Ex Parte Harris et alDownload PDFBoard of Patent Appeals and InterferencesApr 3, 200910119546 (B.P.A.I. Apr. 3, 2009) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte J. MILTON HARRIS, FRANCESCO MARIA VERONESE, PAOLO CALICETI and ODDONE SCHIAVON __________ Appeal 2009-1274 Application 10/119,546 Technology Center 1600 __________ Decided:1 April 3, 2009 __________ Before ERIC GRIMES, RICHARD M. LEBOVITZ, and STEPHEN WALSH, Administrative Patent Judges. WALSH, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to an essentially pure polymer. The Patent Examiner rejected the claims as 1 The two-month time period for filing an appeal or commencing a civil action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date shown on this page of the decision. The time period does not run from the Mail Date (paper delivery) or Notification Date (electronic delivery). Appeal 2009-1274 Application 10/119,546 indefinite and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse on indefiniteness and affirm on obviousness. STATEMENT OF THE CASE The invention relates to derivatives of polyethylene glycol, abbreviated “PEG,” that are used to modify the characteristics of other molecules and of surfaces. (Spec. 1:8-12.) PEG was known to enhance the solubility and stability of therapeutic proteins like enzymes. (Id. at 2:10-20.) Appellants’ invention is a branched or multi-armed PEG derivative that can be prepared without toxic linkages or potentially toxic fragments. (Id. at 11:16-23.) “Relatively pure polymer molecules of high molecular weight can be created.” (Id. at 11:23-24.) After the PEG derivative or polymer molecule is synthesized, it can be coupled to a molecule such as a protein or enzyme or to a surface. (Id. at 12:1-3.) Claims 96-109, 111, 112, 114-124, and 133 are on appeal.2 The Examiner rejected the claims as follows: • claims 96-109, 111, 112, 114-124, and 133 under 35 U.S.C. § 112, ¶ 2, as indefinite because the term “essentially pure” is uncertain as to its meaning and scope; and • claims 96-109, 111, 112, 114-124, and 133 under 35 U.S.C. § 103(a) as obvious over the combined teachings of Martinez,3 Sartore,4 Veronese,5 Yoakum,6 and Abuchowski.7 2 Claims 125-132 are also pending but have been withdrawn from consideration by the Examiner. (App. Br. 5.) 3 U.S. Patent No. 5,643,575, issued Jul. 1, 1997. 2 Appeal 2009-1274 Application 10/119,546 The claims have not been argued separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 96 is representative and reads as follows: 96. An essentially pure water-soluble polymer having the structure: polya—P │ R—C—Z │ polyb—Q wherein: R is a nonreactive moiety, Z is a moiety comprising a reactive site, polya and polyb are each independently a nonpeptidic polymer, and P and Q each comprise a nonreactive linker absent an aromatic ring or ester group. FINDINGS OF FACT 1. The original Specification and claims did not use the phrase “essentially pure.” 4 Luciana Sartore et al., Enzyme Modification by MPEG with an Amino Acid or Peptide as Spacer Arms, 27 APPL. BIOCHEM. BIOTECHNOL. 45-54 (1991). 5 F.M. Veronese et al., Preparation and Properties of Monomethoxypoly(Ethylene Glycol)-Modified Enzymes for Therapeutic Applications, in Poly(Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications 127-37 (J. Milton Harris ed., Plenum Press, New York, 1992). 6 U.S. Patent No. 4,650,909, issued Mar. 17, 1987. 7 Abraham Abuchowski et al., CANCER THERAPY WITH CHEMICALLY MODIFIED ENZYMES. I. ANTITUMOR PROPERTIES OF POLYETHYLENE GLYCOL-ASPARAGINASE CONJUGATES, 7 CANCER BIOCHEM. BIOPHYS. 175-86 (1984). 3 Appeal 2009-1274 Application 10/119,546 2. Appellants’ “Summary of the Invention” states: “[r]elatively pure polymer molecules of high molecular weight can be created.” (Spec. 11:23-24.) 3. The “Summary of the Invention” also states: “[t]hese purifiable, high molecular weight, monofunctional compounds have many uses.” (Spec. 15:24-25.) 4. The “Detailed Description” summarizes two chromatographic purifications of an example polymer as follows: “For both methods of purification, purified mPEG-disubstituted lysine of molecular weight 10,000, titrated with NaOH, showed that 100% of the carboxyl groups were free carboxyl groups. These results indicate that the reaction was complete and the product pure.” (Spec. 23:33 – 24:2.) Martinez 5. Martinez described branched polymers, that include polymers comprising PEG, “useful in extending the in vivo circulating life of biologically active materials.” (Col. 1, ll. 6-8.) 