred by the prior art,⁽¹²¹⁾ the relevant prior art constrains the allowable range of equivalents that will be afforded a patents claims.⁽¹²²⁾ Conversely, inventions that represent dramatic technological advancements are given a greater range of equivalents than those that represent modification of existing inventions.⁽¹²³⁾

In Wilson Sporting Goods Co. v. David Geoffrey & Associates,⁽¹²⁴⁾ the Federal Circuit presented a test for determining whether the prior art prevents the allowable range of equivalents from encompassing the accused device.⁽¹²⁵⁾ The Wilson Sporting Goods court formulated the following test:

[A] hypothetical patent claim, sufficient in scope to literally cover the accused product[, is visualized]. The pertinent question then becomes whether that hypothetical claim could have been allowed by the PTO over the prior art. If not, then it would be improper to permit the patentee to obtain that coverage in an infringement suit under the doctrine of equivalents. If the hypothetical claim could have been allowed, then prior art is not a bar to infringement under the doctrine of equivalents.⁽¹²⁶⁾

Thus, the scope of a patent's claims may not encompass what has been committed to the public domain by the prior art.⁽¹²⁷⁾

In Wilson Sporting Goods, the court held that a hypothetical claim that encompassed the alleged infringing device would be so similar to the prior art "that the hypothetical claim . . . viewed as a whole would have been obvious."⁽¹²⁸⁾ The same conclusion, however, did not necessarily apply to dependent claims.⁽¹²⁹⁾ Because dependent claims are generally narrower in scope than the independent claims to which they refer, "it does not automatically follow that the ranges of equivalents of these narrower claims would encompass the prior art, because of their added limitations."⁽¹³⁰⁾

The Federal Circuit has made clear that the hypothetical claim analysis of Wilson Sporting Goods has no bearing on the validity of a patent's claims because the only issue to be determined is whether an expanded claim encompassing the accused device would have been patentable in view of the prior art.⁽¹³¹⁾ This approach results in a patentability analysis to determine only the validity of a hypothetical claim that encompasses the accused device based on the attributes of that accused device, the relevant prior art, and the patent claim at issue.⁽¹³²⁾

One issue left unaddressed in Wilson Sporting Goods was whether a full-fledged patentability study is necessary whenever prior art potentially limits the scope of the doctrine of equivalents.⁽¹³³⁾ This issue was partly addressed in International Visual Corp. v. Crown Metal Manufacturing,⁽¹³⁴⁾ a case in which the Federal Circuit noted that the hypothetical claim analysis is only one method for determining whether the doctrine of equivalents is limited by the prior art.⁽¹³⁵⁾ The court stated that the hypothetical claim analysis is just one "way of expressing the well-established principle `that a patentee should not be able to obtain, under the doctrine of equivalents, coverage which he could not lawfully have obtained from the PTO by literal claims.'"⁽¹³⁶⁾ Thus, lower courts are free to apply the hypothetical claim analysis when it aids in the determination of the range of equivalents claims are to be given;⁽¹³⁷⁾ however, the scope of the inquiry remains an open question.⁽¹³⁸⁾

c.  Subject Matter Not Considered by the Examiner During Prosecution

A third, and arguably quite recent, limitation on the construction of claims is that claims are not to be construed to encompass subject matter not considered by the PTO during prosecution.⁽¹³⁹⁾ This limitation appears to apply regardless of whether the applicant inadvertently⁽¹⁴⁰⁾ or deliberately⁽¹⁴¹⁾ narrowed the scope of examination. As a result, claim construction is limited in situations in which the patent applicant has "neither described nor enabled" the subject matter in the patent specification,⁽¹⁴²⁾ or when the specification contains subject matter "upon which the PTO could not reasonably have relied when it issued the patent."⁽¹⁴³⁾

This limitation on claim construction appears to have been first applied in North American Vaccine, Inc. v. American Cyanamid Co.,⁽¹⁴⁴⁾ a case in which the court addressed whether a vaccine produced by the defendant, American Cyanamid Co., infringed claims of a patent issued to the plaintiff, the National Research Council of Canada (NRC).⁽¹⁴⁵⁾ The patent at issue⁽¹⁴⁶⁾ claimed antigenic polysaccharide: protein conjugates consisting of a polysaccharide molecule with a protein molecule attached "`to a terminal portion of the polysaccharide without significant crosslinking,'"⁽¹⁴⁷⁾ a method of producing such a conjugate, and the use of that conjugate as a vaccine.⁽¹⁴⁸⁾ While the defendant's allegedly infringing vaccine contained polysaccharide molecules with proteins attached to one end, both ends, and to other portions of the polysaccharide,⁽¹⁴⁹⁾ the issue presented to the Federal Circuit was whether the claims literally encompassed vaccines in which protein molecules were linked at more than one location on those polysaccharide molecules.⁽¹⁵⁰⁾

In determining whether the claims at issue were infringed, the court focused on the issue of whether the phrase "`a terminal portion'" in claim eleven of the NRC's patent referred to proteins linked to only one or to both terminal ends of the polysaccharide molecules.<sup>(151)</sup> The court noted that while the indefinite article "A," when used in a patent, may be interpreted to refer to more than one element,<sup>(152)</sup> there was nothing in the patent specification to indicate that "A" was intended "to have other than its normal singular meaning."<sup>(153)</sup> First, the court noted that all references to linkages in the specification referred to "a linkage, not multiple linkages."<sup>(154)</sup> Also, the examples provided in the specification taught how to produce conjugates likely to have proteins attached to a single terminal end of the polysaccharide molecules.<sup>(155)</sup> Further, the court noted that claim eleven referred to the linkage of protein to the polysaccharide molecules without "`significant crosslinking,'"⁽¹⁵⁶⁾ and the patent specified that the crosslinking to be avoided was not between the polysaccharide molecules, but "at more than one terminal."⁽¹⁵⁷⁾ In response, NRC argued that the "`significant crosslinking' that the inventors intended to avoid was not end-to-end crosslinking, but crosslinking across the backbone of the polysaccharide molecule."<sup>(158)</sup> The Federal Circuit rejected this argument by noting that "[t]here is no such disclosure of the concept of avoiding crosslinking along the backbone in this patent. Thus, an invention of that breadth does not meet the description requirement."<sup>(159)</sup> As a result, the court interpreted the phrase "`a terminal portion'" to mean polysaccharide molecules with protein attached to only a single terminus.⁽¹⁶⁰⁾

The North American Vaccine court interpreted claim eleven strictly as disclosed in the patent specification,⁽¹⁶¹⁾ and the issue of whether the accused vaccine infringed the claims at issue was determined solely by whether the components of the defendant's vaccine containing protein molecules linked to more than one location on the polysaccharide molecules fell within the literal scope of those claims.⁽¹⁶²⁾ The court held that there was no infringement of the claims at issue because the specification referred to the linkage of protein to only one end of the polysaccharide molecules,⁽¹⁶³⁾ while the defendant's vaccine contained a mixture of conjugates wherein protein molecules were conjugated to one end, both ends, and other sites on the polysaccharide molecules.⁽¹⁶⁴⁾ Thus, while claim eleven was not held to be invalid, it did not encompass the accused vaccine because the specification "neither described nor enabled" such a reading.⁽¹⁶⁵⁾

In summary, the patent at issue in North American Vaccine failed to encompass the accused vaccine because it described only polysaccharide molecules with proteins attached to one terminus,⁽¹⁶⁶⁾ and described methods intended to produce a vaccine containing only such molecules.⁽¹⁶⁷⁾ The failure of the applicant to describe or to enable for the production of polysaccharide molecules with proteins attached at multiple locations resulted in such molecules being excluded from the scope of the patent.⁽¹⁶⁸⁾ Thus, under the reasoning applied by the Federal Circuit in North American Vaccine, when an applicant describes an invention narrowly, claims will not be interpreted so as to encompass subject matter other than that adequately disclosed in the specification.⁽¹⁶⁹⁾

In Genentech, Inc. v. Wellcome Foundation Ltd.,⁽¹⁷⁰⁾ one problem that faced the Federal Circuit was how to interpret a patent specification in which the applicant included several definitions for the same key term in the claims.⁽¹⁷¹⁾ The court believed that at least four different conflicting definitions were presented for the term, "human tissue plasminogen activator [t-PA]."⁽¹⁷²⁾ In response to the multitude of potential definitions provided in the patent specification, the court stated that "[t]hese diverse definitions reflect either inartful drafting, a conscious attempt to create ambiguity about the scope of the claims, or a desire to claim a wide variety of materials not described or enabled in the specification."⁽¹⁷³⁾ The court decided that "[a]n appropriate method for resolving the issue"⁽¹⁷⁴⁾ was "to avoid those definitions upon which the PTO could not reasonably have relied when it issued the patent."⁽¹⁷⁵⁾ The Federal Circuit, citing North American Vaccine, concluded that this approach was appropriate to prevent applicants from consciously obtaining a broader scope of property rights than was examined by the PTO during prosecution.⁽¹⁷⁶⁾ The court believed that the PTO could not have relied on three of the four definitions presented in the specifications because they encompassed an infinite number of molecules for which enablement had not been provided.⁽¹⁷⁷⁾ As a result, the Federal Circuit determined that the phrase "`human tissue plasminogen activator'" meant natural t-PA--the product of the human DNA sequence encoding that protein.⁽¹⁷⁸⁾

The definitions cited by the court were presented at the beginning of the Detailed Description of the patent,⁽¹⁷⁹⁾ in which the applicant appears to have been attempting to describe t-PA with respect to its known structural and functional properties.⁽¹⁸⁰⁾ While some of the definitions provided in the specification encompassed subject matter for which there was no enabling disclosure,⁽¹⁸¹⁾ the applicant apparently was attempting to provide the most complete description of the relevant subject matter possible at the time the original application was filed.⁽¹⁸²⁾ Arguably, the applicant was merely attempting to provide an adequate description of the subject matter sufficient to support the patent's claims based on the information available as of the filing date.⁽¹⁸³⁾

While the Federal Circuit purported to select a narrow structural definition of t-PA from those provided by the applicant,⁽¹⁸⁴⁾ the court, in effect, turned the disclosure against the applicant by holding that the phrase "human tissue plasminogen activator" included all of the disclosed properties read as a whole when determining whether, under the doctrine of equivalents, the accused product was equivalent to the claimed invention.⁽¹⁸⁵⁾ Thus, the court used an "operative definition for purposes of equivalency analysis" that reflected "the intended function as seen in the context of the patent, the prosecution history, and the prior art."⁽¹⁸⁶⁾ Such a definition, instead of being subject to expansive interpretation, effectively placed a series of successive limitations on the claimed subject matter based on the disclosed functional properties of natural t-PA.⁽¹⁸⁷⁾

The limitations on claim interpretation espoused in North American Vaccine and Genentech⁽¹⁸⁸⁾ place applicants in the difficult position of deciding whether to describe their inventions in the form of a single embodiment or in detail from varying perspectives. In one instance, the applicant may be denied the benefit of broad claim interpretation during litigation because either the subject matter was "neither described nor enabled."⁽¹⁸⁹⁾ In the other, the subject matter may be held to have been described in a manner "upon which the PTO could not reasonably have relied when it issued the patent."⁽¹⁹⁰⁾ Thus, under the reasoning of North American Vaccine and Genentech, applicants are presented with the choice of describing their inventions in limited detail and losing property rights to devices that are "neither described nor enabled,"⁽¹⁹¹⁾ or describing their inventions from varying perspectives and running the risk of having their patents' claims interpreted narrowly in the course of litigation.⁽¹⁹²⁾

2.  Genentech, Inc. v. Wellcome Foundation Ltd.:⁽¹⁹³⁾ An Application of the Doctrine of Equivalents in Infringement    Litigation Involving Patents Claiming Genetically Engineered   Inventions⁽¹⁹⁴⁾

As yet, the Federal Circuit has not directly addressed the application of the doctrine of equivalents to alleged infringement resulting from nucleic acid sequences containing minor modifications as compared to a patented sequence. In Genentech, however, the court came close to addressing such an issue.⁽¹⁹⁵⁾ In Genentech, the Federal Circuit determined whether a modified protein produced by genetic engineering infringed any of three patents claiming a human protein as extracted from cancer cells⁽¹⁹⁶⁾ (`603 patent), the DNA sequence encoding that human protein<sup>(197)</sup> (`075 patent), and the process of producing that protein from a DNA sequence⁽¹⁹⁸⁾ (`330 patent).⁽¹⁹⁹⁾

The three patents at issue⁽²⁰⁰⁾ were either owned by or licensed to the plaintiffs, Genentech, Inc., Innovi N.V., and Leuven Research and Development VZW.⁽²⁰¹⁾ The owners/licensees initially brought an infringement action alleging that two products--met-t-PA and FE1X⁽²⁰²⁾--infringed their patents claiming natural t-PA.⁽²⁰³⁾ These products were produced by the defendants--the Wellcome Foundation Ltd. and Genetics Institute.⁽²⁰⁴⁾

One issue addressed by the Genentech court was "whether the jury's implied conclusion--that the specific activity limitation appearing in the `603 [patent] claims was met by FE1X either literally or [under the doctrine of equivalents]--[was] supported by substantial evidence."<sup>(205)</sup> The court noted that the specific activity limitation in the claims of the `603 patent was added during prosecution, to distinguish the invention from the prior art,⁽²⁰⁶⁾ and that the specific activity of FE1X was closer to the prior art than the activity enumerated in the claims.⁽²⁰⁷⁾ As a result, the Federal Circuit held that prosecution history estoppel placed FE1X outside the range of equivalents,⁽²⁰⁸⁾ and, thus, FE1X did not infringe the claims of the `603 patent under the doctrine of equivalents and "[n]o reasonable jury could have concluded otherwise."⁽²⁰⁹⁾

As already noted,⁽²¹⁰⁾ another issue that the court faced was "the meaning of the phrase `human tissue plasminogen activator' appearing in the `075 and `330 claims."⁽²¹¹⁾ While an applicant is normally allowed to be his own lexicographer and, thus, may define the terms used in the application,⁽²¹²⁾ the court felt that the patents at issue contained at least four conflicting definitions of t-PA.⁽²¹³⁾ The Federal Circuit determined that, of those definitions provided by the applicant, a narrow structural definition was the appropriate one because it was the one most consistent with the claims, and because the others were "hopelessly overbroad."⁽²¹⁴⁾ The definition of t-PA chosen for interpretation of the claims was "t-PA produced through recombinant DNA technology but having the same structure as natural t-PA."⁽²¹⁵⁾ Thus, the phrase "natural t-PA" was interpreted as referring to t-PA molecules structurally identical to human t-PA and possibly naturally occurring variants.⁽²¹⁶⁾

After deciding upon an appropriate definition for t-PA, the court determined the issue of whether the record contained sufficient evidence "to support the jury's implied conclusion that the `human tissue plasminogen activator' limitation appearing in the `075 and `330 claims is met by FE1X."<sup>(217)</sup> The court noted that FE1X does not literally meet this limitation because "it is not natural t-PA" and then considered the issue of infringement under the doctrine of equivalents.<sup>(218)</sup> The court then held that, under the Graver Tank test,<sup>(219)</sup> FE1X was not shown to be the equivalent of natural t-PA because the "function" prong of the test had not been met.<sup>(220)</sup> In reaching this conclusion, the court compared FE1X with natural t-PA from a functional perspective.<sup>(221)</sup> First, the specifications indicated that the ability to bind fibrin was required for the function of t-PA.<sup>(222)</sup> Also, according to the court, fibrin binding ability distinguishes natural t-PA from the prior art.<sup>(223)</sup> The affinity of FE1X for fibrin, however, is less than one half that of natural t-PA.<sup>(224)</sup> The court further noted that a specific amino acid and two functional domains<sup>(225)</sup> believed to be crucial to the function of t-PA are not present in FE1X.<sup>(226)</sup> Finally, FE1X has an in vivo half-life<sup>(227)</sup> approximately ten times that of t-PA.<sup>(228)</sup> Thus, the court concluded that FE1X infringed claims of neither the `075 and `330 patents because the owners/licensees failed to establish that FE1X functions in the same way as natural t-PA.⁽²²⁹⁾

