Patenting Biotechnology: Inherent Limits

In recent years, society has witnessed an explosive growth in biotechnology research.1 This growth has been attributed to many factors, among others, the completion of the human genome project, the success of animal cloning, pharmaceutical research, and other notable advances.2 These recent advances promise to further our standard of living by benefiting medicine, agriculture and industry.3 As a result of the scramble to gain proprietary rights over these advances, the biotechnology field has seen phenomenal growth in the number of biotechnology patents that have been filed.4

Biotechnology inventions may include microbes, cell lines, tissue generation, antibody production, proteins, nucleic acids and transgenic multi-cellular organisms.5 These inventions differ from others because the subject matter of such advances may relate to self-replicating entities or life forms not existing in nature.6 As with other classes of technology, inventions in the biotechnology field must be adequately protected to ensure continued innovation.7

Biological inventions possess properties that pose unique challenges to the patent system.8 Among the difficult tasks facing the U.S. Patent and Trademark Office (PTO) is that of encouraging continuing innovation by adequately protecting inventions without granting overly broad patents.9 With this difficult task in mind, a topic that has been a continuing focus of the biotechnology industry is the standard of examination applied by the PTO to biotechnology inventions.10

This article examines the standards employed by the PTO in examining biotechnology patent applications. Specifically, the evolution of the heightened standard of enablement and written description requirements will be discussed. Part I of this paper provides an overview of the U.S. patent system; discussing essential background topics such as the constitutional basis for the patent system, subject matter limitations and the statutory requirements for patenting as applied to biotechnology. Part II briefly summarizes patent prosecution procedures before the PTO. Part III and IV follow, discussing the enablement and written description requirements of 35 U.S.C. § 112 respectively. Prior to conclusion, Part V will provide analysis of the issues confronting inventors prosecuting biotechnology patents.

The protections afforded to biotechnology inventions arise from the Constitution.11 Pursuant to the U.S. Constitution, Congress shall have the power “To promote the Progress of Science . . . by securing for limited times to . . . Inventors the exclusive Right to their . . . Discoveries.”12 This mandate was most recently implemented through the Patent Act of 1952.13 The general policy behind the U.S. patent system is to promote the progress of science by offering to inventors limited monopolies over their inventions in exchange for public disclosure.14 Unlike many foreign patent systems, the U.S. system awards a patent to the first person to invent.15 Under this system, society grants the inventor a limited patent monopoly over her invention for a period of twenty years from the date the patent application is filed.16 The patent allows the inventor the right to exclude all others from making, using, selling, offering for sale or importing the patented invention.17 In return, the public receives full disclosure of a new and useful invention that enters the public domain after the patent term expires.18

For an invention to be patentable, it must be (1) patentable subject matter, (2) useful, (3) novel, (4) non-obvious, and (5) sufficiently enabled and described.19 The first issue that must be addressed is whether the biotechnology patent consists of patentable subject matter within the meaning of 35 U.S.C. § 101.20 Pursuant to section 101, utility patent protection is available for anyone who “invents or discovers any new and useful [1] process, [2] machine, [3] manufacture, or [4] composition of matter.”21 Biotechnology patents usually fall within the article of manufacture or composition of matter categories.22 While patents may be obtained for DNA, proteins, antibodies, transgenic microorganisms, viruses, plants and animals, specifically excluded from the realm of patentable subject matter are laws of nature, mathematical and scientific formulas, abstract ideas, naturally occurring objects, and human life.23

Assuming the biotechnology invention consists of patentable subject matter, there are three statutory subject matters that the invention must meet.24 Thus, an inventor will only obtain a patent if their invention is (1) useful,25 (2) novel,26 and (3) non-obvious 27. Please note that a discussion of the novelty and non-obvious criteria is beyond the scope of this article.