6. Biologically active materials to be conjugated to the polymers included proteins and enzymes. (Col. 2, ll. 25-30.) 7. According to Martinez, the branching of the polymers gives an advantage that contrasts with the “conventional polymer conjugates.” (Col. 2, ll. 43-47.) 8. Martinez taught that “[a]fter synthesis, the activated branched polymers can be purified by conventional methods and reacted with biologically active materials . . . .” (Col. 7, ll. 12-15.) 4 Appeal 2009-1274 Application 10/119,546 9. Martinez taught that “[f]ollowing the reaction, the conjugate is recovered and purified such as by diafiltration, column chromatography, combinations thereof, or the like.” (Col. 9, ll. 27- 30.) Sartore 10. Sartore disclosed that polyethylene glycol was finding rapidly expanding use in biomedical applications for derivatizing enzymes of therapeutic value. (46:1st para.) 11. Sartore described modifying arginase, an enzyme, with MPEG (monomethoxy polyethylene glycol). (48:2nd para.) 12. Sartore described purifying the modified arginase from excess MPEG and products of the reaction with column chromatography. (48:2nd para.) Veronese 13. Veronese taught that the “therapeutic value of enzymes as drugs would be considerably increased if drawbacks such as immunogenicity and antigenicity, rapid clearance from circulation . . . were overcome.” (127:1st paragraph.) 14. According to Veronese, “[n]atural or artificial polymers are being used for surface enzyme modification” including MPEG. (127:2nd paragraph.) 15. Veronese described removing unreacted MPEG from the modified enzyme by gel filtration [a form of column chromatography]. (129:4th paragraph.) Yoakum 5 Appeal 2009-1274 Application 10/119,546 16. Yoakum described a purification process to produce improved polyethylene glycol (PEG) to be used in cell fusion. (Abstract.) 17. Yoakum’s purification process removed toxic elements from the known and impure PEG. (Abstract.) 18. According to Yoakum, PEG was known to include aldehydes and ketones that were cytotoxic because they lyse cells. (Col. 2, ll. 53- 59.) 19. Yoakum’s purification system used ion exchange columns [a form of column chromatography] to separate the toxins from PEG. (Col. 3, l. 65 – col. 4, l. 13.) 20. Yoakum’s purified PEG was suitable for use in human cell genetic transfection. (Col. 1, ll. 10-13.) Abuchowski 21. According to Abuchowski, “L-Asparaginase is commonly used in the treatment of acute leukemias.” (175:1st para.) 22. Abuchowski reported that attaching PEG to asparaginase, an enzyme, produced conjugates that were “active, stable, without significant immune response, and with greatly extended plasma half-lives in mice.” (Abstract.) 23. Abuchowski prepared SS-PEG (methoxypolyethylene glycolyl succinimidyl succinate) for conjugation to asparaginase. (176:2nd para.) 24. The SS-PEG was “examined for homogeneity and absence of low molecular weight components by HPLC using the Waters apparatus 6 Appeal 2009-1274 Application 10/119,546 and the Varian G-3000 PW column [a form of column chromatography].” (176:2nd para.) 25. After reacting SS-PEG with asparaginase, the unbound SS-PEG was removed by dialysis. (Para. bridging 176-177.) DEFINITENESS The Issue The Examiner’s position is that the claim term “essentially pure” is not defined in the Specification and the phrase “would be uncertain as to materials permitted and excluded in combination with the claimed polymer.” (Ans. 4 and 9-10.) Appellants contend that the Specification’s description of purification and characterization of the claimed polymer makes the meaning of “essentially pure” clear to those of skill in the art. (App. Br. 11.) The issue with respect to this rejection is whether those of ordinary skill in the art of water soluble polymers would understand what “essentially pure” means in light of Appellants’ specification? Principles of Law Relating to Definiteness The burden of precise claim drafting rests squarely upon the applicant. In re Morris, 127 F.3d 1048, 1055 (Fed. Cir. 1997). “‘It is axiomatic that, in proceedings before the PTO, claims in an application are to be given their broadest reasonable interpretation consistent with the specification, . . . and that claim language should be read in light of the specification as it would be 7 Appeal 2009-1274 Application 10/119,546 interpreted by one of ordinary skill in the art.’” In re Bond, 910 F.2d 831, 833 (Fed. Cir. 1990). When a word of degree is used without definition, the question is “whether one of ordinary skill in the art would understand what is claimed when the claim is read in light of the specification.” Seattle Box Co., Inc. v. Indus. Crating & Packing, Inc., 731 F.2d 818, 826 (Fed. Cir. 1984) (affirming district court determination that “substantially equal to” was not indefinite). Prior art references may be “indicative of what all those skilled in the art generally believe a certain term means ... [and] can often help to demonstrate how a disputed term is used by those skilled in the art.