Ex Parte Ballance et alDownload PDFPatent Trial and Appeal BoardMay 12, 201711927600 (P.T.A.B. May. 12, 2017) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/927,600 10/29/2007 David J. Ballance 09531.0003-04000 6216 22852 7590 05/16/2017 FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER LLP 901 NEW YORK AVENUE, NW WASHINGTON, DC 20001-4413 EXAMINER ROBINSON, HOPE A ART UNIT PAPER NUMBER 1652 NOTIFICATION DATE DELIVERY MODE 05/16/2017 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): regional-desk @ finnegan. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte DAVID J. BALLANCE, DARRELL SLEEP, CHRISTOPHER P. PRIOR, HOMAYOUN SADEGHI, and ANDREW J. TURNER1 Appeal 2016-003160 Application 11/927,600 Technology Center 1600 Before JEFFREY N. FREDMAN, TIMOTHY G. MAJORS, and DEVON ZASTROW NEWMAN, Administrative Patent Judges. MAJORS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to albumin fusion proteins comprising a Factor VII polypeptide, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 Appellants identify the Real Party in Interest as NOVOZYMES BIOPHARMA DK A/S. (App. Br. 3.) Appeal 2016-003160 Application 11/927,600 STATEMENT OF THE CASE Appellants’ “invention relates generally to Therapeutic proteins (including, but not limited to, a polypeptide, antibody, or peptide, or fragments and variants thereof) fused to albumin or fragments or variants of albumin.” (Spec. 1:12—14.) According to the Specification, such fusion proteins “exhibit extended shelf-life and/or extended or therapeutic activity in solution.” (Id. at 1:16—17.) Claims 61, 63, 67—77, 81, 93, and 98—1072 are on appeal. Claim 61 is the only independent claim and reads as follows: 61. An albumin fusion protein comprising a Factor Vll polypeptide fused to an albumin polypeptide, wherein said albumin polypeptide has the ability to prolong the serum half-life of the fused Factor Vll polypeptide compared to the unfused Factor Vll polypeptide, wherein said fused Factor VII polypeptide has Factor VII coagulant activity, wherein said Factor VII polypeptide is fused at the N-terminus of the albumin polypeptide, and wherein the albumin polypeptide is selected from: a) a full-length albumin; b) a mature albumin; c) a fragment of albumin; and d) a polypeptide consisting of an amino acid sequence at least 95% identical to SEQ ID NO: 18; and wherein the Factor VII polypeptide is selected from: i) a full-length Factor VII; ii) an activated Factor VII (Factor Vila); iii) a fragment of a Factor VII having a deletion that consists of 1-50 amino acid residues as compared to mature Factor VII; 2 The Examiner asserts that claims 61—63, 67—77, 81, 82, and 93—107 stand rejected. (Ans. 3.) Claims 62, 82, and 94—97 are, however, canceled. (See Non-Final Rejection, mailed May 27, 2015 (“Non-Final Act.”), 2). 2 Appeal 2016-003160 Application 11/927,600 iv) a polypeptide consisting of an amino acid sequence at least 90% identical to amino acids 39 to 444 of SEQ ID NO: 47; and v) a mature Factor VII. (App. Br. (Claims App’x 1).) The claims stand rejected under 35 U.S.C. § 103(a) over Ballance3 and Fleer.4 (Ans. 3.) Appellants identify the following pending appeals as related: 1) U.S. Application No. 13/855,434 (Appeal No. 2016-003294); 2) U.S. Application No. 13/855,454 (Appeal No. 2016-003295); and 3) U.S. Application No. 11/927,602 (Appeal No. 2016-005026). (See App. Br. 3.) DISCUSSION Issue The Examiner rejected claims 61, 63, 67—77, 81, 93, and 98—107 as obvious over Ballance and Fleer. (Ans. 3.) The Examiner finds that “Ballance et al. teaches fusion proteins comprising human serum albumin (protein of 585 amino acids) and human growth hormone . . . [and] that the albumin fusion protein extends the half-life in the circulation of the fusion partner protein compared to an unfused state.” (Id. ) According to the Examiner, Ballance also teaches “the fusion protein comprises a fragment that may be the N-terminal portion or C-terminal portion.” (Id.) 3 Ballance, WO 97/24445, published July 10, 1997. 4 Fleer et al., US 5,876,969, issued Mar. 2, 1999. 