The reasoning applied by the Federal Circuit when determining that FE1X did not infringe patents claiming human tissue plasminogen activator will potentially have wide ranging effects on intellectual property rights in genetically engineered inventions.⁽²³⁰⁾ This conclusion is based on the fact that the court held that FE1X does not infringe the claims of the `075 and `330 patents because FE1X differs both structurally⁽²³¹⁾ and functionally⁽²³²⁾ from natural t-PA, and often, proteins are claimed as comprising single inventions,⁽²³³⁾ even though proteins are composed of more than one functional domain.⁽²³⁴⁾ Further, each functional domain of a protein may have different functional properties.⁽²³⁵⁾ Technology has recently been developed that enables the generation of novel hybrid proteins by the fusion of functional domains and even of entire proteins.⁽²³⁶⁾

Under the Genentech reasoning,⁽²³⁷⁾ a hybrid protein consisting of functional domains derived from a patented protein will not infringe claims for the natural full-length protein as long as the final product has functional properties that distinguish it from its patented counterpart.⁽²³⁸⁾ Additionally, in many instances, a non-infringing product could be produced by modification of a claimed protein resulting in the alteration of that protein's functional properties.⁽²³⁹⁾ One example of such a modification would be the deletion of domains not required for a particular desired functional activity. Whether this type of a modification results in a non-infringing product would presumably be determined by whether the specification indicated that the deleted portion was necessary for the functional activity of interest.⁽²⁴⁰⁾ Thus, in many such instances, under the reasoning of Genentech, a recombinant product could avoid infringement both literally and under the doctrine of equivalents by being structurally and functionally distinct from its patented counterpart.⁽²⁴¹⁾

Competing policy considerations create a conflict between protecting the legitimate property rights of patentees from inventions embodying minor variations resulting from technological advancement,⁽²⁴²⁾ the requirements of 35 U.S.C. § 112, paragraph one,⁽²⁴³⁾ and the Constitutional mandate of "promot[ing] the Progress of Science and useful arts."⁽²⁴⁴⁾ Strict adherence to the reasoning and holding of Genentech, with respect to the analysis employed by the Federal Circuit when determining that FE1X did not infringe the claims of the `075 and `330 patents, is arguably inconsistent with the policy of protecting patented inventions from unforeseen technological developments.⁽²⁴⁵⁾ While the specification "must teach those skilled in the art how to make and use the full scope of the claimed invention without `undue experimentation,'"⁽²⁴⁶⁾ claimed inventions generally are not limited by the specific embodiments presented in the specification, and infringement under the doctrine of equivalents is determined by whether the accused device is the equivalent of the invention as claimed.⁽²⁴⁷⁾

Policy considerations presumably weighed by the Federal Circuit in Genentech, were the balancing of the property rights granted to protect the actual invention encompassed by the patent,⁽²⁴⁸⁾ and the encouraging of future inventors to develop new inventions.⁽²⁴⁹⁾ If patents claiming proteins are viewed as encompassing each of the individual domains of which they are comprised, issues would then presumably arise as to whom has property rights in those domains. For example, because domains with similar functions and amino acid sequences are often found in numerous proteins⁽²⁵⁰⁾ when a specific domain is present in more than one claimed protein, conflicts would presumably arise over which party has exclusive rights to that domain. Further, if patents are held to encompass each functional domain of claimed proteins, there would be little room for future inventors to develop new inventions by recombination of those domains.⁽²⁵¹⁾ In view of this, the Genentech holding appears to stand essentially for the established proposition that patents only encompass that which is actually invented by the patentees.⁽²⁵²⁾ Thus, it appears that "substantial" modification of a claimed genetically engineered invention will result in a new non-infringing product.⁽²⁵³⁾

Genentech left unaddressed the issue of whether claims encompassing a protein may be infringed under the doctrine of equivalents by a modified form of the same protein containing a single amino acid alteration. While the district court held that both met-t-PA and FE1X infringed the patents at issue under the doctrine of equivalents,⁽²⁵⁴⁾ the Federal Circuit was only presented with the issue of whether the claims at issue were infringed by FE1X.⁽²⁵⁵⁾ Unlike FE1X, met-t-PA is identical to natural t-PA with the exception of a single amino acid substitution.⁽²⁵⁶⁾ However, the sale of met-t-PA was discontinued, and the manufacturer withdrew from the litigation after the district court decision.⁽²⁵⁷⁾

It is very likely that the Federal Circuit would have held that met-t-PA infringed claims of all of the patents at issue under the doctrine of equivalents.⁽²⁵⁸⁾ This conclusion is based on the fact that the single amino acid substitution of met-t-PA apparently did not significantly alter the functional properties of the protein.⁽²⁵⁹⁾ Because met-t-PA is not natural t-PA,⁽²⁶⁰⁾ literal infringement of the claims at issue by met-t-PA would not have been found;⁽²⁶¹⁾ however, met-t-PA presumably would have been held to perform "`substantially the same function in substantially the same way to obtain the same result'"⁽²⁶²⁾ as natural t-PA.

Due to rapid advancements in molecular biology, and because minor modification of genetically engineered inventions will result in products that generally will not fall within the literal scope of claims for a single nucleic or amino acid sequences,⁽²⁶³⁾ these claims are heavily dependent on the doctrine of equivalents.⁽²⁶⁴⁾ As a result, patents claiming genetically engineered inventions may be of little value when this doctrine is inapplicable.⁽²⁶⁵⁾

3.  Coping with Limitations on the Doctrine of Equivalents for Patents Claiming Genetically Engineered Inventions

Because literal infringement is rare,⁽²⁶⁶⁾ limitations on the allowable range of equivalents resulting from the applicant's disclosure and the prosecution process will often affect the scope of property rights conferred by the patent.⁽²⁶⁷⁾ These limitations can be dealt with in several ways.⁽²⁶⁸⁾ First, in some instances it may be possible to draft claims broadly to avoid reliance on this doctrine.⁽²⁶⁹⁾ This approach is limited by the breadth of claims allowed by the PTO and not held invalid during infringement litigation⁽²⁷⁰⁾ and the ease with which one may design around the invention as literally claimed. Because applicability of the doctrine of equivalents is limited when an accused device comprises subject matter in the prior art, "surrendered" during prosecution, or not considered by the PTO examiner,⁽²⁷¹⁾ the outcome of an infringement action may turn on whether the accused product infringes the claim or claims at issue either literally or under a narrow range of equivalents.⁽²⁷²⁾ It may be advantageous, therefore, to draft claims broadly to avoid reliance on the doctrine of equivalents. One example of a broad claim for a genetically engineered invention is a generic claim that encompasses all nucleic acid sequences encoding a specific amino acid sequence.⁽²⁷³⁾ It is also necessary, however, to draft the patent specification to provide sufficient written description and enablement to allow for broad literal interpretations.⁽²⁷⁴⁾

A second, and presumably in many instances a more practical, approach is to avoid the various limitations on the doctrine of equivalents.⁽²⁷⁵⁾ This, however, presents the applicant with a choice between two equally undesirable alternatives. For example, if the applicant negotiates an issue with the examiner and surrenders subject matter, that subject matter will not be encompassed by the patent.⁽²⁷⁶⁾ Alternatively, if subject matter is not "examined" during prosecution, that subject matter is susceptible to the criticism that it was not considered by the examiner during prosecution and thus is not encompassed by the claims.⁽²⁷⁷⁾ Further, if the disclosure does not encompass multiple variations of the invention, the applicant runs the risk of the claims not encompassing that subject matter because it was "neither described nor enabled."⁽²⁷⁸⁾ In effect, a detailed disclosure designed to describe the subject invention in sufficient detail to defeat the inadequate disclosure limitation described in North American Vaccine,⁽²⁷⁹⁾ may be so detailed that it is not fully reviewed at the PTO and is thus susceptible to the argument that the invention should be limited to subject matter reasonably relied upon by the PTO when it issued the patent.⁽²⁸⁰⁾

A separate problem faces applicants claiming inventions comprising full-length proteins as single inventions, because the use of functional domains of those proteins will apparently not infringe those claims.⁽²⁸¹⁾ One method of dealing with this situation is, where possible, to claim the individual functional domains of proteins. This tactic, however, will be of limited use for two reasons. First, in many instances domains are identified by comparison of their amino acid sequence with proteins of known function that are in the prior art.⁽²⁸²⁾ As a result, many structural and functional domains of proteins are not patentable in view of the prior art.⁽²⁸³⁾

Second, often regions of proteins are not known to perform a specific function until some time after they have been identified.⁽²⁸⁴⁾ This results from the fact that extensive experimentation is often required to identify functional activities of such regions.⁽²⁸⁵⁾ Thus, applicants, who are often scientists under pressure to publish results,⁽²⁸⁶⁾ may create their own prior art bars to patentability by publishing data before functional activities have been identified.

B.  Generic Claims⁽²⁸⁷⁾ for Genetically Engineered Inventions

Applicants seeking patents claiming genetically engineered inventions have sought generic claims in attempts to generate broad patent rights in their inventions.⁽²⁸⁸⁾ Because a finding of literal infringement "requires that each limitation in the asserted claims be present in the accused device,"⁽²⁸⁹⁾ claims for a specified DNA sequence, for example, will not be literally infringed by a DNA sequence that is even just slightly altered.⁽²⁹⁰⁾ Due to degeneracy of the genetic code,⁽²⁹¹⁾ a considerable number of different DNA sequences can encode a protein identical to the product of a natural DNA sequence.⁽²⁹²⁾ Alternatively, an altered DNA sequence can encode a slightly altered form of the protein encoded by the claimed DNA sequence but having identical functional properties.⁽²⁹³⁾ In each of these instances there would be no literal infringement of claims that strictly encompass the natural DNA sequence.⁽²⁹⁴⁾ Thus, when DNA or amino acid sequences are strictly claimed, an infringement action would, by necessity, rely on the doctrine of equivalents.

1.  Generic Claims and the Requirements of 35 U.S.C. § 112

A patent must "conclude with one or more claims particularly pointing out and distinctly claiming the subject matter that the applicant regards as his invention."⁽²⁹⁵⁾ Thus, because claims define the subject invention,⁽²⁹⁶⁾ they must be definite enough to explain the invention to one skilled in the art.⁽²⁹⁷⁾ While a claim need not describe "all species that claim encompasses,"⁽²⁹⁸⁾ it must be supported by a written disclosure that enables one skilled in the relevant art to make and use the invention.⁽²⁹⁹⁾ Generic claims can be supported, however, by a disclosure which requires some experimentation to practice the invention, "unless the amount of experimentation is unduly extensive."⁽³⁰⁰⁾ The emphasis is not on whether experimentation is required but on whether that experimentation is unduly excessive.⁽³⁰¹⁾ As a result, it is not always necessary to disclose all species that a claim encompasses.⁽³⁰²⁾

The adequacy of a disclosure for meeting the enabling requirement of 35 U.S.C. § 112 varies with a number of factors including the predictability of the art and the breadth of the claims.⁽³⁰³⁾ In general, the stringency of the enablement requirement increases with the unpredictability of the art.⁽³⁰⁴⁾ However, even in an unpredictable art, "applicants are not required to disclose every species encompassed by their claims,"⁽³⁰⁵⁾ but the disclosure must be sufficient to teach one skilled in the art "how to make and . . . use the invention as broadly as it is claimed."⁽³⁰⁶⁾

The enablement requirement, however, is not the only disclosure hurdle that an applicant faces.⁽³⁰⁷⁾ The applicant must also satisfy the written description requirement.⁽³⁰⁸⁾ While an applicant need not disclose every embodiment of the invention,⁽³⁰⁹⁾ satisfaction of the written description requirement demands that the applicant describe the invention in sufficient detail that persons of ordinary skill in the art will recognize that the applicant was in possession of an invention with the claimed characteristics at the time the application was filed.⁽³¹⁰⁾ Thus, the applicant must show that he or she had possession of the invention as claimed when the application was filed.⁽³¹¹⁾

2.  The Federal Circuit and Generic Claims for Genetically Engineered Inventions

Claims for genetically engineered inventions can be generic in the sense that they claim genes capable of being expressed in evolutionary diverse organisms,⁽³¹²⁾ or they encompass multiple variant forms of one nucleic or amino acid sequence.⁽³¹³⁾

In Amgen, Inc. v. Chugai Pharmaceutical Co.,⁽³¹⁴⁾ the Federal Circuit affirmed a district court holding that a generic claim for DNA sequences encoding a protein and all variant DNA sequences encoding proteins with similar functional properties was invalid for lack of enablement.⁽³¹⁵⁾ The generic claim at issue, claim seven,⁽³¹⁶⁾ was written in a functional format and effectively claimed all DNA sequences encoding erythropoietin (EPO) and analogs with similar biological properties.⁽³¹⁷⁾ In effect, this claim encompassed all DNA sequences encoding functional analogs of EPO.⁽³¹⁸⁾ The Amgen court noted that over 3,600 EPO analogs could be made by replacement of a single amino acid, and over one million analogs could be made by replacement of three amino acids.⁽³¹⁹⁾ While noting that under some circumstances it might be possible for generic claims to nucleic acid sequences to be valid,⁽³²⁰⁾ in this particular instance, the enablement requirement for generating all of these analogs had not been satisfied.⁽³²¹⁾ Thus, claim seven was invalid for lack of enablement because it encompassed all DNA sequences encoding proteins with EPO-like activity while the applicant provided a disclosure "only of how to make EPO and a very few analogs."⁽³²²⁾

The Amgen court noted that while "it is not necessary for the patent applicant to test all the embodiments of his invention,"⁽³²³⁾ the applicant must "provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims. For DNA sequences, this means disclosing how to make and use enough sequences to justify grant of the claims sought."⁽³²⁴⁾ The court held that Amgen had not met this standard because the patent specification did not contain a disclosure that enabled one skilled in the art to make and use the EPO analogs encompassed by claim seven.⁽³²⁵⁾

While the Amgen court affirmed the district court's decision that claim seven was invalid, the Federal Circuit indicated that generic claims to nucleic acid sequences could be valid when those claims "are of a scope appropriate to the invention disclosed by the applicant."⁽³²⁶⁾ Further, the court noted, the scope of the subject matter encompassed by "`the claims must bear a reasonable correlation to the scope of enablement provided.'"⁽³²⁷⁾ In order to meet the enablement requirement for claim seven, the applicant was required to disclose how to identify EPO analogs that fell within the scope of the claim, methods for making such analogs, and "structural requirements for producing compounds with EPO-like activity."⁽³²⁸⁾

Subsequent to Amgen, the court in In re Vaeck⁽³²⁹⁾ affirmed an examiner's rejection of generic claims to "[a] chimeric gene capable of being expressed in Cyanobacteria"⁽³³⁰⁾ encoding an insecticidally active protein because the disclosure failed to satisfy the enablement requirement for the expression of such genes in all of the organisms encompassed by the claims.⁽³³¹⁾ The applicant's claims encompassed the expression of the subject chimeric gene in all cyanobacteria while the disclosure provided working examples describing the construction of only a single strain of cyanobacteria expressing such a gene.⁽³³²⁾ The court noted that because cyanobacteria are "a diverse and relatively poorly understood group of microorganisms, the required level of disclosure will be greater than, for example, the disclosure of an invention involving a `predictable' factor such as a mechanical or electrical element."⁽³³³⁾

Fiers v. Revel⁽³³⁴⁾ involved a priority dispute between three applicants who filed applications claiming DNA sequences encoding human fibroblast beta-interferon.⁽³³⁵⁾ The Federal Circuit held that Revel's application failed to meet the written description requirement because the nucleotide sequence of the gene encoding beta-interferon was not disclosed,⁽³³⁶⁾ and stated that "[a]n adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself."⁽³³⁷⁾ The Federal Circuit further noted in Fiers that a "bare reference to a DNA" with a statement of how to isolate that molecule "is not a description; it does not indicate that Revel was in possession of the DNA."⁽³³⁸⁾