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1584 (Fed. Cir. 1996). Analysis of the Definiteness Issue According to Appellants, one of ordinary skill in the art would understand the phrase “essentially pure” as meaning the kind or level of purity described in the Specification. (App. Br. 9.) Appellants argue that examples of branched polymers described in the Specification were essentially pure “as evidenced by the NMR and chromatographic data showing that the branched polymers were free from detectable amounts of unreacted organic reactants, and side-products, as well as polymer intermediates and side products.” (App. Br. 10.) The secondary references cited in the obviousness rejection recognize removal of unreacted material and side-products as criteria of purity, and we weigh that as evidence supporting Appellants’ construction. (FF12; FF15; FF24; FF25.) See Vitronics, 90 F.3d at 1584. 8 Appeal 2009-1274 Application 10/119,546 The Examiner was unpersuaded, and noted instead that “[b]eing 100% pure is different from being essentially pure.” The Examiner concluded that the amounts and kinds of impurities tolerated by “essentially” should have been described. (Ans. 9-10.) We agree with the Examiner that 100% pure is different from “essentially” pure. However, we do not agree that Appellants were required to specify a numerical “amount” of tolerable impurities to achieve definiteness. The terms “about” and “substantially” are commonly used in patent terms to “‘avoid a strict numerical boundary to the specified parameter.’” Ecolab, Inc. v. Envirochem, Inc., 264 F.3d 1358, 1367 (Fed. Cir. 2001) (citation omitted). Appellants are using “essentially” in a similar way. Appellants here described their polymers as purifiable (FF2), gave examples of purification, and described the product as pure (FF4). As to the kinds of impurities that the Examiner concluded should have been described, Appellants directed attention to the Specification’s NMR and chromatography results. According to Appellants, those results evidence purity that is free from detectable amounts of unreacted organic reactants and side-products, as well as polymer intermediates and side-products. (App. Br. 10.) We conclude that a person of ordinary skill in the art would understand that “essentially pure” means the kind and degree of purity described in the Specification: free from detectable amounts of unreacted organic reactants and side-products, as well as polymer intermediates and side-products. We conclude that Appellants’ claims meet the Seattle Box criterion for definiteness. Seattle Box, 731 F.2d at 826 (“one of ordinary 9 Appeal 2009-1274 Application 10/119,546 skill in the art would understand what is claimed when the claim is read in light of the specification”). The Examiner also argues that the term is used “at a point of novelty, and in such case the meaning and scope of ‘essentially pure’ must be precise.” (Ans. 10.) The second paragraph of § 112 is “essentially a requirement for precision and definiteness of claim language.” In re Borkowski, 422 F.2d 904, 909 (CCPA 1970) (emphasis in original). To the extent the Examiner suggests a numeric constraint is required to achieve precision, that requirement would be inconsistent with precedent interpreting terms of degree. E.g., Playtex Products, Inc. v. Procter & Gamble Co., 400 F.3d 901, 907 (Fed. Cir. 2005) (requiring a numeric constraint on terms of degree such as “substantially” contradicts precedent interpreting such terms); see also In re Marosi, 710 F.2d 799, 802 (CCPA 1983) (number not needed to define “essentially free” of impurities). In the context of a given specification, a term of degree based on a verbal description can be precise, when construed “in light of the specification as it would be interpreted by one of ordinary skill in the art.” Bond, 