3 Appeal 2016-003160 Application 11/927,600 The Examiner finds that Ballance “does not expressly teach the stabilization of Factor VII (i.e. prolonging the half-life),” and thus turns to Fleer. (Id. at 4.) According to the Examiner, “Fleer teach[es] albumin fusion proteins with a number of therapeutic proteins and state [s] that albumin can be fused to coagulation factors ... for the purposes of prolonging the half-life.” (Id.) Fleer, the Examiner finds, “is not limited to a single coagulation factor, thus the claimed FVII fragment, full-length or FVIIa is included.” (Id.) The Examiner concludes the claimed fusion protein would have been obvious. (Id. at 4—5.) The Examiner reasons the skilled artisan “would be motivated to modify the conjugate taught by Ballance et al. by replacing the growth hormone with Factor VII. . . based on the disclosure of Ballance et al. of the function of albumin as prolonging the half-life of other proteins in circulation.” (Id. at 5.) Further, the Examiner reasons, the skilled person “would [] have a reasonable expectation of success . . . because Fleer et al. teach that albumin can be fused to coagulation factors and Factor VII is one such factor, and [Fleer] exemplify at least one coagulation factor [von Willebrand factor or vWF] fused to albumin.” (Id.) Appellants argue the combination of Ballance and Fleer fails to render the claims obvious. Appellants contend Fleer’s disclosure of “a genus of albumin fusion proteins containing a coagulation factor does not render obvious the claimed species of a Factor VH-albumin fusion protein.” (App. Br. 6—8.) Appellants further contend that, at the time of the invention, the skilled artisan “would not have predicted that albumin fusion would ‘prolong the serum half-life of the fused Factor VII polypeptide’ as 4 Appeal 2016-003160 Application 11/927,600 claimed.” (Id. at 6, 9—19.) Appellants argue the skilled person “would not have predicted the orientation-dependent coagulant activity of the claimed Factor VH-albumin fusion proteins” and more specifically “Appellants’] unexpected discovery that Factor VII retains biological activity only when fused to the amino-terminal [N-terminal] end of albumin.” (Id. at 6, 19—29.) Appellants further argue “there had been a long-felt need in the art for a therapeutic Factor VII having an extended half-life” that “the claimed invention satisfies,” and that “others . . . had tried and failed to develop an extended half-life Factor VII protein.” (Id. at 30-33.) In support of its arguments concerning the patentability of the claims on appeal, Appellants cite to, among other things, several declarations from skilled persons and publications in the scientific literature. We discuss Appellants’ evidence further below. (App. Br. passim.) The issue on appeal is whether the preponderance of the evidence of record supports the Examiner’s conclusion of obviousness. Findings of Fact (FF) The Examiner’s findings of fact and statement of the rejection are provided at pages 3—6 of the Examiner’s Answer and pages 7—11 of the May 27, 2015 Non-Final Rejection. (See also Ans. 11—33 (Response to Argument); Non-Final Act. 12—14 (Response to Arguments).) FF 1. Ballance teaches “fusion of a molecule of albumin, or variants or fragments thereof, to a molecule of growth hormone or variants or fragments thereof, the fusion proteins having an increased circulatory half- life over unfused growth hormone.” (Ballance 3:27—30.) 5 Appeal 2016-003160 Application 11/927,600 FF 2. Ballance teaches: Preferably, the fusion protein comprises HA [human albumin], or a variant or fragment thereof, as the N-terminal portion, with hGH [human growth hormone] or a variant or fragment thereof as the C-terminal portion [i.e., hGH is fused to the C-terminal end of the albumin], so as to minimise any possible negative effects on receptor binding. Alternatively, a fusion protein comprising HA, or a variant or fragment thereof, as the C- terminal portion, with hGH or a variant or fragment thereof as the N-terminal portion, may also be capable of signal