In order to be patentable, an invention must be useful.28 Although this requirement does not require an invention to be commercially useful, the invention must be of some measurable benefit; more than a mere curiosity.29 Often, the written description and enablement requirements will sufficiently disclose an invention’s usefulness.30 However, a practical utility is not always evident in a biotechnology invention.31 For example, the creation of a new microorganism or cell line may not necessarily teach the utility thereof.32 This line of reasoning was adopted in Brenner v. Manson,33 where the court held that merely producing something that is the object of scientific research is insufficient to justify the grant of a patent.34 Unless and until a biotechnology invention is refined and developed to the point where a specific benefit exists, the usefulness of the invention is unproven.35

The courts have applied a more stringent test for usefulness in biotechnology patents, requiring a biotechnology patent to have a “practical utility.”36 Applying this requirement, PTO examiners have rejected biotechnology patents that do not disclose a therapeutic value.37 Despite this nuance, a single accepted utility is sufficient to justify the claims of a biotechnology invention.38

Patent prosecution is the process by which an inventor obtains a patent from the PTO.39 Once the inventor files an application for a patent,40 the time and effort required to prosecute a patent will vary immensely from case to case.41 During this process, 35 U.S.C. § 112 provides that an inventor shall provide a specification containing (1) a written description of the invention, (2) an enabling disclosure, and (3) the best mode for carrying out the invention.42 Case law has made clear that the requirements for a written description are separate and distinct from the enabling disclosure.43 A separate written description requirement is required to ensure that the applicant was in possession of the claimed invention at the time of filing.44 The enablement requirement is distinct from this, and mandates that a specification teach a person skilled in the art to which the invention pertains how to make and use the full scope of the invention without undue experimentation.45 Current trends of the Federal Circuit require a heightened enablement and written description requirement when prosecuting biotechnology applications.46

To be enabling under 35 U.S.C. § 112, a patent must contain a disclosure that enables one skilled in the art to make and used the claimed invention.47 Recent biotechnology enablement cases presents common themes: (1) that the public should not be required to carry out “undue” experimentation to put an invention into practice; (2) whether experimentation is undue is established by weighing several factors, such as the predictability of the art; (3) biotechnology is inherently unpredictable; and (4) the highly unpredictable nature of biotechnology mandates a heightened enablement disclosure.48 Where a claim is overly broad, and experimentation necessary to practice the invention is undue, a patent will fail for lack of enablement.49 “That some experimentation is necessary does not preclude enablement; the amount of experimentation, however, must not be unduly extensive.”50

Generally, a patent claim complies with the enabling requirements if a reasonable amount of experimentation is necessary so long as such experimentation is not undue.51 In In re Wands,52 the court set forth several factors to determine whether experimentation was undue.53 The determination of what constitutes undue experimentation is measured by the standard of reasonableness,54 and no single factual determination will render experimentation undue.55 Rather, that conclusion is reached by weighing several factors, such as (1) the quantity of experimentation necessary, (2) the guidance provided by the specification, (3) the availability of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the breadth of the claims, and (8) the predictability or unpredictability of the art.56

Among these factors, the predictability of the relevant art is particularly relevant in considering the sufficiency of enabling disclosures for biotechnology applications.57 While mechanical arts are considered predictable due to permissible reliance of established scientific and mathematical laws, biological arts are considered unpredictable because scientists are unable to precisely predict how simple changes in temperature, pressure, and pH will effect biological processes.58 Consequently, in biotechnology inventions, the scope of enablement must be more detailed as the level of unpredictability of the invention rises.59

Biotechnology inventions are traditionally considered more unpredictable than are the mathematically based sciences.60 The unpredictability of biotechnology was acknowledged in Enzo Biochem v. Calgene, Inc.61 In Enzo Biochem, the evidence established that Enzo’s patent for anti-sense technology was insufficiently enabled.62 There, the claims at issue taught the application of anti-sense technology in regulating genes in the prokaryote e-coli.63 However, the claims were drafted to encompass application of anti-sense technology in both eukaryote and prokaryote cells.64 The Federal Circuit held that Calgene’s FlavrSavr tomato did not infringe Enzo’s patents because those patents were invalid.65 Because anti-sense technology and biotechnology in general was a “highly unpredictable technology” and “the amount of experimentation required to adapt the practice of anti-sense from e-coli to [other cells] was quite high,” the overly broad claims were declared invalid.66
¶15