910 F.2d at 833. If “essentially pure” is a point of novelty or nonobviousness for Appellants’ claims, the claims can be compared to the prior art to decide those questions. OBVIOUSNESS The Obviousness Issue The Examiner’s position is that Martinez taught branched polymers having the structure claimed and taught that the polymers can be purified by conventional methods before conjugation. (Ans. 6.) The Examiner contends 10 Appeal 2009-1274 Application 10/119,546 that one of skill in the art would have found it obvious to purify Martinez’s polymers by conventional purification methods disclosed in Yoakum, Sartore, Veronese, and Abuchowski. (Ans. 6.) The Examiner found that a person of ordinary skill in the art at the time of the invention would have been motivated to purify Martinez’s polymers because the in vivo uses Martinez described would “require purification sufficient to make the mPEG disubstituted lysine pure enough for in vivo use.” (Ans. 6-7.) Appellants admit that “Martinez [taught] branched polymer structures of the type embodied by the present claims.” (App. Br. 13.) Appellants contend that “Martinez merely suggests that the polymers described therein can be purified,” but that Martinez did not recognize the problems associated with purification. (Id. at 13-14, emphasis in original.) In Appellants’ view, “[t]he real question then is, would one looking at Martinez, in the absence of the Appellant’s disclosure, be motivated to not only modify Martinez, but to successfully arrive at the essentially pure polymers of the Appellant’s claims.” (Id. at 19.) Appellants contend that the disclosures of Yoakum, Sartore, Veronese, and Abuchowski (the secondary references) are not relevant to the claims. (App. Br. 14-17.) The secondary references are said to concern purification of linear, not branched polymers, and their purifications are said to involve either unreacted PEG (Yoakum) or PEG conjugates (Sartore, Veronese and Abuchowski). (Id.) Appellants distinguish their own claims as branched, not linear, polymers prior to, not after, conjugation. (Id.) Further, Inventor Harris filed a Declaration said to show by experiment that “the method of Martinez fails to produce a purified polymer 11 Appeal 2009-1274 Application 10/119,546 in any degree.” (Id. at 19-24.) Appellants argue that the Seely8 patent “is instructive in terms of its commentary on the state of the polymer art around the time of the Appellant’s invention,” and supports a conclusion of nonobviousness for Appellants’ claims. (Id. at 25.) Finally, Appellants submitted evidence alleged to show the commercial success of “branched PEGs such as those presently claimed for two currently marketed products.” (Id. at 26.) The issues with respect to this rejection are: Would one of ordinary skill in the art have been motivated to purify Martinez’s polymers? Would one of ordinary skill in the art have combined the PEG linear polymer purification teachings of Sartore, Veronese, Yoakum, and Abuchowski with Martinez’s teaching to purify a PEG branched polymer? Would one of ordinary skill in the art have had an expectation of success applying conventional methods of purifying linear PEG or PEG conjugates to purifying Martinez’s branched polymers free from detectable amounts of unreacted organic reactants and side-products, as well as polymer intermediates and side-products? Does Appellants’ evidence of commercial success weigh in favor of nonobviousness? 8 U.S. Patent No. 5,935,564, which appears to have an effective filing date Mar. 6, 1996, issued to James Ervin Seely, Aug. 10, 1999. 12 Appeal 2009-1274 Application 10/119,546 Principles of Law Relating to Obviousness Obviousness is a question of law based on fact findings. The scope and content of the prior art are determined; differences between the prior art and the claims at issue are ascertained; the level of skill in the art is resolved; and objective record evidence of nonobviousness is considered. Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966). Against that background, the obviousness or nonobviousness of the subject matter is determined. Id.; In re Kahn, 441 F.3d 977, 985 (Fed. Cir. 2006). Where claimed subject matter has been rejected as obvious in view of a combination of prior art references, a proper analysis under § 103 requires, inter alia, consideration of two factors: (1) whether the prior art would have suggested to those of ordinary skill in the art that they should make the claimed composition or device, or carry out the claimed process; and (2) whether the prior art would also have revealed that in so making or carrying out, those of ordinary skill would have a reasonable expectation of success. In re Vaeck, 947 F.2d 488, 493 (Fed. Cir. 1991). “A reference is reasonably pertinent if, even though it may be in a different field from that of the inventor’s endeavor, it is one which, because of the matter with which it deals, logically would have commended itself to an inventor’s attention in considering his problem.” In re Clay, 966 F.2d 656, 659 (Fed. Cir. 1992). A prior art reference is said to teach away from an applicant’s invention “when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). To establish commercial success, 13 Appeal 2009-1274 Application 10/119,546 an applicant must present “hard evidence” that the commercial success is a “direct result of the unique characteristics of the claimed invention – as opposed to other economic and commercial factors unrelated to the quality of the [claimed] subject matter.” In re Huang, 100 F.3d 135, 140 (Fed. Cir. 1996). Analysis of the Obviousness Issue It is undisputed that Martinez taught polymers having the structures Appellants claim. (App. Br. 13.) It is undisputed that Martinez’s unconjugated polymers were not “essentially pure.” It is also undisputed that Martinez taught “the activated branched polymers can be purified by conventional methods” before being conjugated to a biomolecule. (FF8, See App. Br. 13.) Martinez taught the polymers would then be conjugated to proteins or enzymes (FF6), for injection into a patient (FF5). We agree with the Examiner’s finding that the intended in vivo use in a patient would have motivated a person of ordinary skill in the art at the time to purify the polymer before conjugating to a biomolecule. Appellants do not dispute the importance of product purity when in vivo use is intended, but they argue there is nothing in the record to show the art recognized that impurities would arise. (App. Br. 24.) We disagree. The references of record show that the art recognized that PEG chemistry produced impurities, and the references taught removing the impurities. (FF8; FF12; FF15; FF17; FF23.) Appellants stress that the secondary references concern linear PEG, as if branched polymers comprising PEG were exempt from impurities. (Id.) We decline to draw that inference in the 14 Appeal 2009-1274 Application 10/119,546 absence of evidence supporting it. Martinez’s statement to use conventional purification methods (FF8) supports an opposite finding, i.e., that PEG chemistry involves impurities whether the PEG is linear or branched. We note that the structure of Martinez’s “branched” polymers comprises linear PEG moieties linked through a non-PEG linker. We have not been given evidence that those of skill in the art would have thought the PEG used for branched polymer synthesis, or the final product prepared for therapeutic use, was exempt from the toxic contamination Yoakum described (FF18), or that they expected the reactions for branched polymers would be exactly complete leaving no unreacted PEG, unlike the reactions in Veronese (FF15). We find that one of ordinary skill in the art would have been motivated to use conventional purification methods to purify Martinez’s polymers. We turn to the second Vaeck factor, reasonable expectation of success, and to the objective evidence of nonobviousness. Appellants’ arguments fall in three groups: (1) that the secondary references have nothing to do with their own invention; (2) that Martinez and the secondary references did not provide a likelihood of success in achieving essentially pure polymers; and (3) that commercial success weighs in favor of nonobviousness. 