transduction. Generally, the polypeptide has only one HA- derived region and one GH-derived region. {Id. at 4:3-11.) FF 3. Fleer teaches “[biologically active polypeptides comprising a therapeutically active polypeptide fused to human serum albumin or a natural variant thereof.” (Fleer Abstract.) Fleer further teaches “albumin variants designate any protein with a high plasma half-life which is obtained by modification.” {Id. at 1:23—25.) FF 4. Fleer teaches the polypeptide having a therapeutic activity is a polypeptide of human origin or a molecular variant. For example, this may be all or part of an enzyme, an enzyme inhibitor, an antigen, an antibody, a hormone, a factor involved in the control of coagulation, an interferon, a cytokine ... of a growth factor and/or of differentiation [and for example the transformant growth factors (TGFs), the blood cell differentiation factors (erythropoietin, M-CSF, G-CSF, GM-CSF and the like), insulin and the growth factors resembling it (IGFs), or alternatively cell permeability factors (VPF/VEGF), and the like] ... of a cytostatic factor (and for example the proteins which bind to galactosides), of a plasma (and for example von Willebrand factor, fibrinogen and the like).... {Id. at 2:22-49 (brackets in original) (emphases added).) 6 Appeal 2016-003160 Application 11/927,600 FF 5. Fleer teaches The active part of the molecules of the invention can be coupled either directly or via an artificial peptide to albumin. Furthermore, it may constitute the N-terminal end as well as the C-terminal end of the molecule. Preferably, in molecules of the invention, the active part constitutes the C-terminal part of the chimera [i.e., polypeptide fused to C-terminal of albumin], {Id. at 3:28-33.) Principles of Law “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSRIntI Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Prima facie obviousness may be rebutted with evidence of secondary considerations and when such evidence is submitted, all of the evidence is considered anew. In re Piasecki, 745 F.2d 1468, 1472—73 (Fed. Cir. 1984). Secondary considerations include, inter alia, long-felt but unsolved needs, failure of others, and unexpected results. In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998). Analysis Claim 61 Looking to the Examiner’s findings and reasoning concerning the combination of Ballance and Fleer alone, we agree that claim 61 would have been prima facie obvious.5 But considering the totality of the evidence of 5 The Examiner finds “there is a need in the art to improve bleeding episode therapies, the advantage of cost savings and increased in vivo circulating life of Factor VII” and “FVII was being used as a medicament and was known to 7 Appeal 2016-003160 Application 11/927,600 record, we reach a different conclusion. Neither Ballance nor Fleer disclose fusions with Factor VII and, although Fleer briefly mentions factors involved in coagulation, coagulation factors encompass dozens of potential polypeptides. (App. Br. 7.) Also, the functionally closest peptide tested in Fleer, von Willebrand factor, which can reasonably be characterized as a coagulation factor, did not exhibit coagulant activity as required by the claims. (Id. at 8—9.) As we discuss in greater detail below, Appellants have provided persuasive and countervailing objective evidence of nonobviousness. When this evidence is considered along with the teachings of Ballance and Fleer, the decision tilts in Appellants’ favor. Appellants emphasize that, in mentioning “a factor involved in the control of coagulation,” Fleer discloses a broad genus that “may comprise many functionally and structurally distinct polypeptides.” (App. Br. 6—7 (citing Tanaka* * * * 6).) Appellants also point out that, in the lone example in which Fleer tested fusion proteins comprising a coagulation factor — fragments of vWF — that these fusion constructs “inhibit the physiological function of vWF, not [] enhance its normal coagulant activity as contemplated by the instant invention.” (Id. at 9.) The fact that coagulation factors have diverse structures and functions does not, in itself, persuade us that the Examiner’s reliance on Fleer is have a short half-life.” (Ans. 5 and 28.) Although the Examiner cites to no prior art support for these findings, showing the same to have been known by skilled artisans at the time of the invention, Appellants do not appear to dispute the Examiner on these points. 