Enablement of a biotechnology invention fails when a disclosure fails to provide scientific starting materials or any of the conditions under which the process can be carried out, resulting in undue experimentation.67 In Genentech v. Novo Nordisk of North America, 68the evidence established that plaintiff had failed to provide a sufficient enabling disclosure for a biotechnology invention.69 The invention at issue in that case involved a method of producing a protein consisting essentially of human growth hormone.70 Failure of enablement was cited as the reason for holding plaintiff’s patent invalid, however, because the specification did not describe in any detail how to make the hormone using the stated process.71 Because reaction conditions required to produce the hormone were lacking, undue experimentation was required and the enablement provision failed.72

Moreover, the specification must teach those skilled in the art how to make and use the invention as broadly as claimed, without undue experimentation.73 In Amgen, Inc. v. Chugai Pharmaceutical Co.,74 the Federal Circuit held Amgen’s patent invalid for failure to enable.75 There, the patents involved the production of human erythropoietin (EPO), a protein consisting of 165 amino acids that stimulates the production of red blood cells.76 The lower court determined that substitution of just one of the 165 amino acids in the patented EPO could result in approximately 3,600 different forms of EPO.77 Evidence adduced at trial established that 50 to 80 of these derivatives might not serve the same function as the patented EPO.78 With such a vast number of possible derivatives, some expressing the desired characteristics and others not, the court held that the enabling disclosure was insufficient to encompass the all-encompassing claims.79 While the court believed the amount of experimentation necessary was not a controlling factor, instead holding that Amgen’s enabling specifications did not support such an overly broad claim; it is likely that had Amgen been able to fully explain which derivatives would express the desired results, and the composition of their amino acid chains, the patent may have been held valid because the amount of experimentation necessary would have been acceptable.80

Thus, the PTO and Federal Circuit subject biotechnology to a heightened standard of enablement due to the unpredictability of the art. In In re Vaeck,81 for example, the Federal Circuit rejected applicant’s claim as not enabled due to the unpredictability of the microbiology of bacteria.82 The patent in that case involved the production of Bacillus proteins within a host cyanobacteria.83 The claimed invention produced a protein toxic to insects such as mosquitoes and black flies within their cyanobacteria food source.84 The court held that the applicant did not sufficiently enable his invention, however, because there were over 150 genera of cyanobacteria.85 The narrow disclosures in the application, which provided only nine genera and two particular species of bacillus,86 in conjunction with the “relatively incomplete understanding of the biology of cyanobacteria” were factors considered in denying the patent.87 The court held that even though the patent applicants were not required to disclose every species encompassed by their claim, even in such an unpredictable art, where the claimed genus of cyanobacteria represented a diverse and relatively poorly understood group of microorganisms, “the required level of disclosure [was] greater than . . . the disclosure of an invention involving a ‘predictable’ factor such as a mechanical or electrical elements.”88

The Federal Circuit has similarly applied the written description requirement in a manner that raises the patentability bar.89 To fulfill this requirement, “the patent specification must clearly allow a person or ordinary skill in the art to recognize that the inventor invented what is claimed.”90 Generally, a separate written description requirement is designed to ensure that the applicant was in possession of the claimed invention at the time the application was filed.91 Whereas the enabling requirement teaches one skilled in the art how to make the invention, the written description serves to put the public in possession of what the applicant claims as the invention.92

The unique nature of biotechnology and its unpredictability necessitates a heightened written description requirement.93 Issues involving the written description requirement in biotechnology frequently arise in the context of continuation application where an inventor seeks to be entitled to the filing date of an earlier application.94 In such cases, claims not presented in the original application are presented thereafter, and the applicant seeks the benefit of the earlier filing date for the later filed application.95 In In re Ruschig,96 the court applied the written description requirement to strike claims in a continuation application.97 In doing so, the court evaluated whether the original application, when filed, would disclose to one skilled in the art that the inventor had actually invented and was in possession of the later claims as of the original filing date.98 Thus, in that case, the court effectively transformed the written description requirement into a means for evaluating claims contained in a continuation application.99
¶20