1. We find that the secondary references are pertinent to Martinez’s purification disclosure and to Appellants’ claims. A motivated person of ordinary skill in the art, wishing to follow-up on Martinez’s statement that the polymers could be purified by “conventional methods” (FF8), would have looked to the secondary references for conventional purification methods. Martinez reviewed 15 Appeal 2009-1274 Application 10/119,546 conventional PEG conjugation in a “Background” section. (Martinez, col. 1. ll. 5-63.) Martinez contrasted its own branched polymer conjugates with “the string-like structure of conventional polymer conjugates.” (FF7, emphasis added.) We find that when Martinez said the branched polymers can be purified by conventional purification methods, it was referring to the purification methods in use at that time for conventional PEG conjugate molecules. We find that Sartore (FF12), Veronese (FF15) and Abuchowski (FF24, FF25) purified PEG conjugates and that a person of ordinary skill in the art at the time Appellants’ invention was made would have considered them to be in the field of “conventional purification methods” that Martinez named. We agree with Appellants that Yoakum is not in the conjugation field, but we find that Yoakum was reasonably pertinent to the purification problem Martinez addressed. In particular, Yoakum’s PEG reagents were intended for in vivo use, as were Martinez’s PEG polymers. (FF16.) Appellants recognize that Yoakum’s goal was to provide “sterile PEG.” (App. Br. 14.) We find that one of ordinary skill in the art at the time Appellants’ invention was made would have considered Yoakum’s purification method (FF19) reasonably pertinent to the problem of purifying Martinez’s PEG polymers. See Clay, 966 F.2d at 658-59. According to the Specification, Appellants’ “Field of the Invention” “relates to monofunctional derivatives of poly(ethylene glycol) and related polymers and to methods for their synthesis . . . .” (Spec. 1:8-10.) The Field of the Invention is broad. We find linear PEG conjugates are “related polymers.” We reject Appellants’ argument that only branched polymer references are pertinent art, to the exclusion of prior art relating to the “Field 16 Appeal 2009-1274 Application 10/119,546 of the Invention” as the Specification states it. We presume full knowledge by the person of ordinary skill in the art of all the prior art in the field of the inventor’s endeavor. In re Wood, 599 F.2d 1032, 1036 (Fed. Cir. 1979) (citing the specification statement of the field of invention). 2. We find that Martinez and the secondary references provided an expectation of success in achieving essentially pure branched polymers, free from detectable amounts of unreacted organic reactants and side-products, as well as polymer intermediates and side-products. Sartore, Veronese and Yoakum taught that column chromatography removed excess reagents, i.e., unreacted organic reactants, and by-products, i.e., side-products, from an MPEG-protein conjugate. (FF12; FF15; FF19.) Abuchowski taught that dialysis removed unreacted SS-PEG from a PEG- enzyme conjugate. (FF25.) In sum, at the time of Appellants’ invention, conventional methods for purifying PEG-protein conjugates were known. We find that when Martinez said the branched polymer could be purified by conventional methods, Martinez was referring to such conventional polymer purification methods as used by Sartore, Veronese, Yoakum, and Abuchowski. The application of those methods to purifying Martinez’s branched polymers would have been expected to remove detectable amounts of unreacted organic reactants and side-products, as well as polymer intermediates and side-products, because those are the results the secondary references reported when purifying PEG or PEG-protein conjugates. Martinez’s disclosure that the branched polymers could be purified by conventional methods is presumed enabled, and Appellants bear the burden of showing that it is not. See Amgen Inc. v. Hoechst Marion Roussel, Inc., 17 Appeal 2009-1274 Application 10/119,546 314 F.3d 1313, 1355 (Fed. Cir. 2003). We agree with the Examiner that a reasonable expectation of success is bolstered by Martinez’s further teaching of chromatography as a conventional method to purify the conjugate. (Ans. 7; FF9.) Appellants argue that Martinez Examples 1-6, 8 and 9 describe polymers purified by recrystallization, but that Martinez did not confirm purity. (App. Br. 19.) According to Martinez, the “non-limiting examples illustrate certain aspects of the invention.” (Col. 9, ll. 39-40.) None of the examples purport to describe purification. We accept Appellants’ argument that recrystallization was one kind of conventional purification. However, the Examiner’s prima facie case of obviousness is based on evidence from several prior art references that conventional purification methods were not limited to recrystallization and that several forms of column chromatography were conventional. We are not persuaded by the argument that fails to account for the prior art as a whole. Instead, Martinez must be read “for what