6 Tanaka et al., Blood Coagulation: Hemostasis and Thrombin Regulation, 108:5 Anesthesia & Analgesia 1433^46 (2009). 8 Appeal 2016-003160 Application 11/927,600 flawed. To the contrary, as the Examiner noted, “Fleer provides a myriad of therapeutic proteins as potential fusion partners which demonstrates that different protein structures with different functions can be fused to albumin.” (Ans. 13—14.) Put differently, in expressly reciting polypeptides with quite different structures and functions (e.g., EPO versus vWF), Fleer suggests the design of active therapeutic fusion constructs despite the diversity. That said, Appellants’ contention that the vWF-fusion constructs exemplified in Fleer inhibit coagulant activity — opposite from vWF’s normal activity and what is claimed — weakens somewhat the notion that an ordinarily skilled person would have a reasonable expectation of success in designing a Factor VII fusion protein with coagulant activity as claimed. (App. Br. 8—9.) Appellants argue Ballance and Fleer must be viewed through the lens of “background knowledge in the art.” (App. Br. 11.) This knowledge, Appellants contend, is that “the circulatory half-life of a polypeptide depended on its molecular size due to much faster renal clearance of small polypeptides from the blood plasma.” {Id. at 9.) According to Appellants’ declarant, Dr. Sleep,7 it was known in the art that “plasma clearance of proteins decreased rapidly with increasing molecular size from about 20 kD to about 60-70 kD . . . [and] a size of 60-70 kD or above showed only very little or almost no renal clearance.” (Sleep Decl. 14.) It “was also known in the art that the serum half-life of a small protein, such as human growth hormone (hGH), could be increased by expressing it as a genetic fusion with 7 Declaration of Dr. Darrell Sleep Under 37 C.F.R. § 1.132 dated March 24, 2014 (“Sleep Decl.”) Dr. Sleep cites a number of publications in support of his opinions. We omit citation to most of those references here for brevity. 9 Appeal 2016-003160 Application 11/927,600 human serum albumin (HSA), which is a large (67 kD) protein.” (Id. at | 5.) Dr. Sleep declares that “at the priority date of [the present application] it was thought in the art that FVII and FVIIa were too large for clearance from circulation via the kidneys. . . . Thomsen [for example] taught that ‘the 50 kDa glycoprotein FVIIa molecule is a low clearance compound.’” (Id. at 17.)8 Thus, Dr. Sleep opines, “one skilled in the art would have thought that Factor VII and Factor Vila are already large enough to be excluded from renal secretion, and therefore would not have expected that fusing Factor VII or Factor Vila to albumin would prolong the circulatory half-lives of these factors to any useful extent.” (Id.) When viewed in this historical context, Appellants contend, this explains why the working examples in Ballance and Fleer fused albumin to smaller polypeptides or fragments, with the largest having a molecular weight of about 27 kD. (App. Br. 14.) According to Appellants, “nothing in Ballance and Fleer provided any reasonable expectation that albumin fusion would increase the half-life of substantially larger polypeptides, such as Factor VII.” (Id. at 15.) Here again, this evidence and argument alone from Appellants does not persuade us the Examiner erred in concluding that claim 61 would have been obvious. Fleer teaches that “albumin variants designate any protein with a high plasma half-life which is obtained by modification” (FF 3) and, in expressly teaching the fused polypeptide may be “all or part of an enzyme 8 See Thomsen et al., Pharmacokinetics of Recombinant Factor Vila in the Rate A Comparison of Bio-, Immuno- and Isotope Assays, 70:3 Thrombosis and Haemostasis 458-64 (1993). 