More recently, in Vascath v. Mahurkur,100 the court followed this reasoning, using the written description requirement to prevent an inventor from overreaching by requiring that he disclose his invention as originally filed in such detail as to enable a future skilled person to determine whether later filed claims were encompassed in the original invention.101 There, the applicant (Mahurkur) filed an original application for his catheter technology.102 Years later, the applicant filed a continuation application claiming the benefit of the filing date of the earlier application.103 The court found the written description sufficient to entitle the applicant to the earlier filing date, holding that “the applicant must . . . convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.”104 Thus, since the earlier application encompassed the later, showing that the applicant was in possession of the invention at the time of the original filing date, the written description requirement was met.105 However, the original application need not contain an identical disclosure of the later claims.106 The question is whether the original application would have reasonably conveyed to one skilled in the art that the applicant invented the later claimed subject matter at the time of the original filing.107

The Federal Circuit has correctly applied the enablement provision of 35 U.S.C. § 112 to prevent inventors from obtaining and enforcing overly broad biotechnology patent rights.108 Permitting an inventor to obtain and enforce overly broad patent where undue experimentation would be necessary would compromise the fundamental purposes of the patent system.109 The Federal Circuit should continue applying a heightened standard to ensure that an inventor gains no rights to technology that he did not invent through broadly written claims.110 If these practices were permitted, the public would not gain the benefit of disclosure of the new and useful invention in exchange for its grant of a limited monopoly to the inventor.111 Furthermore, overly broad claims would chill scientific research and development.112 Permitting overly broad and non-enabled claims would create a disincentive for researchers to invest their time, capital, and resources in developing new biotechnology out of fear of being blocked by a previous existing meritless broad patent purporting to encompass what it did not really invent.113

As for the written description requirement, the utility of the stricter standard is probably best illustrated by reference to DNA.114 Since DNA structures contain four bases in a plethora of combinations, with one change altering the whole strain, the Federal Circuit has stated that an adequate written description of DNA requires more than a mere statement that it is part of an invention and the method for isolating it.115 What is required in such cases is a description of the DNA itself, since without the precise description of the sequence of constituent bases, it is impossible to establish that the inventor actually invented the DNA he claims.116

Critics assert that strict application of the written description and enablement requirements may also reduce the incentive for scientific research by depriving patentees the opportunity to fully benefit from their research.117 This position argues that the current requirements in biotechnology reduce the value of the patent by requiring very narrow claims; claims that allow competitors to easily avoid infringement liability through minor variations in similar patents.118 Nevertheless, these shortcomings are generally considered preferable to granting overly broad patents.119

The enablement and written description requirements promote several policies underlying the patent system. The requirements seek to maintain an optimal equilibrium between granting inventors the benefits of a patent without removing from the public domain that which falls beyond such invention. The issue is primarily one of breadth. The requirements prohibit an inventor from claiming an invention that is overly broad. Permitting overly broad patents would frustrate the intent of the patent system by resulting in a norm whereby the public would grant an exclusive monopoly in exchange for a patent that is overly broad, inadequately described, and therefore less useful to society.
¶25

As with patents in general, the enabling requirement requires that a person skilled in the art not be required to perform undue experimentation when practicing the invention. The Federal Circuit has measured undue experimentation by reference to several factors. Of particular relevance to the prosecution of biotechnology patents is the predictability of the relevant art. The unpredictable nature of biological inventions mandates a heightened enabling disclosure. Practicing a biotechnology invention may present more difficulties than other, more mechanical arts, because the subject matter is somewhat more imprecise. In biological processes in particular, minute changes in starting materials and conditions such as light, heat, chemical concentrations, and the like may dramatically alter the intended result. Thus, as a prerequisite to patenting a biotechnology invention, the Federal Circuit generally requires enabling disclosures to be very precise. If such a heightened standard were not the norm, patents that were overly broad would inevitably result. Allowing overly broad patents would compromise the policies underlying the patent system, by giving to an inventor protection for that which he did not invent.