it fairly teaches in combination with the prior art as a whole.” In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Appellants provide evidence in the Harris Declaration that when Martinez Example 8 was followed, it did not produce the product it should have, U-LYS-PEG. (Decl. ¶ 10.) Declarant reports that when U-LYS-PEG was produced by other means, a recrystallized sample “exhibited a purity that was essentially unchanged from crude mPEG-2-LYS.” (Decl. ¶ 16.) When subjected to gel permeation chromatography, the recrystallized product was shown to have been “contaminated with sizable quantities of the polymeric impurities mPEG, mPEG-1-LYS, and PEG-3.” (Id.) Declarant 18 Appeal 2009-1274 Application 10/119,546 Harris found that “[t]he recrystallization technique of the ‘575 patent does not purify the branched polymer, PEG-2-LYS, to any degree,” (Decl. ¶ 17), and “[t]he recrystallized polymers of the ‘575 patent contain sizable amounts of polymeric impurities” (Decl. ¶ 19.) On the other hand, when crude mPEG-2-LYS was purified by ion exchange chromatography using a DEAE sepharose column as described in co-pending application 10/119,546,9 the purifed product was “essentially absent any detectable polymeric impurities.” (Decl. ¶¶ 14 and 18.) Appellants acknowledge that the Harris Declaration was filed in response to an anticipation rejection based on Martinez alone, not the current obviousness rejection based on combined prior art teachings. (App. Br. 19- 20.) Again, Martinez must be read “for what it fairly teaches in combination with the prior art as a whole.” Merck, 800 F.2d at 1097. Taking into account that the secondary references disclosed conventional methods for purifying PEG polymers, including various forms of chromatography, we do not find the Harris Declaration persuasive of nonobviousness because it does not address the secondary references. According to Appellants, the Seely patent weighs against obviousness because it is instructive on the state of the polymer art around the time of Appellants’ invention. (App. Br. 25.) We find that the passage Appellants selected from Seely simply speaks to the constant need for improving the purity of PEG compounds. Seely is said to “describe[] knowing of no 9 Application 10/119,546 issued to Appellants Sep. 2, 2008, as U.S. Patent No. 7,419,600, with claims to an ion exchange method of purifying a branched polymer. 19 Appeal 2009-1274 Application 10/119,546 preparative chromatographic procedures for successfully separating PEGs.” (Id.) Appellants’ claims are not directed to preparative procedures, and the secondary references taught the preparation of purified PEG-conjugates separated from PEG. Contrary to Appellants’ view that Seely points away from obviousness for their claims (id.), Seely does not “discourage[ ] from following the path set out in [Martinez], or [lead] in a direction divergent from the path that was taken by the applicant.” See Gurley, 27 F.3d at 553. 3. Appellants have not shown that the commercial success of PEGASYS® or MACUGEN® weighs in favor of nonobviousness. Commercial success is a question of fact. Graham, 383 U.S. at 17-18. Appellants argue that if the invention were obvious, “it seems unlikely that Nektar, the assignee of the instant patent application, would be the current manufacturer and supplier of branched PEGs such as those presently claimed for two currently marketed products, Pegasy[s]® and Macugen®, rather than Enzon, the assignee of the Martinez patent.” (App. Br. 26.) The fact that someone is making and selling something, without more, does not support an inference that they should receive a patent. Instead, an applicant must present “hard evidence” that the commercial success is a “direct result of the unique characteristics of the claimed invention – as opposed to other economic and commercial factors unrelated to the quality of the [claimed] subject matter.” Huang, 100 F.3d at 140. We agree with the Examiner that the evidence presented does not meet that test. (Ans. 14- 15.) Appellants argue that their own assignee Nektar, not Enzon, provides the branched PEG for Roche’s PEGASYS® product and Pfizer’s 20 Appeal 2009-1274 Application 10/119,546 MACUGEN® product, the identity of which are said to be shown in Exhibits H and I. (App. Br. 26.) Although not labeled “H” or “I,” we have reviewed the product sheets Appellants attached for PEGASYS®, and MACUGEN®. PEGASYS® is described as pegylated