10 Appeal 2016-003160 Application 11/927,600 [etc.],” Fleer suggests its constructs are not limited to fusions with fragments or small molecules. (FF 4.) Also, as the Examiner notes, Fleer identifies a number of polypeptides that have somewhat larger molecular weights (e.g., EPO). (Ans. 12—13.) Moreover, while FVII polypeptides may have been recognized as a low clearance compound based on size (approx. 50 kD), the size is still below the renal permeability threshold (60—70 kD) reported in the art and Dr. Sleep’s declaration. (See, e.g., Sleep Deck 4, 7.) Accordingly, by fusing to albumin, some increase in circulatory half-life — even if minor — would have reasonably been expected. Nevertheless, the Appellants’ evidence does at least suggest the skilled person at the time of the invention would not have expected that fusing FVII to albumin would have necessarily resulted in a substantial increase in half-life. Appellants next cite to data concerning orientation dependency and unexpected results when Factor VII is fused to the N-terminal end of albumin. (App. Br. 20—23.) According to Appellants, testing provided by Dr. Thomas Weimer9 shows the criticality of FVII fusions at the N-terminus: “the activity-to-antigen ratio of the N-terminal fusion protein (protein 937) is at least about 20-fold larger than that of the C-terminal fusion protein (protein 2396.)” (Id. at 21 (citing Weimer 2012 Deck 1 6).) In contrast, “the activity-to-antigen ratio approaches zero for the fusion protein with Factor VII fused [only] at the C-terminal end of albumin.” (Id.) Also citing Dr. 9 Dr. Weimer submitted two declarations. (See Declaration of Dr. Thomas Weimer Under 37 C.F.R. § 1.132 dated April 25, 2012 (“Weimer 2012 Deck”); see also Declaration of Dr. Thomas Weimer Under 37 C.F.R. § 1.132 dated Sept. 3, 2013 (“Weimer 2013 Deck”).) 11 Appeal 2016-003160 Application 11/927,600 Weimer’s testing, Appellants point out that double fusions (fusing FVII to both the C- and N-terminal ends of albumin) provide a protein with significant activity compared to fusion constructs at the C-terminal end only, “which is virtually inactive.” (Id. at 22 (citing Weimer 2013 Decl. 7.) According to Appellants (and Dr. Weimer), “both Ballance and Fleer teach that therapeutic polypeptides are preferably fused at the C-terminal end of albumin, which is opposite to the orientation recited in the claims on appeal.” (Id. at 23; see also Weimer 2013 Decl. 112.) Appellants’ data concerning the claimed N-terminal fusions provides persuasive objective evidence of nonobviousness. The Examiner’s response relies heavily on the prima facie case, and the teachings in both Ballance and Fleer that polypeptides may be fused to the N- or C- terminal end of albumin. (Ans. 23—26.) The Examiner has not, however, provided persuasive evidence or scientific reasoning explaining why the results Appellants produced would have been expected.10 Indeed, as Appellants contend, the prior art suggests the opposite — that optimal activity would have been observed when a polypeptide is fused at the C-terminal end of albumin. (Reply Br. 13—14; FF 2, 5.) Although we do not limit the prior art to its preferred embodiments, here the evidence unexpectedly shows that, had the skilled artisan modified Ballance and Fleer to include FVII fused to the C-terminus, the result would have been a virtually inactive protein. 10 The Examiner asserts that Drs. Weimer and Sleep appear to contradict each other (Ans. 20), and that Appellants have provided “contradictory statements” (id. at 24). For the reasons given by Appellants, we are unpersuaded there is any discrepancy. (Reply Br. 11—12.) 