Furthermore, the Federal Circuit generally requires a heightened written description requirement as well due to the unpredictability of biotechnology. The intent behind the written description requirement is to ensure that an inventor was actually in possession of the claimed invention at the time of filing. Cases litigating the written description requirement commonly arise in the context where an inventor files a continuation application and seeks to entitle the continuation to the filing date of a parent. In such cases, the courts will looks to whether the parent application encompasses the continuation, displaying to a person skilled in the relevant art that the inventor in fact invented the later claims at the time the parent was initially filed.

The enabling and written description requirements require heightened standards in biotechnology prosecutions if the patent system is to operate at optimum health. By applying such standards to an unpredictable art such as biotechnology, the Federal Circuit has assured that the public will continue to gain the knowledge and innovation of inventors in exchange for the grant of a valuable exclusive monopoly.

[1]	John R. Wetherell, Jr., U.S. Biotechnology Patent Concepts, at http://cbdn.ca/patent.htm (last visited Mar. 9, 2001).
[2]	Margaret Sampson, The Evolution of the Enablement and Written Description Requirements under 35 U.S.C. §112 in the area of Biotechnology, 15 Berkeley Tech. L. J. 1233, 1234 (2000).
[3]	Id.
[4]	See Wetherell, supra note 1.
[5]	Dean Nakamura, Biotechnology Bits and Pieces, at http://www.sughrue.com/articles/genetic/deanbits.htm (last visited Mar. 10, 2001).
[6]	Id.
[7]	See Sampson, supra note 2, at 1234.
[8]	Id.
[9]	Id.
[10]	See Biotechnology and United States Patent Practice, at wysiwyg://32/http://www.ladas.com/GUIDES/BIOTECH/Biotechnology.USA.htr (last visited Mar. 9, 2001) [hereinafter Ladas].
[11]	Nakamura, supra note 5.
[12]	U.S. Const. art. I, § 8, cl. 8.
[13]	Patent Act of 1952, 35 U.S.C. §§ 1-376 (1994 & Supp. II 1996).
[14]	See Sampson, supra note 2, at 1234.
[15]	Id.
[16]	35 U.S.C. § 154 (1994 & Supp. II 1996).
[17]	35 U.S.C. § 271(a) (1994 & Supp. II 1996).
[18]	Sampson, supra note 2, at 1235.
[19]	See Wetherell, supra note 1.
[20]	Id.
[21]	35 U.S.C. § 101 (1994 & Supp. II 1996).
[22]	Nakamura, supra note 5; Wetherell, supra note 1.
[23]	Wetherell, supra note 1.
[24]	Id.
[25]	35 U.S.C. § 101.
[26]	35 U.S.C. § 102 (1994 & Supp. II 1996).
[27]	35 U.S.C. § 103 (1994 & Supp. II 1996).
[28]	35 U.S.C. § 101; Ladas, supra note 10.
[29]	See Ladas, supra, note 10.
[30]	Nakamura, supra note 5.
[31]	Id.
[32]	Id.
[33]	383 U.S. 519 (1966).
[34]	Ladas, supra note 10.
[35]	Id.
[36]	Nelson v. Bowler 626 F.2d 853 (C.C.P.A. 1980); Ex Parte Deuel, 51 F.3d 1552 (Fed. Cir. 1995); Ladas, supra note 10.
[37]	Ladas, supra note 10.
[38]	Id.
[39]	Robert P. Merges et. al., Intellectual Property in the New Technological Age 134 (2000).
[40]	See 35 U.S.C. § 111 (1994 & Supp. II 1996) (requiring a patent application to be made, or authorized to be made, by the inventor).