It is unclear at present whether an applicant, in order to satisfy the written description requirement, must show that he or she was in possession of every DNA sequence that a generic claim encompasses.⁽³³⁹⁾ Such an interpretation of Fiers would be in conflict with statements in Amgen that "generic claims to genetic sequences [may] be valid where they are of a scope appropriate to the invention disclosed by an applicant."⁽³⁴⁰⁾

3.  The PTO and the Issuance of Generic Claims for Genetically Engineered Inventions

Currently, generic claims that encompass multiple DNA or amino acid sequences are apparently allowed by the PTO when they are commensurate with the scope of the invention and an enabling disclosure has been provided.⁽³⁴¹⁾ In Ex parte Anderson,⁽³⁴²⁾ the Board of Patent Appeals and Interferences upheld an examiner's rejection of a generic claim, claim eighteen, which encompassed all variant DNA sequences encoding functional analogs of human interleukin-3⁽³⁴³⁾ with the amino acid proline at position eight in the polypeptide chain.⁽³⁴⁴⁾ While the claim was rejected on grounds other than failure to meet the enablement requirement, the Board noted that in Amgen a claim of similar scope was held invalid by the Federal Circuit for failure to meet the enablement requirement.⁽³⁴⁵⁾

While claim eighteen in Ex parte Anderson is arguably narrower in scope than claim seven in Amgen,⁽³⁴⁶⁾ the PTO has recently allowed generic claims of similar scope for several inventions comprising nucleic and amino acid sequences.⁽³⁴⁷⁾ The PTO appears to allow such claims when applicants demonstrate that a number of molecules function in a manner similar to those actually disclosed in the specification, and the applicant has met the enablement requirement for producing such molecules.⁽³⁴⁸⁾

In many instances, the enablement requirement for generic claims for genetically engineered inventions is met by the inclusion of methods for site-directed mutagenesis⁽³⁴⁹⁾ directed to the generation of the claimed variant molecules.⁽³⁵⁰⁾ Site-directed mutagenesis is a biochemical technique which enables one to specifically alter DNA sequences.⁽³⁵¹⁾ This technique allows, for example, one to alter a DNA sequence so that almost any amino acid in a protein can be replaced with any other amino acid.⁽³⁵²⁾

Another technique, referred to as combinatorial mutagenesis,⁽³⁵³⁾ can presumably also be used to meet the enablement requirement for some generic claims for genetically engineered inventions.⁽³⁵⁴⁾ This technique allows for the relatively simple production and screening of large numbers of randomly generated analogs of a protein for functional activity where either specific amino acids⁽³⁵⁵⁾ or entire regions of the original protein have been altered or replaced.⁽³⁵⁶⁾ While the enablement requirement for claims similar in scope to claim seven in Amgen⁽³⁵⁷⁾ probably cannot be met at this time, these techniques can be used to make a good faith argument that many generic claims for both nucleic and amino acid sequences can be supported by a disclosure sufficient to enable one skilled in the art to produce such sequences.

One example of a recently issued patent with generic claims for an amino acid sequence is U.S. Patent No. 5,350,836 entitled "Growth Hormone Antagonists" (`836 patent).<sup>(358)</sup> The invention of the `836 patent comprises modified growth hormones in which specific amino acids are either deleted or replaced with other amino acids resulting in growth hormone analogs capable of retarding the growth enhancing effects of the natural growth hormone.⁽³⁵⁹⁾ The enablement requirement for the generic claims in the `836 patent is presumably satisfied both by the inclusion of combinatorial mutagenic techniques in the patent specification⁽³⁶⁰⁾ and by an example describing the alteration of DNA sequences by site-directed mutagenesis.⁽³⁶¹⁾

The scope of the generic claims of the `836 patent appear to be commensurate with the scope of the invention because the inventors disclosed several amino acid residues for which alterations could result in growth hormone antagonizing activity,⁽³⁶²⁾ and actually made a number of functional variant hormones.⁽³⁶³⁾ Further, all of the variant proteins with functional activity as growth hormone antagonists were not known⁽³⁶⁴⁾ and it was presumably impractical to both make and screen all possible variants.⁽³⁶⁵⁾ This impracticality results from the fact that replacement of two different amino acids in the naturally occurring protein, with each of twenty amino acids, results in 399 possible recombinant molecules,⁽³⁶⁶⁾ and the functional assay for the growth retarding effects was the reduction in size of transgenic animals expressing the altered protein.⁽³⁶⁷⁾ Because the construction of transgenic animals is a labor intensive and time-consuming task,⁽³⁶⁸⁾ the problem here presumably was not with the generation of all the possible combinations of growth hormone antagonists, but with the screening of each of the molecules for functional activity.

4.  Generic Claims that Encompass All Nucleotide Sequences Encoding a Specific Amino Acid Sequence

While the issue of whether generic claims that encompass all DNA sequences encoding one amino acid sequence can be sufficiently supported by a patent disclosure to meet the requirements of 35 U.S.C. § 112 has not been directly addressed by the Federal Circuit, the court noted in In re Deuel⁽³⁶⁹⁾ that such claims were potentially invalid because the disclosure failed to satisfy the enablement requirement.⁽³⁷⁰⁾

Two of the claims at issue in In re Deuel encompassed all DNA sequences encoding human and bovine heparin-binding growth factors.⁽³⁷¹⁾ The issue of whether such claims were invalid for the failure to meet the requirements of 35 U.S.C. § 112 was not before the Federal Circuit; however, the court noted that those claims "may be considered inadequately supported by the disclosure of the application."⁽³⁷²⁾ While the enablement requirement can presumably be satisfied for generic claims encompassing all DNA sequences encoding a specific amino acid sequence, satisfaction of the written description requirement poses a potentially more difficult obstacle for applicants.

As already discussed, the enablement requirement is met when the disclosure provides sufficient information to enable one skilled in the relevant art to practice the invention without undue experimentation.⁽³⁷³⁾ One could presumably satisfy the enablement requirement for a claim encompassing all DNA sequences encoding a specific amino acid sequence by disclosing one such sequence and method for producing the degenerate DNA sequence encoding the same amino acid sequence.⁽³⁷⁴⁾ One example of a method for producing the remainder of the sequences would employ multiple rounds of site-directed mutagenesis using mis-matched degenerate oligonucleotide primers, as shown in Figure 1.⁽³⁷⁵⁾

In order to produce all DNA sequences that encode one amino acid sequence, it would be necessary to produce a population of DNA molecules in that nucleotides have been replaced such that all of the alternate codons that encode each amino acid in the subject protein are present in the final population. Because codons can vary at any of their three nucleotides and still code for the same amino acid,⁽³⁷⁶⁾ oligonucleotide primers could be constructed to replace nucleotides at one or more of these positions in each codon. A series of oligonucleotide primers could be used to replace these nucleotides and thus create a population of DNA molecules that vary in nucleotide sequence, but encode the same amino acid sequence.⁽³⁷⁷⁾

One problem occurs, however, at the five-prime end of the DNA constructs after the first round of mutagenesis because the primer used in the next round of mutagenesis must anneal to both the five-prime and three prime ends of the target sequence⁽³⁷⁸⁾ and a mixed population of DNA molecules will have been produced that vary in sequence at the five prime end. To solve this problem, each round of mutagenesis, after the first one, could use a mixed population of primers as shown in Figure 1(c) which contains primer molecules homologous to the five-prime end of each DNA molecule in the mutagenized population. Thus, by synthesizing a mixed population of primers, which vary at their five-prime ends, DNA molecules capable of hybridizing to both ends of the target sequence in the population can be produced. This technique could be used, for example, to generate all of the degenerate DNA sequences which encode a particular amino acid sequence. Further, once one DNA sequence, and thus the amino acid sequence of any encoded protein, is known, arguably, one skilled in molecular biology could use a codon usage chart⁽³⁷⁹⁾ to identify all of the DNA sequences capable of producing the subject protein and produce those DNA sequences. As a result, inclusion in the specification of techniques such as those shown in Figure 1 could be used to argue that the enablement requirement has been satisfied for generic claims that encompass all DNA sequences encoding one specific amino acid sequence.

Whether the written description requirement can be met by such a disclosure is a more difficult issue. In Amgen, the Federal Circuit noted that generic claims for DNA sequences could be valid when commensurate with the scope of the invention.⁽³⁸⁰⁾ However, in Fiers, the Federal Circuit noted that "[a]n adequate written description of a DNA requires . . . a description of the DNA itself."⁽³⁸¹⁾ The Federal Circuit further noted that Revel's description was inadequate because it did "not indicate that Revel was in possession of the DNA."⁽³⁸²⁾

If actual possession of each DNA molecule is necessary to satisfy the written description requirement, then presumably the only way to meet that requirement would be to actually synthesize each DNA molecule. It is not always necessary, however, for an applicant to make every embodiment of a claimed invention in order to obtain a patent.⁽³⁸³⁾ Thus, while "[a] bare reference to a DNA with a statement that it can be obtained"⁽³⁸⁴⁾ using a particular method is not an adequate written description,⁽³⁸⁵⁾ one could argue that each DNA molecule that encodes an amino acid is adequately described when one nucleotide sequence encoding that amino acid sequence is known and disclosed and methods for producing all of the other nucleotide sequences encoding the same amino acid sequence are provided.⁽³⁸⁶⁾ Further, at least for nucleic acid sequences encoding one specific amino acid sequence, all of the DNA sequences encompassed by such a generic claim can be described as shown in Figure 1(b).

5.  The Limits of Generic Claims

The allowance of generic claims for genetically engineered inventions by the PTO raises several issues. One such issue is the scope of generic claims which will be allowed by the PTO. Because the scope of generic claims must be tied to the scope of the disclosed invention,⁽³⁸⁷⁾ the PTO is unlikely to allow generic claims that encompass all DNA sequences encoding proteins with functional activities similar to those of a protein encoded by disclosed sequences. One argument for denying such claims is that they will often encompass prior art.⁽³⁸⁸⁾ Thus, regardless of satisfaction of the enablement requirement, the PTO is likely to allow generic claims for DNA sequences other than those that encode one amino acid sequence only when those claims encompass narrowly defined nucleic or amino acid sequences.⁽³⁸⁹⁾

A second issue is under what conditions generic claims will not be held invalid by the courts.⁽³⁹⁰⁾ The validity of generic claims for DNA sequences encoding proteins and functional analogs of those proteins will presumably be decided on a case-by-case basis with the courts focusing on whether the claims are commensurate with the scope of the invention and are adequately supported by the disclosure.⁽³⁹¹⁾ A practical reason for denying validity to claims of such broad scope is that, as the Amgen court pointed out with respect to claim seven, "the number of claimed DNA encoding sequences that can produce . . . [a protein with similar functional properties] is potentially enormous."⁽³⁹²⁾ As such, enforceable broad generic claims for nucleic sequences conflict with the policy objective of the issuance of patents for the promotion of the useful arts.⁽³⁹³⁾ Claims of such broad scope contravene this objective by leaving little for development by future inventors. Further, generic claims could also fail, as noted above,⁽³⁹⁴⁾ by encompassing subject matter in the prior art.⁽³⁹⁵⁾ Thus, as claims increase in scope, they encompass more subject matter and, hence, become increasingly subject to prior art limitations.

In summary, the limits of generic claims are presently unclear. This type of claim, however, has the potential for providing significant protection for genetically engineered inventions, but may only be useful in practice when the invention encompasses a variety of closely related molecules.

  Conclusion

The limitations placed on the doctrine of equivalents threaten to make the doctrine "a hollow and useless thing."⁽³⁹⁶⁾ The combination of the numerous limitations on the doctrine of equivalents and the rare situations in which literal infringement is found⁽³⁹⁷⁾ force applicants to make difficult choices in determining how to best protect their inventions.

With respect to applications claiming nucleic and amino acid sequences, when appropriate, generic claims may be useful for obtaining broad claim scope.

Further, the inclusion of site-directed and combinatorial mutagenic techniques in patent specifications, when the invention comprises a genetically engineered invention, could prove useful in a number of situations. For example, it could be argued during infringement litigation that the specification teaches one skilled in the art how to make and use DNA sequences that are the equivalent of natural allelic variations of the disclosed sequences. As yet, the Federal Circuit has not addressed the issue of whether claims to DNA sequences encompass natural allelic variants under the doctrine of equivalents.⁽³⁹⁸⁾ In addition, the inclusion of such techniques may be used to argue that the applicant has satisfied the enablement requirement for DNA sequence claims encompassing sequences related to those actually produced by the applicant and for claims encompassing all DNA sequences encoding one amino acid sequence.

Stephen G. Whiteside, Ph.D.^*

1. U.S. Const., art. 1, § 8, cl. 8. The United States Constitution confers upon Congress the power "[t]o promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries." Id.

2. Act of Apr. 10, 1790, ch. 7, § 2, 1 Stat. 109 (repealed 1793).

3. 35 U.S.C.A. § 154(a)(2) (Supp. 1996). "Every patent shall . . . grant to the patentee, his heirs or assigns, of the right to exclude others from making, using, offering for sale, or selling the invention throughout the United States or importing the invention into the United States . . . ." Id. § 154(a)(1).

4. 35 U.S.C. § 271 (1994).

5. Id.

6. Paul Overberg, USA More Inventive/Patent Fever Grips U.S. Inventors, USA Today, Oct. 21, 1994, at 1B. United States companies with extensive patent portfolios include AT&T, which was issued its 25,000th patent in 1994, and IBM, which is currently being issued patents at a rate of approximately 800 per year. Id.

7. Id.

8. Standard Oil Co. v. American Cyanamid Co., 774 F.2d 448, 452, 227 U.S.P.Q. (BNA) 293, 296 (Fed. Cir. 1985) ("[The prosecution history of a patent] includes all express representations made by or on behalf of the applicant . . . to induce a patent grant."). *Editor's Note: For the convenience of practitioners, parallel citations to the United States Patent Quarterly (U.S.P.Q. or U.S.P.Q.2d) have been included throughout this Note.

9. 35 U.S.C. § 131 (1994).

10. Id. § 101.

11. Id. ("Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new or useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.").

12. Id. This requisite usefulness is termed the "utility" requirement. Brenner v. Manson, 383 U.S. 519, 531 (1966). In 1966, the United States Supreme Court, while discussing the policy reasoning behind the utility requirement, stated the following:

The basic quid pro quo contemplated by the Constitution and the Congress for granting a patent monopoly is the benefit derived by the public from an invention with substantial utility. Unless and until a process is refined and developed to this point--where specific benefit exists in currently available form--there is insufficient justification for permitting an applicant to engross what may prove to be a broad field.Id. at 534-35.

13. 35 U.S.C. § 103 (1994).

14. See infra notes 32-41 and accompanying text.

15. 35 U.S.C. § 112 para. 1 (1994). Section 112 paragraph 1 provides the following:

The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains . . . to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.Id.

16. Id.

17. Id.

18. See generally Jeffrey G. Sheldon, How to Write a Patent Application §§ 7.2-.4 (1993).

19. 37 C.F.R. § 1.101 (1995); United States Dep't of Commerce, Patent & Trademark Office, Manual of Patent Examining Procedure §§ 702, 706 (6th ed. 1995) [hereinafter MPEP].

20. See generally 37 C.F.R. §§ 1.01-.133 (1995).

21. See generally Rochelle K. Seide & Melissa Szanto, Drafting Claims for Biotechnology Inventions, in G-401 Advanced Claim Drafting and Amendment Writing Workshop 1994, at 235 (1994).

22. MPEP, supra note 19, § 706.

23. 37 C.F.R. § 1.106 (1995); MPEP, supra note 19, § 706. See infra notes 42-55 and accompanying text for a description of patent claims.

24. 35 U.S.C. § 151 (1994); 37 C.F.R. § 1.311 (1995).

25. 37 C.F.R. § 1.113 (1995). Prosecution may continue after a final rejection; however, the examiner will generally only consider subject matter that either places the application in condition for allowance, or clarifies issues for appeal. Id. § 1.116.

26. 35 U.S.C. § 134 (1994); 37 C.F.R. §§ 1.113, .191 (1995).