12 Appeal 2016-003160 Application 11/927,600 We recognize, but are not persuaded by, the Examiner’s emphasis in the Response to Argument, that Fleer claims a double-fusion construct. (Ans. 21—26.) On the record here, the mention of double fusions in Fleer’s claims is not entitled to any talismanic importance without an accompanying disclosure teaching or suggesting a particular advantage of such a construct. Fleer, as does Ballance, clearly prefers fusions at the C-terminal end of the albumin, and suggests those fusion proteins provide optimal therapeutic activity. (FF 2, 5.) The Examiner, however, asserts that the skilled person “could conclude that because Fleer claims a double fusion in claim 1 after making single fusions at both terminus that they were aware that the double fusion produced the highest activity.” (Ans. 21.) This is speculation. And, in any event, when obviousness is at issue the question is not what the skilled person could have concluded or done, but what they reasonably would have done. See Belden Inc. v. Berk-TekLLC, 805 F.3d 1064, 1073 (Fed. Cir. 2015). The Examiner also responds that “there is a high expectation of success, because Ballance and Fleer made albumin fusion proteins comprising therapeutic proteins that are C-terminally or N-terminally oriented and Fleer also made a fusion that was N and C terminally oriented.” (Ans. 23.) We are not persuaded. Fusions with Factor VII having any of these orientations were not made. And, as noted by Appellants and Dr. Weimer, neither Ballance nor Fleer discloses any in vivo therapeutic activity when a polypeptide is fused to the N-terminal end of albumin, while such activity is disclosed for C-terminal fusions. (See Weimer 2013 Decl. Tflf 13— 13 Appeal 2016-003160 Application 11/927,600 14.)11 Inasmuch as the Examiner invokes an inherency rationale (Ans. 23, 27) to produce a FVII polypeptide with the claimed “coagulant activity” when fused at the N-terminal, we are unpersuaded. See Par Pharma., Inc. v. Twi Pharms., Inc., 773 F.3d 1186, 1195—96 (Fed. Cir. 2014) (holding that a “high standard” must be met “to rely on inherency to establish the existence of a claim limitation in the prior art in an obviousness analysis.”) This is especially so when the “natural result” of the combination of Ballance and Fleer would have been a fusion at the C-terminal end of albumin, yet Appellants’ data shows the FVII polypeptide is unexpectedly inactive unless there is also a fusion at the N-terminus. Id. at 1196. Appellants contend the claimed invention satisfies a long-felt need to produce extended half-life FVII therapeutics, and that other “major players in the field” have tried and failed to develop such therapeutics. (App. Br. 30—33.) In support, Appellants cite the declaration of Dr. Veldman.12 Dr. Veldman declares “there are no extended half-life FVII constructs approved for use in the United States.” (Veldman Decl. 13.) Dr. Veldman identifies efforts by Novo Nordisk and Bayer Healthcare to develop an extended half- life FVII, but states that these efforts were unsuccessful as evidenced by the termination of phase II/III studies of Novo Nordisk’s and Bayer’s respective 11 Ballance discloses that in vitro testing showed that fusions of hGH to the N-terminal end of albumin were “significantly less potent” than fusions at the C-terminal end. (See Ballance 22:4—7; see also Weimer 2013 Decl. 114.) 12 See Declaration of Dr. Alex Veldman Under 37 C.F.R. § 1.132 dated Mar. 21, 2014 (“Veldman Decl.”). The Veldman Decl. cites to various other documents, including press releases, financial reports, and clinical trials. We do not cite each of these documents here for brevity. 14 Appeal 2016-003160 Application 11/927,600 constructs due to problems encountered during testing. (Id. at || 3 4.) In contrast, Dr. Veldman states that “CSL Behring recently completed a phase I clinical study . . . demonstrating the safety and prolonged half-life of a Factor VH-albumin construct encompassed by the claims . . . [and] CSL Behring has sought regulatory approval to move forward with a phase II/III trial.” (Id. at 14.) Dr. Veldman thus opines “the claimed FVII-albumin construct may satisfy a long-felt medical need for FVII constructs exhibiting extended half-life in an area where others in the field have not met with success.” (Mat | 5.) In response, the Examiner again relies principally on the prima facie