[41]	Merges, supra note 10, at 134.
[42]	35 U.S.C. § 112 (1994 & Supp. II 1996).
[43]	Ladas, supra note 10.
[44]	Sampson, supra note 2, at 1252.
[45]	Id. at 1239.
[46]	Id. at 1235.
[47]	Atlas Powder Co. v. E.I. DuPont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984).
[48]	Ladas, supra note 10.
[49]	See generally In re Goodman, 11 F.3d 1046, 29 U.S.P.Q.2d 2010 (Fed. Cir. 1993).
[50]	Id. at 1052.
[51]	See Enzo Biochem Inc. v. Calgene, 188 F.3d 1362 (Fed. Cir.1999).
[52]	858 F.2d 731 (Fed. Cir. 1988).
[53]	Id.
[54]	In re Wands, 858 F.2d at 736.
[55]	Id.
[56]	Id.
[57]	Sampson, supra note 2, at 1240.
[58]	See In re Fisher, 427 F.2d 833, 839 (C.C.P.A. 1969).
[59]	Sampson, supra note 2, at 1240.
[60]	See generally In re Fisher, 427 F.2d at 833.
[61]	188 F.3d 1362, 52 U.S.P.Q.2d 1129 (Fed. Cir. 1999).
[62]	Id. at 1381.
[63]	Id. at 1367-68.
[64]	Id. at 1372.
[65]	Id. at 1381.
[66]	Enzo Inc., 927 F.2d at 1372.
[67]	Genentech, Inc. v. Novo Nordisk of North America, Inc., 108 F.3d 1361, 1366, 42 U.S.P.Q.2d 1001 (Fed. Cir. 1997).
[68]	Id.
[69]	Id. at 1368.
[70]	Id. at 1363.
[71]	Id. at 1365.
[72]	Genentech, 108 F.2d at 1365.
[73]	In re Goodman, 11 F.3d at 1050.
[74]	927 F.2d 1200, 18 U.S.P.Q.2d 1016 (Fed. Cir. 1991).
[75]	Id. at 1203.
[76]	Id.
[77]	Id. at 1212.
[78]	Id.
[79]	Amgen, Inc. 927 F.2d at 1212.
[80]	See generally id.
[81]	947 F.2d 488, 496, 20 U.S.P.Q.2d 1438 (Fed. Cir. 1991).
[82]	Id.
[83]	Id. at.489.
[84]	Id. at 490.
[85]	Id. at 495.
[86]	In re Vaeck, 947 F.2d at 490.
[87]	Id. at 490.
[88]	Id. at 496. Emphasis added.
[89]	Arti K. Rai, Intellectual Property Rights in Biotechnology: Addressing New Technology, 34 Wake Forest L. Rev. 827, 834 (1999).
[90]	The Gentry Gallery, Inc. v. The Berkline Corp., 134 F.3d 1473 (Fed. Cir. 1998).
[91]	Sampson, supra note 2, at 1252 citing In re Ruschig, 343 F.2d 965 (C.C.P.A. 1965).
[92]	Id.
[93]	Id. at 1259.
[94]	Kenneth D. Sibley, The Law and Strategy of Biotechnology Patents 131 (1994).
[95]	Vas-Cath Inc. v. Mahurkur, 935 F.2d 1555 (Fed. Cir. 1991).
[96]	379 F.2d 990 (C.C.P.A. 1967).
[97]	Id. at 991; Janice M. Mueller, The Evolving Application of the Written Description Requirement to Biotechnological Inventions, 13 Berkeley Tech. L. J. 615, 621 (1998).
[98]	In re Ruschig, 379 F.2d at 995, Mueller, supra note 96, at 621.
[99]	Mueller, supra note 96, at 621.
[100]	935 F.2d 1555 (Fed. Cir. 1991).
[101]	Id. at 1561, Mueller, supra note 96, at 621.
[102]	935 F.2d at 1559.
[103]	Id.
[104]	Id. at 1563-64.
[105]	See generally id.
[106]	Sibley, supra note 93, at 131.
[107]	Id.
[108]	Sampson, supra note 2, at 1246.
[109]	Id.
[110]	Id. at 1247.
[111]	See generally id.
[112]	Id.
[113]	Sampson, supra note 2, at 1248.
[114]	Id. at 1259.
[115]	Fiers v. Revel, 984 F.2d 1164, 1171 25 U.S.P.Q.2d 1601 (Fed. Cir. 1992); Sibley, supra note 93, at 132.
[116]	Sibley, supra note 93, at 132; Sampson, supra note 2, at 1259.
[117]	Sampson, supra note 2, at 1262.
[118]	Id.
[119]	Id.