27. 35 U.S.C. § 141 (1994) ("An applicant dissatisfied with the decision in an appeal to the Board of Patent Appeals and Interferences . . . may appeal the decision to the United States Court of Appeals for the Federal Circuit.").

28. Federal Courts Improvement Act of 1982, Pub. L. No. 97-164, 96 Stat. 25 (codified as amended in scattered sections of 5, 16, 18, 19, 25, 26, 28, 35, & 41 U.S.C.).

29. See Robert L. Harmon, Patents and the Federal Circuit ix (2d ed. 1994).

30. 37 C.F.R. § 1.81 (1995).

31. Id. § 1.51. The MPEP provides illustrative guidelines for the organization of patent applications and suggests division into the following sections:

(a) Title of the Invention.

(b) Cross-References to Related Applications (if any).

(c) Statement as to Rights to Inventions Made Under Federally Sponsored Research and Development (if any).

(d) Background of the Invention.

(1) Field of the Invention.

(2) Description of Related Art . . .

(e) Summary of the Invention.

(f) Brief Description of the Drawings.

(g) Description of the Preferred Embodiment(s).

(h) Claim(s).

(i) Abstract of the Disclosure (on a separate page).MPEP, supra note 19, § 601, at 600-2.

32. See Sheldon, supra note 18, § 7.5.

33. 35 U.S.C. § 112 (1994).

34. Id.

35. See Sheldon, supra note 18, § 7.5.

36. See id. § 7.5.8.3.

37. See id.

38. The Detailed Description is often referred to as the "Description," "Description of the Invention," "Description of the Preferred Embodiment(s)," or "Description of the Best Mode." Id. § 7.5.10.1.

39. Id. § 7.5.10.2; MPEP, supra note 19, § 601(g). See supra note 15 for the text of 35 U.S.C. § 112 para. 1 (1994).

40. See Sheldon, supra note 18, § 7.5.10.3.6.

41. See id. §§ 7.5.8.3, 7.5.10.3.6.

42. Id. § 6.1.1.

43. SmithKline Diagnostics, Inc. v. Helena Lab. Corp., 859 F.2d 878, 882, 8 U.S.P.Q.2d (BNA) 1468, 1471 (Fed. Cir. 1988) ("The claims of the [alleged infringed] patent measure the invention at issue . . . .").

The following are examples of claims from a recently issued patent:

What is claimed is:

1. A domestic composter structure for composting organic waste, having an upwardly tapered lower portion, an upwardly tapered upper portion sized, when reversed to fit within said lower portion to enable shipment of the composter within a passenger car when dis-assembled, said lower portion having an upper edge joint portion and said upper portion having a lower edge joint portion, said joint portions when solely manually assembled forming a locked joint composter construction.

2. The composter structure as set forth in claim 1, said joint portions being manually dis-assemblable without the use of tools.Raghunathan, U.S. Patent No. 5,339,974, col. 4, ll. 32-45.

44. 35 U.S.C. § 112 paras. 3, 6 (1994). Section 112 states in part:

A claim may be written in independent or, if the nature of the case admits, in dependent or multiple dependent form.

. . . .

An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof . . . .Id.; see also MPEP, supra note 19, § 608.01(m)-(n).

45. 35 U.S.C. § 112 para. 2 (1994) ("The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.").

46. See Sheldon, supra note 18, § 6.1.2.

47. 35 U.S.C. § 102(a) (1994). The statute reads as follows:

A person shall be entitled to a patent unless--

(a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for the patent, or

(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of the application for patent in the United States, or

. . . .

(g) before the applicant's invention thereof the invention was made in this country by another who had not abandoned, suppressed, or concealed it.Id. § 102(a)-(b), (g).

48. 37 C.F.R. § 1.104(a) (1995).

49. See Sheldon, supra note 18, § 6.1.2.

50. See id.

51. See generally MPEP, supra note 19, § 706.02.

52. See Sheldon, supra note 18, § 6.1.2.

53. 35 U.S.C. § 112 para. 1 (1994); 37 C.F.R. § 1.75(d)(1) (1995).

54. DMI, Inc. v. Deere & Co., 755 F.2d 1570, 1574 n.2, 225 U.S.P.Q. (BNA) 236, 238 n.2 (Fed. Cir. 1985) ("Claims are always interpretable in light of the specification and prosecution history of the application that led to the patent.").

55. SmithKline Diagnostics, Inc. v. Helena Lab. Corp., 859 F.2d 878, 882-83, 8 U.S.P.Q.2d (BNA) 1468, 1471 (Fed. Cir. 1988).

56. See generally Joseph Sambrook et al., Molecular Cloning: A Laboratory Manual (2d ed. 1989). The genetic materials of living organisms consist of nucleic acids. See generally Bruce Alberts et al., Molecular Biology of the Cell 104-07 (3d ed. 1994). Nucleic acids, which include both DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are chains of molecules called "nucleotides" attached to sugar-phosphate backbones. Id. at 98-99. DNA makes up the genetic code and is composed of four nucleotides: adenine (A); guanine (G); cytosine (C); and thymine (T). Id. The same nucleotides are also present in RNA, with the exception that thymine is substituted by a nucleotide called uracil (U). Id. at 104.

DNA normally is a double-stranded molecule; it is composed of two complementary strands that coil around each other in a double helix. Id. at 98-99. Specific nucleotides in one strand are always paired with specific nucleotides in the other strand. Id. For example, because A will pair only with T, and C will pair only with G, if A is the nucleotide in one strand, the corresponding nucleotide in the other strand must be T; if C is the nucleotide in one strand, the corresponding base in the complementary strand is G. Id. As a result of this complementary base pairing, by knowing the nucleotide sequence of one strand, the sequence of the other strand can be deduced. Id.

Cells use the properties of the nucleotides to pair only with their complementary nucleotide to copy their DNA. Id. at 251-52. During DNA replication, the two strands of DNA separate and new nucleotides are matched with the nucleotides in each strand, resulting in the formation of two identical double-stranded DNA molecules. Id.

A gene is a DNA sequence that generally encodes a particular product. Id. at G-10. In many instances, genes are composed of DNA sequences that encode proteins. Id. Proteins are essentially chains of amino acids. Id. at G-19. There are several steps that must be performed to produce a protein from a DNA sequence. Id. at 223-24. The first step, referred to as "transcription," is the creation of a messenger RNA (mRNA) copy of the DNA sequence encoding the protein intended for production. Id. at 223. To produce an mRNA molecule, the DNA strands separate and complementary nucleotides match with the nucleotides of one strand of the DNA. Id. at 224-26. For every A in the DNA sequence, a complementary nucleotide of U is incorporated into the RNA molecule; for every G on the DNA strand, a C is incorporated. Id. The production of mRNA is thus similar to DNA replication in that a complementary nucleic acid molecule is produced from a DNA strand. Id. at 98-99, 224-26.

After being transcribed, the mRNA molecule is then "translated" by "organelles" in the cell called "ribosomes." Id. at 231-34. A ribosome is effectively a miniature protein factory that "reads" the genetic code of the mRNA, and "constructs" a protein that meets the encoded specifications. Id. During translation, the nucleotides of the mRNA are read in groups of three that are referred to as "codons." Id. at 230. Each codon represents a specific amino acid in the encoded protein chain. Id. For example, the codon GGU generally encodes the amino acid glycine. Id. Because the A, C, G, and T nucleotides can combine to form 64 different triplet combinations, but only 20 different amino acids are commonly found in proteins, often more than one codon encodes the same amino acid. Id. For example, the codons GGU, GGG, GGA, and GGC all code for the amino acid glycine. Id. at 232. The genetic code is thus said to be degenerate, meaning that more than one codon can encode the same amino acid. Id. at 230-31. Due to this degeneracy, a considerable number of DNA sequences can encode the same protein. Id.

Proteins are initially produced as linear chains of amino acids. Id. at 111. These proteins generally become active upon folding into a particular three-dimensional conformation. Id. at 111-19, 128-30. In many instances, genes encode proteins that have one or more biological functions, such as the catalysis of a chemical reaction or the transcriptional regulation of a specific gene. Id. at 129-35, 417-32.

A variety of methods have been developed for isolating DNA sequences that encode useful products. See generally Sambrook et al., supra. After isolation, proteins can be produced from those DNA sequences. See generally id. Products derived from such biotechnology include proteins with pharmaceutically active properties and organisms, into which genes not native to those organisms have been inserted, with characteristics not found in nature. See Yamada et al., U.S. Patent No. 5,376,639 (claiming the treatment of sarcomas with interleukin-1 alpha); Rutherford et al., U.S. Patent No. 5,376,636 (claiming a method of promoting tissue regeneration and wound healing using platelet-derived growth factor and steroid hormones); Suslow et al., U.S. Patent No. 5,374,540 (claiming plant cells containing an expression vector encoding chitinase that is secreted from those cells).

57. See, e.g., In re Argoudelis, 434 F.2d 1390, 168 U.S.P.Q. (BNA) 99 (C.C.P.A. 1970) (addressing whether the enablement requirement for a subject matter comprising a microorganism is satisfied when the public is denied access to that microorganism until after issuance of the patent); Ex parte Allen, 2 U.S.P.Q.2d (BNA) 1425 (B.P.A.I. 1987) (addressing whether live, human-made polyploid oysters are patentable subject matter under 35 U.S.C. § 101); Ex parte Hibberd, 227 U.S.P.Q. (BNA) 443 (B.P.A.I. 1985) (addressing whether live, human-made plants are patentable subject matter under 35 U.S.C. § 101).

58. See, e.g., Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d (BNA) 1016 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).

59. See infra notes 60-75 and accompanying text.

60. Diamond v. Chakrabarty, 447 U.S. 303 (1980).

61. Id. at 308.

62. Id.

63. Id. at 307.

64. Id.

65. Diamond, 447 U.S. at 307.

66. 1077 Off. Gaz. Pat. Office 24 (Apr. 21, 1987).

67. Leder et al., U.S. Patent No. 4,736,866. A transgenic animal is an animal into which one or more genes not native to that animal have been inserted. Id. at col. 1, ll. 6-8. The invention described in U.S. Patent No. 4,736,866 comprised a strain of transgenic mice carrying an activatable transgene that induces the development of tumors with high frequency. Id. at col. 4, ll. 19-20. The mice carrying this transgene were intended for use as animal models for testing potential cancer-inducing agents. Id. at col. 8, ll. 53-54.

68. Animal Legal Defense Fund v. Quigg, 932 F.2d 920, 925, 18 U.S.P.Q.2d (BNA) 1677, 1682 (Fed. Cir. 1991).

69. Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1213, 18 U.S.P.Q.2d (BNA) 1016, 1027 (Fed. Cir.) (holding a generic claim for DNA sequences invalid for failure to meet the enablement requirement for all of the subject matter encompassed by that claim), cert. denied, 502 U.S. 856 (1991); In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d (BNA) 1400, 1406 (Fed. Cir. 1988) (noting that the enablement requirement mandates that a patent's disclosure must provide sufficient information to enable one skilled in the art to practice the invention without undue experimentation).

70. 35 U.S.C. § 112 para. 1 (1994).

71. In re Wands, 858 F.2d at 736, 8 U.S.P.Q.2d at 1403.

72. Id. at 737, 8 U.S.P.Q.2d at 1404; see also generally Karen S. Canady, The Wright Enabling Disclosure for Biotechnology Patents, 69 Wash. L. Rev. 455 (1994).

73. In re Wands, 858 F.2d at 737, 8 U.S.P.Q.2d at 1404 (citing In re Angstadt, 537 F.2d 498, 504, 190 U.S.P.Q. (BNA) 214, 219 (C.C.P.A. 1976)); see also id. ("`[A] considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed . . . .'" (omission in original) (quoting Ex parte Jackson, 217 U.S.P.Q. 804, 807 (B.P.A.I. 1982))).

74. Id. at 735, 8 U.S.P.Q.2d at 1403 (citing In re Lundak, 773 F.2d 1216, 1218, 227 U.S.P.Q. (BNA) 90, 92 (Fed. Cir. 1985); In re Argoudelis, 434 F.2d 1390, 1392-93, 168 U.S.P.Q. (BNA) 99, 101-02 (C.C.P.A. 1970)).

75. See generally MPEP, supra note 19, §§ 2402-2405.

76. See infra part II.

77. See infra part II.

78. See infra part II.A.3, B.4.

79. As used herein, an "accused device" refers to an item that allegedly infringes one or more of a patent's claims.

80. North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1574, 28 U.S.P.Q.2d (BNA) 1333, 1335 (Fed. Cir. 1993) (citing ZMI Corp. v. Cardiac Resuscitator Corp., 844 F.2d 1576, 1578, 6 U.S.P.Q.2d (BNA) 1557, 1559 (Fed. Cir. 1988)), cert. denied, 114 S. Ct. 1645 (1994).

81. Id.

82. Id.

83. Id. (citing Minnesota Mining & Mfg. Co. v. Johnson & Johnson Orthopaedics, Inc., 976 F.2d 1559, 1570, 24 U.S.P.Q.2d (BNA) 1321, 1330 (Fed. Cir. 1992)); see also Markman v. Westview Instruments, Inc., 52 F.3d 967, 979, 34 U.S.P.Q.2d (BNA) 1321, 1329 (Fed. Cir.) (en banc) ("[I]n a case tried to a jury, the court has the power and obligation to construe as a matter of law the meaning of language used in the patent claim. . . . Because claim construction is a matter of law, the construction given the claims is reviewed de novo on appeal."), cert. granted, 116 S. Ct. 40 (1995), and aff'd, 116 S. Ct. 1384 (1996).

84. Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605 (1950).

85. Id. at 607-08.

86. Id. at 608.

87. Id. (quoting Sanitary Refrigerator Co. v. Winters, 280 U.S. 30, 42 (1929)); cf. Hilton Davis Chem. Co. v. Warner-Jenkinson Co., 62 F.3d 1512, 1518, 35 U.S.P.Q.2d (BNA) 1641, 1645 (Fed. Cir. 1995) (en banc) ("[T]he application of the doctrine of equivalents rests on the substantiality of the differences between the claimed and accused products or processes, assessed according to an objective standard."), cert. granted, 116 S. Ct. 1014 (1996).

88. Laitram Corp. v. Rexnord, Inc., 939 F.2d 1533, 1535, 19 U.S.P.Q.2d 1367, 1369 (Fed. Cir. 1991) (citing Corning Glass Works v. Sumitomo Elec. U.S.A., Inc., 868 F.2d 1251, 1259, 9 U.S.P.Q.2d (BNA) 1962, 1967 (Fed. Cir. 1989)).

89. Graver Tank, 339 U.S. at 607.

90. Id.

91. See Hughes Aircraft Co. v. United States, 717 F.2d 1351, 1361, 219 U.S.P.Q. (BNA) 473, 480 (Fed. Cir. 1983).

92. Graver Tank, 339 U.S. at 607; see also Hughes Aircraft, 717 F.2d at 1363, 219 U.S.P.Q. at 481.

93. Texas Instruments v. United States Int'l Trade Comm'n, 805 F.2d 1558, 1572, 231 U.S.P.Q. (BNA) 833, 842 (Fed. Cir. 1986) ("[T]he incentive to innovation that flows from `inventing around' an adversely held patent must be preserved.").

94. Scripps Clinic & Research Found. v. Genentech, Inc., 927 F.2d 1565, 1581, 18 U.S.P.Q.2d (BNA) 1001, 1014 (Fed. Cir. 1991) ("[A]n accused article may avoid infringement, even if it is within the literal words of the claim, if it is `so far changed in principle from a patented article that it performs the same or a similar function in a substantially different way.'" (quoting Graver Tank, 339 U.S. at 608)).

95. Graver Tank, 339 U.S. at 608.

96. Id. at 608-09.

97. Markman v. Westview Instruments, Inc., 52 F.3d 967, 976, 34 U.S.P.Q.2d (BNA) 1321, 1326 (Fed. Cir.) (en banc) (citing Read Corp. v. Portec, Inc., 970 F.2d 816, 821, 23 U.S.P.Q.2d (BNA) 1426, 1431 (Fed. Cir. 1992)), cert. granted, 116 S. Ct. 40 (1995), and aff'd, 116 S. Ct. 1384 (1996).