interferon alfa-2a, a PEGylated inteferon. MACUGEN® is described as pegaptanib sodium, a PEGylated oligonucleotide. As we understand the terminology, each product appears to be a conjugate of a therapeutic agent, interferon or oligonucleotide respectively, conjugated to PEG. However, Appellants characterize their own claims as being drawn to unconjugated branched polymers, not to conjugates of polymer with therapeutic agent. Appellants provide no explanation of how commercial success of a conjugated product relates to the unique characteristics of the claimed unconjugated polymers. The proponent of commercial success evidence “must offer proof ‘that the sales were a direct result of the unique characteristics of the claimed invention.’” In re DBC, 545 F.3d 1373, 1384 (Fed. Cir. 2008), quoting Huang, 100 F.3d at 140. The product sheet for PEGASYS® refers to “Nektar’s unique, branched PEG.” However, Appellants admit that Martinez taught the same polymer structures as claimed; accordingly, the claimed structure is not a “unique characteristic” of Appellants’ invention. Exhibits H and I, the product sheets, do not associate Nektar’s branched PEG with the claim phrase “essentially pure.” There is no evidence that commercial success of the Roche and Pfizer products is a “direct result” of the claimed invention. We find the evidence does not meet the required standard, and give it little weight. DBC, 545 F.3d at 1384. 21 Appeal 2009-1274 Application 10/119,546 Appellants provide a printout said to be competitor Enzon’s current webpage, which they refer to as Exhibit E. In the first paragraph under the heading “PEGylation,” the Enzon webpage says “there are five marketed biologic products that utilize our proprietary PEG platform, two of which we market, ADAGEN® and ONCASPAR®, and three for which we receive royalties, PEG-INTRON®, PEGASYS®, and MACUGEN®.” Thus, Appellants’ evidence shows that Enzon, the assignee of the Martinez patent, is receiving royalties for the Roche and Pfizer products that Appellants’ assignee Nektar provides PEG for. It is undisputed that the Martinez patent disclosed the structures now claimed, although the purity is disputed. Where royalties are being paid to the assignee of the Martinez patent, it is unclear that commercial success inures to Appellants’ invention or to licensing arrangements. This is not the “hard evidence” required under Huang that commercial success is due to the unique characteristics of Appellants’ invention. See DBC, 545 F.3d at 1384 (commercial success potentially attributable to marketing factors rather than the characteristics of the invention receives little weight). Appellants refer to Exhibits F and G, said to describe Nektar’s partnerships with each of Roche and Pfizer. Although listed as attachments, we do not find these two exhibits in the record. CONCLUSIONS OF LAW We conclude that a person of ordinary skill in the art of water soluble polymers could determine if a particular composition is an “essentially pure” polymer; 22 Appeal 2009-1274 Application 10/119,546 We find that one of ordinary skill in the art have been motivated to purify Martinez’s polymers; We find that one of ordinary skill in the art would have combined the teachings of Sartore, Veronese, Yoakum, and Abuchowski with Martinez’s teachings; We find that one of ordinary skill in the art would have had an expectation of success in using conventional purification methods to purify Martinez’s polymers free from detectable amounts of unreacted organic reactants and side-products, as well as polymer intermediates and side- products; We find that Appellants did not provide hard evidence showing commercial success; and We conclude that Martinez, Yoakum, Sartore, Veronese, and Abuchowski rendered obvious Appellants’ branched polymers free from detectable amounts of unreacted organic reactants and side-products, as well as polymer intermediates and side-products. SUMMARY We reverse the rejection of claims 96-109, 111, 112, 114-124, and 133 under 35 U.S.C. § 112, ¶ 2, as indefinite; and We affirm the rejection of claims 96-109, 111, 112, 114-124, and 133 under 35 U.S.C. § 103(a) as obvious over the combined teachings of Martinez, Sartore, Veronese, Yoakum, and Abuchowski. 23 Appeal 2009-1274 Application 10/119,546 No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED cdc NEKTAR THERAPEUTICS 201 INDUSTRIAL ROAD SAN CARLOS CA 94070 24 Copy with citationCopy as parenthetical citation