98. Id. at 979, 34 U.S.P.Q.2d at 1329 ("`To ascertain the meaning of claims, we consider three sources: The claims, the specification, and the prosecution history.'" (quoting Unique Concepts, Inc. v. Brown, 939 F.2d 1558, 1561, 19 U.S.P.Q.2d (BNA) 1500, 1503 (Fed. Cir. 1991))).

99. SmithKline Diagnostics, Inc. v. Helena Lab. Corp., 859 F.2d 878, 882, 8 U.S.P.Q.2d (BNA) 1468, 1471 (Fed. Cir. 1988).

100. Wilson Sporting Goods Co. v. David Geoffrey & Assocs., 904 F.2d 677, 684, 14 U.S.P.Q.2d (BNA) 1942, 1948 (Fed. Cir.) ("To say that the doctrine of equivalents extends or enlarges the claims is a contradiction in terms. The claims--i.e., the scope of patent protection as defined by the claims--remain the same and application of the doctrine expands the right to exclude to `equivalents' of what is claimed."), cert. denied, 498 U.S. 992 (1990).

101. Coleco Indus., Inc. v. United States Int'l Trade Comm'n, 573 F.2d 1247, 1259, 197 U.S.P.Q. (BNA) 472, 481 (C.C.P.A. 1978) (Rich, J., concurring).

102. Perkin-Elmer Corp. v. Westinghouse Elec. Corp., 822 F.2d 1528, 1532, 3 U.S.P.Q.2d (BNA) 1321, 1324 (Fed. Cir. 1987).

103. Id.

104. Markman v. Westview Instruments, Inc., 52 F.3d 967, 978, 34 U.S.P.Q.2d (BNA) 1321, 1329 (Fed. Cir.) (en banc) ("[I]t is only fair (and statutorily required) that competitors be able to ascertain to a reasonable degree the scope of the patentee's right to exclude." (citing Merrill v. Yeomans, 94 U.S. 568, 573-74 (1877); Hogg v. Emerson, 47 U.S. (6 How.) 437, 484 (1848))), cert. granted, 116 S. Ct. 40 (1995), and aff'd, 116 S. Ct. 1384 (1996); see also Miles Lab., Inc. v. Shandon, Inc., 997 F.2d 870, 874, 27 U.S.P.Q.2d (BNA) 1123, 1126 (Fed. Cir. 1993).

105. Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 607 (1950). In Markman, the court stated the following with regard to the rights of a patent owner:

[C]ompetitors should be able to rest assured, if infringement litigation occurs, that a judge, trained in the law, will similarly analyze the text of the patent and its associated public record and apply the established rules of construction, and in that way arrive at the true and consistent scope of the patent owner's rights to be given legal effect.Markman, 52 F.3d at 979, 34 U.S.P.Q.2d at 1329.

106. Graver Tank, 339 U.S. at 607.

107. See generally Ronald E. Larson, Balancing the Competing Policies Underlying the Doctrine of Equivalents in Patent Law, 21 AIPLA Q.J. 1, 1-33 (1993).

108. Markman, 52 F.3d at 985, 34 U.S.P.Q.2d at 1335.

109. See infra part II.A.1.a-c. Limitations resulting from inequitable conduct are not discussed in this Note.

110. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1564, 31 U.S.P.Q.2d 1161, 1167 (Fed. Cir. 1994); North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1577, 28 U.S.P.Q.2d (BNA) 1333, 1337-38 (Fed. Cir. 1993), cert. denied, 114 S. Ct. 1645 (1994); Loctite Corp. v. Ultraseal Ltd., 781 F.2d 861, 871, 228 U.S.P.Q. (BNA) 90, 96 (Fed. Cir. 1985).

111. Wilson Sporting Goods Co. v. David Geoffrey & Assocs., 904 F.2d 677, 683, 14 U.S.P.Q.2d (BNA) 1942, 1948 (Fed. Cir.), cert. denied, 498 U.S. 992 (1990).

112. Exhibit Supply Co. v. Ace Patents Corp., 315 U.S. 126, 136 (1942) ("[I]t has long been settled that recourse may not be had to [the doctrine of equivalents] to recapture claims which the patentee has surrendered by amendment."); Loctite, 781 F.2d at 870, 228 U.S.P.Q. at 96.

113. Johnston v. IVAC Corp., 885 F.2d 1574, 1580, 12 U.S.P.Q.2d (BNA) 1382, 1386 (Fed. Cir. 1989) ("[C]laim interpretation may be resolved as an issue of law by the court on summary judgment taking into account the specification, prosecution history, or other evidence . . . ."); cf. Markman v. Westview Instruments, Inc., 52 F.3d 967, 979, 34 U.S.P.Q.2d (BNA) 1321, 1329 (Fed. Cir.) (en banc) (citing Unique Concepts, Inc. v. Brown, 939 F.2d 1558, 1559, 19 U.S.P.Q.2d (BNA) 1500, 1503 (Fed. Cir. 1991)), cert. granted, 116 S. Ct. 40 (1995), and aff'd, 116 S. Ct. 1384 (1996).

114. Johnston, 885 F.2d at 1579-80, 12 U.S.P.Q.2d at 1386. In Loctite, the court noted the following with regard to the doctrine of equivalents:

[W]henever the doctrine [of equivalents] is evoked, "a close examination must be made as to, not only what was surrendered, but also the reason for such a surrender;" [sic] the fact that claims were narrowed "does not always mean that the doctrine of file history estoppel completely prohibits a patentee from recapturing some of what was originally claimed."Loctite, 781 F.2d at 871, 228 U.S.P.Q. at 96 (quoting Bayer Aktiengesellschaft v. Duphar Int'l Research, B.V., 738 F.2d 1237, 1243, 222 U.S.P.Q. (BNA) 649, 653 (Fed. Cir. 1984)).

115. See Loctite, 781 F.2d at 871, 228 U.S.P.Q. at 96; Hughes Aircraft Co. v. United States, 717 F.2d 1351, 1363, 219 U.S.P.Q. (BNA) 473, 481 (Fed. Cir. 1983).

116. Hughes Aircraft, 717 F.2d at 1363, 219 U.S.P.Q. at 481 ("Amendment of claims is a common practice in prosecution of patent applications. . . . Amendments may be of different types and may serve different functions. Depending on the nature and purpose of an amendment, it may have a limiting effect within a spectrum ranging from great to small to zero.").

117. Id. at 1362-63, 219 U.S.P.Q. at 481.

118. Id. at 1363, 219 U.S.P.Q. at 481.

119. Hormone Research Found. v. Genentech, Inc., 904 F.2d 1558, 1564, 15 U.S.P.Q.2d (BNA) 1039, 1044 (Fed. Cir. 1990), cert. dismissed, 499 U.S. 955 (1991). The court indicated in Hormone Research Foundation that even statements made after the examiner had informed the applicant that the claims were allowable did "not automatically preclude application of prosecution history estoppel." Id. at 1565 n.9, 15 U.S.P.Q.2d at 1044 n.9.

120. Wilson Sporting Goods Co. v. David Geoffrey & Assocs., 904 F.2d 677, 684, 14 U.S.P.Q.2d (BNA) 1942, 1948 (Fed. Cir.) ("[A] patentee should not be able to obtain, under the doctrine of equivalents, coverage which he could not lawfully have obtained from the PTO by literal claims."), cert. denied, 498 U.S. 992 (1990).

121. See supra note 47 for the text of 35 U.S.C. § 102(a)-(b), (g) (1994).

122. Texas Instruments v. United States Int'l Trade Comm'n, 805 F.2d 1558, 1563, 231 U.S.P.Q. (BNA) 833, 835 (Fed. Cir. 1986) (citing Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U.S. 405, 414 (1908); Miller v. Eagle Mfg. Co., 151 U.S. 186, 207 (1894)).

123. Perkin-Elmer Corp. v. Westinghouse Elec. Corp., 822 F.2d 1528, 1532, 3 U.S.P.Q.2d (BNA) 1321, 1324 (Fed. Cir. 1987) (citing Sealed Air Corp. v. United States Int'l Trade Comm'n, 645 F.2d 976, 984, 209 U.S.P.Q. (BNA) 469, 477 (C.C.P.A. 1981)).

124. Wilson Sporting Goods Co. v. David Geoffrey & Assocs., 904 F.2d 677, 14 U.S.P.Q.2d (BNA) 1942 (Fed. Cir.), cert. denied, 498 U.S. 992 (1990).

125. Id. at 684, 14 U.S.P.Q.2d at 1948.

126. Id.

127. Id.

128. Id. at 685, 14 U.S.P.Q.2d at 1949.

129. Wilson Sporting Goods, 904 F.2d at 685-86, 14 U.S.P.Q.2d at 1949. Patents with multiple claims may contain one or more independent claims of broad scope and dependent claims that refer back to the independent claim or claims. See Sheldon, supra note 18, § 6.4. The dependent claims are generally more limited in scope than the independent claim. See supra note 43 for examples of independent and dependent claims.

130. Wilson Sporting Goods, 904 F.2d at 686, 14 U.S.P.Q.2d at 1949.

131. Id. at 685, 14 U.S.P.Q.2d at 1949.

132. Id. at 684, 14 U.S.P.Q.2d at 1948.

133. See generally Henrik D. Parker, Doctrine of Equivalents Analysis After Wilson Sporting Goods: The Hypothetical Claim Hydra, 18 AIPLA Q.J. 262 (1990) (reviewing a series of issues posed by the Wilson Sporting Goods decision).

134. International Visual Corp. v. Crown Metal Mfg., 991 F.2d 768, 26 U.S.P.Q.2d (BNA) 1588 (Fed. Cir. 1993).

135. Id. at 772, 26 U.S.P.Q.2d at 1591.

136. Id. (quoting Wilson Sporting Goods, 904 F.2d at 684, 14 U.S.P.Q.2d at 1948).

137. See id.

138. See supra notes 133-36 and accompanying text.

139. See Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1564, 31 U.S.P.Q.2d 1161, 1167 (Fed. Cir. 1994); North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1577, 28 U.S.P.Q.2d (BNA) 1333, 1337 (Fed. Cir. 1993), cert. denied, 114 S. Ct. 1645 (1994). In North American Vaccine, the court stated the following:

It is the responsibility of patent applicants to disclose their inventions adequately. There is no such disclosure of the concept of avoiding crosslinking along the backbone in this patent. Thus, an invention of that breadth does not meet the description requirement. . . . [T]he [patent's] examples are consistent with monofunctionality, not difunctionality. A patent applicant cannot disclose and claim an invention narrowly and then, in the course of an infringement suit, argue effectively that the claims should be construed to cover that which is neither described nor enabled in the patent.North Am. Vaccine, 7 F.3d at 1577, 28 U.S.P.Q.2d at 1337 (citations omitted).

140. North Am. Vaccine, 7 F.3d at 1577, 28 U.S.P.Q.2d at 1337. In North American Vaccine, the court did not dispute the contention of one of the inventors "that he intended to include difunctional molecules within the scope of the invention." Id.

141. Genentech, 29 F.3d at 1564, 31 U.S.P.Q.2d at 1167.

142. North Am. Vaccine, 7 F.3d at 1577, 28 U.S.P.Q.2d at 1337.

143. Genentech, 29 F.3d at 1564, 31 U.S.P.Q.2d at 1167.

144. North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 28 U.S.P.Q.2d (BNA) 1333 (Fed. Cir. 1993), cert. denied, 114 S. Ct. 1645 (1994).

145. Id. at 1573, 28 U.S.P.Q.2d at 1334. Claim 11, the only independent claim at issue, read: "`An antigenic-polysaccharide-protein conjugate wherein the polysaccharide and protein are covalently linked through a CH₂-NH-protein linkage to a terminal portion of the polysaccharide without significant crosslinking, said antigenic polysaccharide having a MW [molecular weight] above about 2,000.'" Id. (alteration in original) (quoting Jennings et al., U.S. Patent No. 4,356,170, claim 11). North American Vaccine was an exclusive licensee of U.S. Patent No. 4,356,170, which was owned by NRC. Id. at 1572, 28 U.S.P.Q.2d at 1334.

146. Jennings et al., U.S. Patent No. 4,356,170.

147. North Am. Vaccine, 7 F.3d at 1574, 28 U.S.P.Q.2d at 1334 (quoting Jennings et al., U.S. Patent No. 4,356,170, claim 11).

148. Id. at 1573, 28 U.S.P.Q.2d at 1334. The vaccines claimed by NRC's patent consisted of proteins conjugated to polysaccharides derived from microorganisms. Jennings et al., U.S. Patent No. 4,356,170. These proteins were linked to the polysaccharides to enhance the antigenic properties of the latter, and thus their effectiveness in vaccines. North Am. Vaccine, 7 F.3d at 1573, 28 U.S.P.Q.2d at 1334. Crosslinking between the polysaccharide molecules had previously been shown to result in decreased antigenicity, and was intended to be avoided by linking proteins to only one terminal portion of the polysaccharide molecules. Id.

149. North Am. Vaccine, 7 F.3d at 1573, 28 U.S.P.Q.2d at 1334.

150. Id. at 1575, 28 U.S.P.Q.2d at 1335. NRC did not contest the district court's determination that polysaccharide molecules with protein attached to a single terminal end did not infringe the claim at issue. Id. at 1574, 28 U.S.P.Q.2d at 1335. Further, while infringement under the doctrine of equivalents was initially pled, the complaint was amended and infringement under that doctrine was not argued before the district court. See Brief for Defendants-Appellees at 4, North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 28 U.S.P.Q.2d (BNA) 1333 (Fed. Cir. 1993) (No. 93-1076).

151. North Am. Vaccine, 7 F.3d at 1575-76, 28 U.S.P.Q.2d at 1336 (quoting Jennings et al., U.S. Patent No. 4,356,170).

152. Id. (citing Robert C. Faber, Landis on Mechanics of Patent Claim Drafting 531 (3d ed. 1990)).

153. Id. at 1576, 28 U.S.P.Q.2d at 1336.

154. Id.

155. Id.

156. North Am. Vaccine, 7 F.3d at 1576-77, 28 U.S.P.Q.2d at 1337.

157. Id. at 1577, 28 U.S.P.Q.2d at 1337.

158. Id. at 1576, 28 U.S.P.Q.2d at 1337.

159. Id. at 1577, 28 U.S.P.Q.2d at 1337 (citing Carmen Indus., Inc. v. Wahl, 724 F.2d 932, 937 n.5, 220 U.S.P.Q. (BNA) 481, 485 n.5 (Fed. Cir. 1983)).

160. Id.

161. North Am. Vaccine, 7 F.3d at 1579, 28 U.S.P.Q.2d at 1339.

162. Id. at 1574-75, 28 U.S.P.Q.2d at 1335. As Judge Rader noted in a dissenting opinion, the American Cyanamid vaccine comprised a mixture of polysaccharide molecules, 50% of which had proteins attached to only one end. Id. at 1583, 28 U.S.P.Q.2d at 1342 (Rader, J., dissenting). Accordingly, Judge Rader believed that the accused vaccine literally infringed an open-ended claim of the patent at issue. Id. (Rader, J., dissenting). The issue of whether North American Vaccine's patent had been infringed by vaccines containing polysaccharide molecules with protein attached at a single terminal, however, was not before the court. Id. at 1574-75, 28 U.S.P.Q.2d at 1335.

163. Id. at 1577, 28 U.S.P.Q.2d at 1337-38.

164. Id. at 1574, 28 U.S.P.Q.2d at 1334-35.

165. Id. at 1577, 28 U.S.P.Q.2d at 1337.

166. North Am. Vaccine, 7 F.3d. at 1577-78, 28 U.S.P.Q.2d at 1337-38.

167. Id. at 1576, 28 U.S.P.Q.2d at 1336.

168. Id. at 1577, 28 U.S.P.Q.2d at 1337.

169. See id.

170. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 31 U.S.P.Q.2d (BNA) 1161 (Fed. Cir. 1994).

171. Id. at 1563, 31 U.S.P.Q.2d at 1166-67. The specifications of two patents at issue were virtually identical because these patents resulted from divisional applications derived from a common parent. Id. at 1563 n.14, 31 U.S.P.Q.2d at 1167 n.14. For simplicity, the court referred to the specification of only one of these patents. Id.

172. Id. at 1563-64, 31 U.S.P.Q.2d at 1166-67. The Genentech court noted the following four definitions of t-PA:

First, there is a narrow structural definition: t-PA produced through recombinant DNA technology but having the same structure as natural t-PA. Second, there is a broader structural definition: all products containing the "essential" Kringle region, and the Serine Protease region. Third, there is an even broader structural definition: all products containing just the enzymatically active portion, i.e., the Serine Protease portion. Fourth, there is a functional definition: "[I]t is capable of catalyzing the conversion of plasminogen to plasmin, binds to fibrin, and is classified as a t-PA based on immunological properties as set forth hereinabove."Id., 31 U.S.P.Q.2d at 1167 (alteration in original) (footnotes omitted) (quoting Goeddel et al., U.S. Patent No. 4,766,075, col. 6, ll. 15-19). t-PA is a protein that aids in dissolving blood clots. Id. at 1557, 31 U.S.P.Q.2d at 1162.

173. Id. at 1564, 31 U.S.P.Q.2d at 1167.

174. Id.

175. Genentech, 29 F.3d at 1564, 31 U.S.P.Q.2d at 1167.

176. Id. According to the court:

An applicant should not be able deliberately to narrow the scope of examination to avoid during prosecution scrutiny by the PTO of subject matter with the objective of more quickly obtaining a patent (or avoiding the risk of an estoppel), and then obtain in court, either literally or under the doctrine of equivalents, a scope of protection which encompasses that subject matter.Id. (citing North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1577, 28 U.S.P.Q.2d (BNA) 1333, 1337 (Fed. Cir. 1993), cert. denied, 114 S. Ct. 1645 (1994)).

177. Id. at 1564-65, 31 U.S.P.Q.2d at 1168 (citing Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1214, 18 U.S.P.Q.2d (BNA) 1016, 1029 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991); In re Fisher, 427 F.2d 833, 838-40, 166 U.S.P.Q. (BNA) 18, 23-24 (C.C.P.A. 1970)).

178. Id. at 1565, 31 U.S.P.Q.2d at 1168.

179. Goeddel et al., U.S. Patent No. 4,766,075, col. 5, l. 4 to col. 6, l. 19.

180. See id.

181. Genentech, 29 F.3d at 1564-65, 31 U.S.P.Q.2d at 1168.

182. See Goeddel et al., U.S. Patent No. 4,766,075, col. 5, l. 4 to col. 6, l. 19.

183. See id.

184. Genentech, 29 F.3d at 1567, 31 U.S.P.Q.2d at 1168.

185. Id. at 1568-69, 31 U.S.P.Q.2d at 1170-71 (comparing the allegedly infringing protein, FE1X, and natural t-PA from both structural and functional perspectives when determining the issue of infringement under the doctrine of equivalents, and ultimately holding that FE1X did not infringe patents claiming natural t-PA because FE1X has structural and functional properties distinguishable from those disclosed for natural t-PA).

186. Id. at 1567, 31 U.S.P.Q.2d at 1170 (citing Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 609 (1950); Zenith Lab., Inc. v. Bristol-Meyers Squibb Co., 19 F.3d 1418, 1425, 30 U.S.P.Q.2d (BNA) 1285, 1291 (Fed. Cir. 1994)).

187. See infra notes 205-29 for a discussion of the effect that these limitations had on the outcome of the litigation.

188. See supra notes 139-87 and accompanying text.

189. North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1577, 28 U.S.P.Q.2d (BNA) 1333, 1338 (Fed Cir. 1993), cert. denied, 114 S. Ct. 1645 (1994).

190. Genentech, 29 F.3d at 1564, 31 U.S.P.Q.2d at 1167.

191. North Am. Vaccine, 7 F.3d at 1577, 28 U.S.P.Q.2d at 1338.

192. See Genentech, 29 F.3d at 1564, 31 U.S.P.Q.2d at 1167.

193. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 31 U.S.P.Q.2d (BNA) 1161 (Fed. Cir. 1994).

194. As used in this Note, the phrase "genetically engineered invention" refers to products produced by the employment of genetic engineering techniques. One example of such an invention would be a DNA sequence and an amino acid sequence, if any, which that DNA sequence encodes.

195. See infra notes 254-62 and accompanying text.

196. Collen et al., U.S. Patent No. 4,752,603 (claiming t-PA extracted from human cancer cells).

197. Goeddel et al., U.S. Patent No. 4,766,075 (claiming a DNA sequence encoding human t-PA protein, a vector capable of expressing the protein, as well as mammalian cells containing the claimed expression vector).

198. Goeddel et al., U.S. Patent No. 4,853,330 (claiming the process of producing human t-PA using the expression vector and a cell line containing that vector).

199. Genentech, 29 F.3d at 1557, 31 U.S.P.Q.2d at 1161.

200. See supra notes 196-98.

201. Genentech, 29 F.3d at 1557, 31 U.S.P.Q.2d at 1161.

202. The amino acid sequence of met-t-PA is identical to that of natural t-PA with the exception that a single amino acid has been replaced in met-t-PA. Id. at 1559 n.4, 29 U.S.P.Q.2d at 1163 n.4. FE1X is a modified recombinant form of natural t-PA wherein the Finger (F) and Epidermal Growth Factor (E) regions have been deleted and an amino acid substitution has occurred at position 117, resulting in the loss of a glycosylation site. Id. As a result, FE1X has 15% fewer amino acids and has a half-life in circulation approximately 10 times longer than natural t-PA. Id.

203. Genentech, Inc. v. Wellcome Found. Ltd., 798 F. Supp. 213, 214, 24 U.S.P.Q.2d 1782, 1783 (D. Del. 1992), rev'd, 29 F.3d 1555, 31 U.S.P.Q.2d (BNA) 1161 (Fed. Cir. 1994).

204. Id.

205. Genentech, 29 F.3d at 1565, 31 U.S.P.Q.2d at 1169 (footnote omitted). Of the patents at issue, only U.S. Patent No. 4,752,603 (`603 patent) contained claims with explicit specific activity limitations. Id. at 1558-59, 31 U.S.P.Q.2d at 1162-63. Specific activity can be used as a measurement of the purity of an enzyme, and this activity is generally denoted in terms of units per milligram of protein. See Rodney F. Boyer, Modern Experimental Biochemistry 305-06 (2d ed. 1993). In the `603 patent, the specific activity was designated in International Units per milligram of material (IU/mg). Genentech, 29 F.3d at 1558, 31 U.S.P.Q.2d at 1162.

206. Genentech, 29 F.3d at 1562, 31 U.S.P.Q.2d at 1166.

207. Id. at 1566, 31 U.S.P.Q.2d at 1170.

208. Id. at 1567, 31 U.S.P.Q.2d at 1170.

209. Id.

210. See supra notes 170-78 and accompanying text.

211. Genentech, 29 F.3d at 1563, 31 U.S.P.Q.2d at 1166-67.

212. Markman v. Westview Instruments Inc., 52 F.3d 967, 980, 34 U.S.P.Q.2d (BNA) 1321, 1330 (Fed. Cir.) (en banc), cert. granted, 116 S. Ct. 40 (1995), and aff'd, 116 S. Ct. 1384 (1996); Hormone Research Found., Inc. v. Genentech, Inc., 904 F.2d 1558, 1563, 15 U.S.P.Q.2d (BNA) 1039, 1043 (Fed. Cir. 1990) (citing Fromson v. Advance Offset Plate, Inc., 720 F.2d 1565, 1569, 219 U.S.P.Q. (BNA) 1137, 1140 (Fed. Cir. 1983)).

213. Genentech, 29 F.3d at 1563-64, 31 U.S.P.Q.2d at 1167.

214. Id. at 1564, 31 U.S.P.Q.2d at 1168; see also supra notes 174-78 and accompanying text.

215. Genentech, 29 F.3d at 1563, 31 U.S.P.Q.2d at 1168 (footnote omitted).

216. Id. at 1565 n.27, 31 U.S.P.Q.2d at 1168 n.27 (failing to reach the issue of whether natural t-PA encompasses naturally occurring variants of human t-PA). In many instances, allelic variants of proteins are present in different individuals. These allelic variants vary in amino acid sequence as compared to the subject protein. See id. at 1563 n.16, 31 U.S.P.Q.2d at 1167 n.16 (quoting Goeddel et al., U.S. Patent No. 4,766,075); see also generally Alberts et al., supra note 56, at 1013, 1072.

217. Genentech, 29 F.3d at 1567, 31 U.S.P.Q.2d at 1170 (footnote omitted).

218. Id.

219. See supra notes 84-88 and accompanying text.

220. Genentech, 29 F.3d at 1567, 31 U.S.P.Q.2d at 1170.

221. Id. at 1567-69, 31 U.S.P.Q.2d at 1170-71. The Genentech court stated the following:

If, as the trial court thought, a broad definition [of t-PA] is appropriate--stimulating "the dissolution of fibrin clots through the cleavage of plasminogen to plasmin"--then it is difficult to imagine how FE1X, or any version of t-PA for that matter, would avoid infringement under the doctrine of equivalents because t-PA, or any operative variant, would by definition necessarily perform this function in the same general way with the same general results. However, if the definition of t-PA set forth in the specification is adopted--catalyzing the conversion of plasminogen to plasmin, [and] bind[ing] to fibrin--then the equivalence question becomes a much closer one.Id. at 1567, 31 U.S.P.Q.2d at 1170-71 (second and third alterations in original) (citations omitted) (footnotes omitted). The Genentech court also made the following observation:

The operative definition for purposes of equivalency analysis is the intended function as seen in the context of the patent, the prosecution history, and the prior art. . . . As noted, the specification expressly defines fibrin binding as a critical component of the "function" of human t-PA. . . . [A] functional definition of t-PA which ignores this distinction would result in a range of equivalents which impermissibly reads on the prior art.Id. at 1567-68, 31 U.S.P.Q.2d at 1170-71 (citations omitted) (footnote omitted).

222. Id. at 1567, 31 U.S.P.Q.2d at 1171.

223. Id. at 1567-68, 31 U.S.P.Q.2d at 1170-71.

224. See id. at 1568, 31 U.S.P.Q.2d at 1171.

225. A domain is a region of a protein that has a defined three-dimensional structure that is formed when the amino acid chain folds back on itself. See Alberts et al., supra note 56, at 116-23. These domains often confer one or more functional activities on the protein. See id. For example, zinc finger domains have been shown to confer DNA binding properties. Id. at 410-11. Natural t-PA consists of five domains, each believed to have separate biological functions. Genentech, 29 F.3d at 1559 n.4, 31 U.S.P.Q.2d at 1163 n.4.

226. Genentech, 29 F.3d at 1568-69, 31 U.S.P.Q.2d at 1171.

227. Genentech, 29 F.3d at 1569 n.42, 31 U.S.P.Q.2d at 1171 n.42 ("The `half-life' is a measurement of the length of time a dosage is retained in the human body.").

228. Id. at 1569, 31 U.S.P.Q.2d at 1171 (footnote omitted).

229. Id., 31 U.S.P.Q.2d at 1171-72.

230. See infra notes 231-41 and accompanying text.

231. Genentech, 29 F.3d at 1568-69, 31 U.S.P.Q.2d at 1171.

232. Id., 31 U.S.P.Q.2d at 1171-72.

233. See, e.g., Yagasaki et al., U.S. Patent No. 5,376,545 (claiming a DNA molecule encoding a protein with uricase activity having the amino acid sequence disclosed in the patent specification and a method of producing that protein); Gelfand et al., U.S. Patent No. 5,374,553 (claiming a nucleic acid encoding a thermostable DNA polymerase protein); Murphy et al., U.S. Patent No. 5,374,506 (claiming an isolated interleukin-8 receptor protein).

234. See generally Alberts et al., supra note 56, at 116-23.

235. See generally id.

236. See, e.g., Williams, U.S. Patent No. 5,376,367 (claiming a fusion protein comprising mast cell growth factor and interleukin-3); Boquet et al., U.S. Patent No. 5,362,644 (claiming DNA encoding a multiple component hybrid protein); Stengelin et al., U.S. Patent No. 5,358,857 (claiming a method for producing fusion proteins); Pastan et al., U.S. Patent No. 5,328,984 (claiming recombinant chimeric proteins comprising a protein for which delivery into a cell is desired, Domain II of Pseudomonas exotoxin, which allows for translocation across cell membranes, and a segment of a third protein, which promotes binding of the chimeric protein to the cell type of interest).

237. See supra notes 217-29 and accompanying text.

238. See supra notes 217-29 and accompanying text.

239. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1568-69, 31 U.S.P.Q.2d (BNA) 1161, 1171-72 (Fed. Cir. 1994) (holding no infringement under the doctrine of equivalents of patents claiming a DNA sequence encoding a protein by a modified form of the encoded protein in which two of five functional domains were deleted and the final product possessed altered functional properties).

240. Cf. id. at 1567, 31 U.S.P.Q.2d at 1171 (noting that the intended function of claimed subject matter, as determined by "the context of the patent, the prosecution history, and the prior art," is used to formulate an operative definition of that subject matter for equivalency analysis).

241. See supra notes 217-29 and accompanying text.

242. See cases cited infra note 245.

243. See supra notes 14-18 and accompanying text.

244. U.S. Const., art. 1, § 8, cl. 8.

245. United States Steel Corp. v. Phillips Petroleum Co., 865 F.2d 1247, 1251-52, 9 U.S.P.Q.2d (BNA) 1461, 1465 (Fed. Cir. 1989) (noting that to refuse to allow a patent disclosure, which is enabling as of the filing date, to cover later developed forms of the invention would place an impossible burden on inventors). But cf. Texas Instruments v. United States Int'l Trade Comm'n, 805 F.2d 1558, 1572, 231 U.S.P.Q. (BNA) 833, 841 (Fed. Cir. 1986) ("[T]he extensive technological advances in all of the claimed functions support the . . . finding that the accused devices are not equivalent to the claimed invention . . . .").

246. In re Wright, 999 F.2d 1557, 1561, 27 U.S.P.Q.2d (BNA) 1510, 1513 (Fed. Cir. 1993) (citing In re Vaeck, 947 F.2d 488, 495, 20 U.S.P.Q.2d (BNA) 1438, 1444 (Fed. Cir. 1991); In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q.2d (BNA) 1400, 1404 (Fed. Cir. 1988); In re Fisher, 427 F.2d 833, 839, 166 U.S.P.Q. (BNA) 18, 24 (C.C.P.A. 1970)).

247. Texas Instruments, 805 F.2d at 1563, 231 U.S.P.Q. at 835 ("This court has cautioned against limiting the claimed invention to preferred embodiments or specific examples in the specification." (citing Palumbo v. Don-Joy Co., 762 F.2d 969, 977, 226 U.S.P.Q. (BNA) 5, 10 (Fed. Cir. 1985))); see also Loctite Corp. v. Ultraseal Ltd., 781 F.2d 861, 867, 228 U.S.P.Q. (BNA) 90, 95 (Fed. Cir. 1985) (noting that when determining infringement under the doctrine of equivalents, the accused device is compared to the invention as claimed, not the embodiments).

248. See supra notes 104-09 and accompanying text.

249. See supra notes 93-96 and accompanying text.

250. See Alberts et al., supra note 56, at 120-23.

251. This conclusion is based on the fact that there are a finite number of functional domains and many proteins differ in structure and function based on which domains they contain. See generally Alberts et al., supra note 56, at 116-23.

252. See supra notes 101-03 and accompanying text.

253. Cf. Hilton Davis Chem. Co. v. Warner-Jenkinson Co., 62 F.3d 1512, 1518, 35 U.S.P.Q.2d (BNA) 1641, 1645 (Fed. Cir. 1995) (en banc) ("[T]he application of the doctrine of equivalents rests on the substantiality of the differences between the claimed and accused products or processes, assessed according to an objective standard."), cert. granted, 116 S. Ct. 1014 (1996).

254. Genentech, Inc. v. Wellcome Found. Ltd., 798 F. Supp. 213, 216, 24 U.S.P.Q.2d 1782, 1785 (D. Del. 1992), rev'd, 29 F.3d 1555, 31 U.S.P.Q.2d (BNA) 1161 (Fed. Cir. 1994).

255. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1560, 31 U.S.P.Q.2d (BNA) 1161, 1164 (Fed. Cir. 1994)

256. Id. at 1559 n.4, 31 U.S.P.Q.2d at 1163 n.4.

257. Id. at 1560, 31 U.S.P.Q.2d at 1164.

258. See infra notes 259-62 and accompanying text.

259. This assumption is derived from the fact that the Wellcome Foundation focused the bulk of its arguments during the district court proceeding, on the invalidity of the patents at issue. Genentech, 798 F. Supp. at 216-18, 24 U.S.P.Q.2d at 1785-86. This suggests that met-t-PA has functional properties quite similar to those of natural t-PA.

260. Genentech, 29 F.3d at 1559 n.4, 31 U.S.P.Q.2d at 1163 n.4.

261. See id. at 1567, 31 U.S.P.Q.2d at 1170.

262. Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608 (1950) (quoting Sanitary Refrigerator Co. v. Winters, 280 U.S. 30, 42 (1929)).

263. Genentech, 29 F.3d at 1567, 31 U.S.P.Q.2d at 1170; cf. Hormone Research Found. v. Genentech, Inc., 904 F.2d 1558, 1563-64, 15 U.S.P.Q.2d (BNA) 1039, 1044 (Fed. Cir. 1990), cert. dismissed, 499 U.S. 955 (1991).

264. This conclusion is based on the facts that claims may be infringed literally or under the doctrine of equivalents, see supra notes 84-86 and accompanying text, and minor modification of genetically engineered inventions will result in products that do not literally infringe claims for such an invention. See supra note 263 and accompanying text.

265. See supra notes 84-86, 263 and accompanying text.

266. Graver Tank, 339 U.S. at 607.

267. See supra part II.A.1 for a discussion of limitations on claim construction.

268. See infra notes 269-86 and accompanying text.

269. See infra part II.B for a discussion of generic claims.

270. While the standards for allowability of claims by the PTO and their validity during litigation are generally the same, there are instances when claims allowed by the PTO are held invalid by the courts. See, e.g., Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1214, 18 U.S.P.Q.2d (BNA) 1016, 1029 (Fed. Cir.) (holding a generic claim for DNA sequences invalid for lack of enablement), cert. denied, 502 U.S. 856 (1991)).

271. See supra part II.A.1.

272. See id.

273. Whether such claims are valid is currently an open question. See infra notes 340-57 and accompanying text for a discussion of this topic.

274. See North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1577, 28 U.S.P.Q.2d (BNA) 1333, 1337-38 (Fed. Cir. 1993), cert. denied, 114 S. Ct. 1645 (1994).

275. See supra part II.A.1 for a discussion of limitations on claim construction.

276. See supra notes 117-19 and accompanying text.

277. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1564, 31 U.S.P.Q.2d (BNA) 1161, 1167 (Fed Cir. 1994).

278. North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1577, 28 U.S.P.Q.2d (BNA) 1333, 1337 (Fed Cir. 1993), cert. denied, 114 S. Ct. 1645 (1994).

279. Id. at 1577, 28 U.S.P.Q.2d at 1337.

280. Genentech, 29 F.3d at 1564, 31 U.S.P.Q.2d at 1167.

281. See supra notes 217-29 and accompanying text. Claiming proteins as a single invention is roughly analogous to claiming an automobile as a single invention. Such claims, according to the reasoning of Genentech, see Genentech, 29 F.3d at 1568-69, 31 U.S.P.Q.2d at 1171, would not prevent others from making, using or selling the windshield or transmission of the claimed invention. See id.

282. See, e.g., Alberts et al., supra note 56, at 122-23 (describing how the functions of newly identified proteins are often determined by comparing their amino acid sequences with those of proteins with known functions). But cf. Benigno C. Valdez et al., Identification of the Nuclear and Nucleolar Localization Signals of the Protein p120, 269 J. Biological Chemistry 23776 (1994) (identifying by functional analysis amino acid sequences conferring localization of proteins to the nucleus and nucleolus).

283. See supra part II.A.1.b for a discussion of prior art limitations on patentability.

284. See, e.g., Alberts et al., supra note 56, at 122-23.

285. See, e.g., id. (describing some methods used to identify the function of protein domains).

286. See generally John E. Vicks, Jr., Publish and Perish: The Patented Publication as a Bar to Patentability, 18 AIPLA Q.J. 235 (1990).

287. The MPEP provides a general definition of a generic claim as a claim that encompasses a number of illustrated species or defines "an element or subcombination common to the several species." MPEP, supra note 19, § 806.04(d). Further, "a claim may include two or more of the disclosed embodiments within the breadth of the invention." Id. § 806.04(e).

288. See, e.g., In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d (BNA) 1210 (Fed. Cir. 1995); Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d (BNA) 1016 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991); Fiddes v. Baird, 30 U.S.P.Q.2d (BNA) 1481 (B.P.A.I. 1994); cf. In re Wands, 858 F.2d 731, 8 U.S.P.Q.2d (BNA) 1400 (Fed. Cir. 1988); Ex parte Anderson, 30 U.S.P.Q.2d (BNA) 1866 (B.P.A.I. 1994).

289. North Am. Vaccine, Inc. v. American Cyanamid Co., 7 F.3d 1571, 1574, 28 U.S.P.Q.2d (BNA) 1333, 1335 (Fed Cir. 1993) (citing Hi-Life Prod., Inc. v. American Nat'l Water-Mattress Corp., 842 F.2d 323, 325, 6 U.S.P.Q.2d (BNA) 1132, 1133 (Fed. Cir. 1988)), cert. denied, 114 S. Ct. 1645 (1994).

290. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1567, 31 U.S.P.Q.2d (BNA) 1161, 1170 (noting that a modified recombinant form of a protein, FE1X, did not literally infringe patents encompassing the natural protein, natural t-PA, because FE1X "is not natural t-PA"); cf. Hormone Research Found. v. Genentech, Inc., 904 F.2d 1558, 1563-64, 15 U.S.P.Q.2d (BNA) 1039, 1044 (Fed. Cir. 1990). In Genentech, the court determined the issue of whether claims for a DNA sequence encoding natural t-PA and the process of producing that protein were infringed by comparing the accused protein to the protein encoded by the claimed DNA sequences. Genentech, 29 F.3d at 1558-59, 1567-69, 31 U.S.P.Q.2d at 1162-63, 1170-72.

291. See supra note 56.

292. See In re Bell, 991 F.2d 781, 784, 26 U.S.P.Q.2d (BNA) 1529, 1531 (Fed. Cir. 1993) (noting that, due to the degeneracy of the genetic code, 10³⁶ nucleotide sequences could encode the amino acid sequence of the protein at issue). One issue left unaddressed by the Genentech court was whether claims for "`human tissue plasminogen activator' . . . include[] within [their] scope naturally-occurring variants of the full-length sequence." Genentech, 29 F.3d at 1565 n.27, 31 U.S.P.Q.2d at 1169 n.27.

293. See generally Alberts et al., supra note 56, at 120-21. In many instances, specific amino acids can be added, removed or replaced without affecting the functional characteristics of a protein. Id.

294. See Genentech, 29 F.3d at 1567, 31 U.S.P.Q.2d at 1170.

295. 35 U.S.C. § 112 para. 2 (1994).

296. SmithKline Diagnostics, Inc. v. Helena Labs Corp., 859 F.2d 878, 882, 8 U.S.P.Q.2d (BNA) 1468, 1471 (Fed. Cir. 1988).

297. Miles Lab., Inc. v. Shandon Inc., 997 F.2d 870, 874, 27 U.S.P.Q.2d (BNA) 1123, 1126 (Fed. Cir. 1993) (citing Orthokinetics, Inc. v. Safety Travel Chairs Inc., 806 F.2d 1565, 1576, 1 U.S.P.Q.2d (BNA) 1081, 1088 (Fed. Cir. 1986)), cert. denied, 114 S. Ct. 943 (1994).

298. Utter v. Hiraga, 845 F.2d 993, 998, 6 U.S.P.Q.2d (BNA) 1709, 1714 (Fed. Cir. 1988) (citing Ralston Purina Co. v. Far-Mar-Co, Inc., 772 F.2d 1570, 1575, 227 U.S.P.Q. (BNA) 177, 179 (Fed. Cir. 1985)).

299. In re Wands, 858 F.2d 731, 735, 8 U.S.P.Q.2d (BNA) 1400, 1402 (Fed Cir. 1988) (citing 35 U.S.C. § 112 para. 1).

300. Utter, 845 F.2d at 998, 6 U.S.P.Q.2d at 1714 (citing Atlas Powder Co. v. E.I. DuPont De Nemours & Co., 750 F.2d 1569, 1576, 224 U.S.P.Q. (BNA) 409, 413 (Fed. Cir. 1984)); see also In re Wands, 858 F.2d at 736-37, 8 U.S.P.Q.2d at 1404.

301. In re Wands, 858 F.2d at 736-37, 8 U.S.P.Q.2d at 1404-05 (citations omitted).

302. Utter, 845 F.2d at 998, 6 U.S.P.Q.2d at 1714 (citing Ralston Purina, 772 F.2d at 1575, 227 U.S.P.Q. at 179); cf. In re Wands, 858 F.2d at 736, 8 U.S.P.Q.2d at 1402-03 (citations omitted).

303. In re Wands, 858 F.2d at 737, 8 U.S.P.Q.2d at 1404. The Federal Circuit in In re Wands stated that eight factors are to be considered when determining whether the disclosure is non-enabling by requiring undue experimentation. These factors had been discussed in Ex parte Forman, 230 U.S.P.Q. (BNA) 546, 547 (B.P.A.I. 1986) as follows:

[T]he quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims.Id. (footnotes omitted).

304. In re Fisher, 427 F.2d 833, 839, 166 U.S.P.Q. (BNA) 18, 24 (C.C.P.A. 1970). The In re Fisher Court of Customs and Patent Appeals stated the following:

[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art. In cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.Id.

305. In re Vaeck, 947 F.2d 488, 496, 20 U.S.P.Q.2d (BNA) 1438, 1445 (Fed. Cir. 1991) (citing In re Angstadt, 537 F.2d 498, 502-03, 190 U.S.P.Q. (BNA) 214, 218 (C.C.P.A. 1976)).

306. Id.

307. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1561, 19 U.S.P.Q.2d (BNA) 1111, 1115 (Fed. Cir. 1991) ("`[I]t is possible for a specification to enable the practice of an invention as broadly as it is claimed, and still not describe that invention.'" (quoting In re DiLeone, 436 F.2d 1404, 1405, 168 U.S.P.Q. (BNA) 592, 593 (C.C.P.A. 1971))).

308. See 35 U.S.C. § 112 para. 1 (1994).

309. Utter v. Hiraga, 845 F.2d 993, 998, 6 U.S.P.Q.2d 1709, 1714 (Fed. Cir. 1988) ("A specification may, within the meaning of 35 U.S.C. § 112 ¶ 1, contain a written description of a broadly claimed invention without describing all species that claim encompasses." (citing Ralston Purina Co. v. Far-Mar-Co, Inc., 772 F.2d 1570, 1575, 227 U.S.P.Q. 177, 179 (Fed. Cir. 1985); In re Rasmussen, 650 F.2d 1212, 1215, 211 U.S.P.Q. (BNA) 323, 326 (C.C.P.A. 1981))).

310. Fiers v. Revel, 984 F.2d 1164, 1171, 25 U.S.P.Q.2d (BNA) 1601, 1606 (Fed. Cir. 1993) (citing Vas-Cath Inc., 935 F.2d at 1563, 19 U.S.P.Q.2d at 1117)).

311. In re Smith, 481 F.2d 910, 914, 178 U.S.P.Q. (BNA) 620, 623-24 (C.C.P.A. 1973) ("Satisfaction of the description requirement insures that subject matter presented in the form of a claim subsequent to the filing date . . . was sufficiently disclosed at the time of filing so that the prima facie date of invention can fairly be held to be the filing date of the application.").

312. See, e.g., In re Vaeck, 947 F.2d 488, 496, 20 U.S.P.Q.2d (BNA) 1438, 1445 (Fed. Cir. 1991).

313. See, e.g., Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1204, 18 U.S.P.Q.2d (BNA) 1016, 1020 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).

314. Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d (BNA) 1016 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).

315. Id. at 1213-14, 18 U.S.P.Q.2d at 1027.

316. Id. at 1204, 18 U.S.P.Q.2d at 1019. In Amgen, claim seven of the patent at issue reads as follows:

A purified and isolated DNA sequence consisting essentially of a DNA sequence encoding a polypeptide having an amino acid sequence sufficiently duplicative of that of erythropoietin to allow possession of the biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells, and to increase hemoglobin synthesis or iron uptake.Id. Erythropoietin is a hormone which is normally produced by kidney cells and induces the production of red blood cells. See Alberts et al., supra note 56, at 1169-70.

317. Amgen, 927 F.2d at 1212, 18 U.S.P.Q.2d at 1026.

318. Id.

319. Id. at 1213, 18 U.S.P.Q.2d at 1027.

320. Id. at 1213-14, 18 U.S.P.Q.2d at 1027. The Amgen court stated the following:

[D]espite extensive statements in the specification concerning all the analogs of the EPO gene that can be made, there is little enabling disclosure of particular analogs and how to make them. Details for preparing only a few EPO analog genes are disclosed. . . . This "disclosure" might well justify a generic claim encompassing these and similar analogs, but it represents inadequate support for Amgen's desire to claim all EPO gene analogs.

 . . . [W]e do not intend to imply that generic claims to genetic sequences cannot be valid where they are of a scope appropriate to the invention disclosed by an applicant.Id.

321. Id. at 1214, 18 U.S.P.Q.2d at 1027.

322. Amgen, 927 F.2d at 1214, 18 U.S.P.Q.2d at 1027.

323. Id. at 1213, 18 U.S.P.Q.2d at 1027 (citing In re Angstadt, 537 F.2d 498, 502, 190 U.S.P.Q. (BNA) 214, 218 (C.C.P.A. 1976)).

324. Id. at 1213, 18 U.S.P.Q.2d at 1027.

325. Id. at 1213-14, 18 U.S.P.Q.2d at 1027.

326. Id. at 1214, 18 U.S.P.Q.2d at 1027.

327. Amgen, 927 F.2d at 1214, 18 U.S.P.Q.2d at 1028 (quoting In re Fisher, 427 F.2d 833, 839, 166 U.S.P.Q. (BNA) 18, 24 (C.C.P.A. 1970)).

328. Id., 18 U.S.P.Q.2d at 1028.

329. In re Vaeck, 947 F.2d 488, 20 U.S.P.Q.2d (BNA) 1438 (Fed. Cir. 1991).

330. Id. at 490, 20 U.S.P.Q.2d at 1440.

331. Id. at 496, 20 U.S.P.Q.2d at 1445.

332. Id. at 490, 20 U.S.P.Q.2d at 1440.

333. Id. at 496, 20 U.S.P.Q.2d at 1445 (citing In re Fisher, 427 F.2d 833, 839, 166 U.S.P.Q. (BNA) 18, 24 (C.C.P.A. 1970)).

334. Fiers v. Revel, 984 F.2d 1164, 25 U.S.P.Q.2d (BNA) 1601 (Fed. Cir. 1993).

335. Id. at 1166-67, 25 U.S.P.Q.2d at 1602-03. Beta-interferon is a protein that promotes resistance to viral infections when administered to an individual. See id. at 1166, 25 U.S.P.Q.2d at 1603.

336. Id. at 1171-72, 25 U.S.P.Q.2d at 1606.

337. Id. at 1170, 25 U.S.P.Q.2d at 1606.

338. Id. at 1171, 25 U.S.P.Q.2d at 1606.

339. See supra text accompanying notes 336-38; infra text accompanying note 340.

340. Amgen, 927 F.2d at 1214, 18 U.S.P.Q.2d at 1027.

341. See, e.g., Schwartz et al., U.S. Patent No. 5,374,544 (claiming modified skeletal actin promoter sequences with increased expression activity); Foster et al., U.S. Patent No. 5,358,932 (claiming modified human protein C molecules with increased resistance to inactivation by human plasma factors); Kopchick et al., U.S. Patent No. 5,350,836 (claiming growth hormone antagonists with amino acid deletions or substitutions at several locations in the wild-type protein).

342. Ex parte Anderson, 30 U.S.P.Q.2d (BNA) 1866 (B.P.A.I. 1993).

343. Interleukin-3 is a glycoprotein that is believed to be involved in "the growth and differentiation of . . . hematopoietic and lymphoid progenitor cells." Id. at 1867.

344. Id. at 1867. Claim 18 reads as follows: "An isolated DNA sequence encoding a mature human IL-3 protein having a proline residue at position 8 of the mature polypeptide, said protein possessing bone marrow proliferation-inducing activity in a human bone marrow proliferation assay." Id.

345. Id. at 1870. Other than citing the Amgen decision and comparing the claims, the Board did not state the legal grounds for its decision. Id. It should be noted that the application at issue was filed prior to the publication of the Amgen decision. Amgen, 927 F.2d at 1200, 18 U.S.P.Q.2d at 1016; Ex parte Anderson, 30 U.S.P.Q.2d at 1867 ("Patent application of Dirk M. Anderson . . . filed Jan. 20, 1987 . . . .").

346. See supra note 316 for the text of claim seven.

347. The following are two examples of generic claims for genetically engineered inventions from recently issued patents:

Schwartz et al., U.S. Patent No. 5,374,544:

We claim:

1. A DNA sequence comprising:

a promoter region from the 5'-flanking DNA of the chicken [alpha]- actin gene and including a positive cis-acting site;

at least one mutated site in said promoter, wherein said mutated site includes at least three nucleotide substitutions in the naturally occurring DNA sequence and said mutated site promotes the over-expression of a polypeptide functionally linked to said promoter; and

said at least one mutated site occurring in a sequence of ten consecu- tive base pairs adjacent to and including one base pair of said positive cis-acting site wherein said mutation results in formation of a Bgl II restriction enzyme site.Id. at col. 8, ll. 14-29 (emphasis added).

Foster et al., U.S. Patent No. 5,358,932:

What is claimed is:

1. A composition comprising protein C having a light chain and a human-like heavy chain, where said heavy chain contains at least one amino acid substitution as compared to the human activated protein C heavy chain sequence of Fig. 8 and said substitution is within Lys-Met-Thr-Arg-Arg, amino acids 17-21; His-Ser-Arg-Glu-Lys-Gly-Ala, amino acids 146-153; or His-Asn-Gly-Cys-Ser-Glu-Val-Met-Ser-Asn-Met-, amino acids 171-181, wherein said protein C when activated has anticoagulant activity and wherein said one or more amino acid substitutions result in increased resistance to inactivation by human plasma or alpha-1-antitrypsin when compared to naturally occurring activated human protein C.

. . . .

7. The composition according to claim 1, wherein said heavy chain is at least 85% identical to human activated protein C heavy chain.

8. The composition according to claim 7, wherein said heavy chain is at least 95% identical to human activated protein C heavy chain.Id. at col. 23, ll. 33-65 (emphasis added).

348. See infra notes 358-68 and accompanying text for discussion of a recently issued patent in which generic claims for an invention comprising a protein were allowed.

349. See supra note 341. Site-directed mutagenesis involves the use of short, single-stranded DNA molecules, which are generally chemically synthesized, to alter a DNA sequence of a gene. See generally Nickoloff, U.S. Patent No. 5,354,670 (claiming methods for altering DNA sequences via site-directed mutagenesis). The synthesized DNA sequence, commonly referred to as a "primer," has a nucleotide sequence complementary in most respects and capable of hybridizing to the sequence intended to be altered. See id. at col. 4, ll. 18-23; see also supra note 56 (discussing nucleotide pairing and hybridization of complementary nucleic acid molecules). In effect, the complementary sequences of the primer attach to a single strand form of the sequence to be altered and hold the nucleotides which do not match in place. See Sambrook et al., supra note 56, at 15.52. The primer is extended by DNA replication in vitro, resulting in a DNA strand that is identical to the native DNA strand except for the mis-matched region. Id. When this new double-stranded DNA molecule undergoes replication, one of the two molecules produced will contain the alterations included in the primer. See Nickoloff, U.S. Patent No. 5,354,670, col. 4, ll. 34-36.

This technique can be used, for example, to alter the codons of a gene such that one or more specific amino acids are replaced with other amino acids. See Sambrook et al., supra note 56, at 15.81, .95-.104.

350. See supra note 341.

351. See supra note 349.

352. See supra note 349.

353. See, e.g., John D. York et al., Combinatorial Mutagenesis of the Reactive Site Region in Plasminogen Activator Inhibitor I, 266 J. Biological Chemistry 8495 (1991). Gene libraries encoding recombinant proteins can be generated and screened for functional analogs of the natural protein. See id. at 8495. Such a library has been generated and screened for variants of plasminogen activator inhibitor I (PAI-1). Id. at 8496. This gene library consists of DNA molecules that encode PAI-1 proteins in which three amino acids in the polypeptide chain have been randomly substituted with other amino acids. Id. The result is a gene library containing DNA sequences encoding potentially 8000 different PAI-1 derivatives. Id.

Combinatorial mutagenesis, in this instance, was performed by synthesizing DNA complementary to a portion of the PAI-1 coding sequence with nucleotides randomly inserted in the positions encoding the three amino acids of interest. Id. The synthesized DNA sequences were then used to replace "natural" PAI-1 sequences. Id. As a result, a series of DNA molecules were generated encoding PAI-1 analogs with varying amino acids at the positions of the three designated amino acids. Id.

Of approximately 8000 different PAI-1 protein analogs produced and screened for functional activity associated with the natural PAI-1 protein, 135 different PAI-1 variants with activity of the natural protein were identified. Id. at 8497.

354. See infra notes 369-79 and accompanying text.

355. See generally York et al., supra note 353.

356. Schatz et al., U.S. Patent No. 5,338,665 (claiming a method for generating and screening random peptide libraries); Sirotkin, U.S. Patent No. 4,959,312 (claiming an in vitro method of mutagenizing a DNA sequence using random primers).

Mutagenic techniques have been refined to the point where commercially available reagents are available for the modification of DNA sequences. See, e.g., CLONTECH Laboratories, Inc., CLONTECH 95/96 Catalog, Cat. No. K1600-1, 1995 (discussing vector for performing site-directed mutagenesis).

357. See supra note 316 for the text of claim seven, which essentially claims all DNA sequences encoding an amino acid sequence with EPO-like activity.

358. Kopchick et al., U.S. Patent No. 5,350,836. Claim one, for example, reads as follows: "A vertebrate growth hormone in which the amino acid position in said vertebrate growth hormone corresponding to amino acid Gly 119 of bovine growth hormone is deleted or substituted with an amino acid, said vertebrate growth hormone having growth hormone antagonist activity." Id. at col. 25, ll. 11-16.

The generic claims of the `836 patent are not for nucleic acid sequences, but for amino acid sequences. Id. While the specification of the Kopchick patent does not limit the method of production of the growth hormone antagonists to expression from a recombinant nucleic acid sequence, this is indicated as the preferred method for producing the variant proteins. Id. at col. 14, ll. 14-26.

359. Id. at claims 1-26. The inventors constructed several transgenic mice containing altered genes encoding the subject growth hormone antagonists and found that mice expressing these genes were significantly smaller than mice expressing the normal gene. Id. at col. 19, ll. 31-36.

360. Id. The Detailed Description of the Preferred Embodiments states the following:

It is possible to systematically screen for the effect of all possible amino acid substitutions at positions 115 and 119. (There are 202--1 or 399 combinatorial possibilities.) DNA which encodes bGH and is degenerate at these positions, so as to there encode all possible amino acids, or only those with acceptable alpha-helical propensities, is prepared, e.g., by a "dirty bottle" synthesis. Phage are prepared, as taught by Ladner, et al., PCT/US89/03731, W090/02809, which display the mutant bGHs as a domain of a chimeric coat protein. The phage are incubated with a chromatographic support bearing a growth hormone receptor. (For the techniques of isolating growth hormone receptors, see Leung, et al., Nature 330:537 (1987) and Spencer, et al., J. Biol. Chem., 263:7862 (1988)). . . . Bound phage are recovered, amplified and examined to determine the sequence of the mutant bGH (usually by sequencing the corresponding gene in the phage genome). . . . Amino acids which are particularly preferred for screening are the six amino acids spatially nearest bGH's Gly119, that is, Ala122, Leu123, Ile120, Leu116, Asp115, and Glu118.Id. at col. 10, ll. 24-54.

361. Id. at col. 16, l. 1 to col. 17, l. 49. The examples included in the specification describe methods used to generate a variety of mutant growth hormones from recombinant DNA molecules, screening of such mutants for the ability to bind to growth hormone receptor, and the physiological effect that the mutant hormones have on transgenic mice expressing the proteins. Id. at col. 16, l. 1 to col. 25, l. 8.

362. Id. at col. 9, ll. 21-39.

363. Kopchick et al., U.S. Patent No. 5,350,836, col. 20, l. 8.

364. Id. at col. 10, l. 64 to col. 11, l. 51.

365. Id.

366. Id. at col. 10, ll. 26-27.

367. Id. at col. 19, l. 3 to col. 25, l. 4.

368. See, e.g., Leder et al., U.S. Patent No. 4,736,866, col. 5, l. 29 to col. 7, l. 16 (describing the steps of constructing transgenic mice and screening the resulting animals to determine whether they contain the gene of interest).

369. In re Deuel, 51 F.3d 1552, 34 U.S.P.Q.2d (BNA) 1210 (Fed. Cir. 1995).

370. Id. at 1560, 34 U.S.P.Q.2d at 1216.

371. Id. at 1555, 34 U.S.P.Q.2d at 1212. The generic claims at issue, claims four and six, were presented as follows:

4. A purified and isolated DNA sequence consisting of a sequence encoding human heparin binding growth factor of 168 amino acids having the following amino acid sequence: Met Gln Ala . . . [remainder of 168 amino acid sequence].

. . . .

6. A purified and isolated DNA sequence consisting of a sequence encoding bovine heparin binding growth factor of 168 amino acids having the following amino acid sequence: Met Gln Thr . . . [remainder of 168 amino acid sequence].Id. at 1555, 34 U.S.P.Q.2d at 1212 (alterations in original) (first and third omissions in original).

372. Id. at 1560, 34 U.S.P.Q.2d at 1216 (alterations in original) (citing Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1212-14, 18 U.S.P.Q.2d (BNA) 1016, 1026-28 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991)).

373. See supra notes 298-306 and accompanying text.

374. See supra notes 312-28 and accompanying text for a discussion of a generic claim for a DNA sequence and the disclosure necessary for satisfaction of the enablement requirement.

375. Figure 1. (a) shows a hypothetical DNA sequence and the amino acid sequence that it encodes; (b) is a representation of the degenerate DNA sequences which encode the amino acid sequence shown in (a); and (c) shows a series of mis-matched primer sequences that could be used to produce the degenerate DNA sequences of interest. Nucleotides intended to be substituted by each primer are underlined.

376. See Alberts et al., supra note 56, at 23-31.

377. While the number of different molecules in this population would be enormous, see In re Bell, 991 F.2d 781, 784, 26 U.S.P.Q.2d (BNA) 1529, 1531 (Fed. Cir. 1993), if the population of DNA molecules is large enough, it should contain molecules representing all, or nearly all, of the degenerate sequences that encode the amino acid sequence.

378. See Nickoloff, U.S. Patent No. 5,354,670, col. 5, ll. 61-66.

379. Alberts et al., supra note 56, at 106.

380. Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1214, 18 U.S.P.Q.2d (BNA) 1016, 1027 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).

381. Fiers v. Revel, 984 F.2d 1164, 1170, 25 U.S.P.Q.2d (BNA) 1601, 1606 (Fed. Cir. 1993).

382. Id. at 1171, 25 U.S.P.Q.2d at 1606.

383. Utter v. Hiraga, 845 F.2d 993, 998, 6 U.S.P.Q.2d (BNA) 1709, 1714 (Fed. Cir. 1988) ("A specification may, within the meaning of 35 U.S.C. § 112 ¶ 1, contain a written description of a broadly claimed invention without describing all species that claim encompasses." (citing Ralston Purina Co. v. Far-Mar-Co, Inc., 772 F.2d 1570, 1575, 227 U.S.P.Q. (BNA) 177, 179 (Fed. Cir. 1985); In re Rasmussen, 650 F.2d 1212, 1215, 211 U.S.P.Q. (BNA) 323, 326 (C.C.P.A. 1981))).

384. Fiers, 984 F.2d at 1171, 25 U.S.P.Q.2d at 1606.

385. Id.

386. This contention is indirectly supported by a statement made by the Federal Circuit. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1565 n.25, 31 U.S.P.Q.2d (BNA) 1161, 1169 n.25 (Fed. Cir. 1994). In Genentech, referring to the applicants' broad structural and functional definitions of human tissue plasminogen activator, see supra notes 170-78 and accompanying text, the court stated the following:

There may also be a problem with satisfaction of the definiteness and description requirements of 35 U.S.C. § 112 in relation to these other definitions, especially the fourth functional definition. . . . A conclusion that the phrase "human tissue plasminogen activator" is also defined in functional terms would give rise to a definiteness problem because a competitor could not then reasonably determine what DNA sequences are within the scope of the claims and which are not. It would also give rise to a problem with the description requirement because the specification does not even remotely describe all the DNA sequences that encode the proteins within the scope of the functional definition.Genentech, 29 F.3d at 1565 n.25, 31 U.S.P.Q.2d 1169 n.25 (emphasis added) (citing Fiers v. Revel, 984 F.2d 1164, 1171, 25 U.S.P.Q.2d (BNA) 1601, 1606 (Fed. Cir. 1993)). The Genentech situation is quite different from the present one in that the DNA sequences encompassed by a generic claim for all of the sequences encoding one amino acid sequence would be encompassed as a result of their structure, not their function, and the structures of those sequences can be described as shown in Figure 1(b).

387. Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 1214, 18 U.S.P.Q.2d (BNA) 1016, 1027 (Fed. Cir), cert. denied, 502 U.S. 856 (1991).

388. See supra notes 120-38 and accompanying text for a discussion of prior art limitations on patentability.

389. See supra note 347 for examples of recently allowed generic claims for genetically engineered inventions.

390. In Amgen, for example, the Federal Circuit affirmed a district court holding that a generic claim, which had been allowed by the PTO, was invalid. See supra notes 314-28 and accompanying text for a discussion of Amgen.

391. Amgen, 927 F.2d at 1214, 18 U.S.P.Q.2d at 1027.

392. Id. at 1213, 18 U.S.P.Q.2d at 1026.

393. See supra note 1 and accompanying text.

394. See supra note 388 and accompanying text.

395. See supra notes 120-38 and accompanying text for a discussion of prior art limitations on patentability.

396. Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 607 (1950). The United States Supreme Court used these words to describe patents interpreted without application of the doctrine of equivalents. Id.

397. See supra notes 79-192 and accompanying text.

398. Genentech, Inc. v. Wellcome Found. Ltd., 29 F.3d 1555, 1565 n.27, 31 U.S.P.Q.2d 1161, 1169 n.27 (Fed. Cir. 1994).

* The author received a doctoral degree in Biology from Boston College in 1991. The author would like to thank Holliday C. Heine, Ph.D., of Weingarten, Schurgin, Gagnebin & Hayes, for reviewing a draft of this Note and for helpful discussions.