case. (Ans. 27—28.) According to the Examiner, “[t]he need in the art was addressed by the cited references .... The sole purpose of the fusions made by Ballance and Fleer was to extend, Fleer made a fusion with a coagulation factor (vWF) and suggest that other[s] can be made as well.” (Id.) Appellants’ evidence of an alleged long-felt need that is met by the claimed fusion protein is not strong. Appellants did not persuasively show a persistent need recognized by skilled persons. See In re Gershon, 372 F.2d 535, 538 (CCPA 1967). For example, Appellants and Dr. Veldman provide no clear timetable showing when the need for extended half-life FVII therapeutics was first recognized by skilled persons and its persistence over the years. The evidence cited by Appellants and Dr. Veldman appears to reflect work in much more recent times (e.g., 2011, 2013), well after the putative priority date of the present invention. (Veldman Deck 3M.) Even assuming a long-felt need existed at the time of the application, Appellants also do not persuasively show that the FVII-albumin construct 15 Appeal 2016-003160 Application 11/927,600 that is being tested by CSL Behring satisfies the need. See In re Cavanagh, 436 F.2d 491, 496 (CCPA 1971). Dr. Veldman’s opinion that this construct “may satisfy” the need is, at best, equivocal. (Veldman Decl. 1 5.) And, while phase I testing of the construct shows promise, there is no guarantee that problems will not arise in phase II/III (as they did for Novo Nordisk and Bayer). (Id. at 13.) We do, however, attribute weight to Appellants’ evidence showing an apparent failure by others to develop extended half-life FVII therapeutics. “The purpose of evidence of failure of others is to show indirectly the presence of a significant defect in the prior art, while serving as a simulated laboratory test of the obviousness of the solution to a skilled artisan.” In re Cyclobenzaprine Hydrocholoride Extended-Release Capsule Patent Litig., 676 F.3d 1063, 1082 (Fed. Cir. 2012) (citations and internal quotation marks omitted). The record indicates that Novo Nordisk and Bayer were unable to successfully develop effective extended half-life FVII constructs. (Veldman Decl. 13.) The record also indicates that Novo Nordisk’s and Bayer’s constructs did not comprise a FVII-albumin fusion protein. (Id.) See In re Cyclobenzaprine, 676 F.3d at 1082 (“Evidence that others were going in different ways is strong evidence that the [inventor’s] way would not have been obvious.”) (citation and internal quotation marks omitted). When the Examiner’sprima facie case is considered anew, in light of all the evidence of record, we are unpersuaded that claim 61 would have been obvious over Ballance and Fleer. Appellants have provided persuasive argument and objective evidence of nonobviousness that rebuts the Examiner’s evidence of obviousness. Mintz v. Dietz & Watson, Inc., 679 16 Appeal 2016-003160 Application 11/927,600 F.3d 1372, 1379 (Fed. Cir. 2012) (“Obviousness requires . . . walking] a tightrope blindfolded (to avoid hindsight)—an enterprise best pursued with the safety net of objective evidence.”) This is not a case where the prima facie case is so strong that it controls the obviousness determination. See Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372 (Fed. Cir. 2007). We thus reverse the rejection of claim 61 and its dependent claims. We decline to address Appellants’ separate argument and evidence concerning the patentability of claims 81, 99, 102, 103, 106, and 107, as each of those claims depends from claim 61. In re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992) (“[Dependent claims are nonobvious if the independent claims from which they depend are nonobvious.”) Conclusion of Law We conclude the preponderance of the evidence of record does not support the Examiner’s conclusion that claims 61, 63, 67—77, 81, 93, and 98—107 would have been obvious over Ballance and Fleer. SUMMARY We reverse the rejection of claims 61, 63, 67—77, 81, 93, and 98—107 under 35 U.S.C. § 103(a) over Ballance and Fleer. REVERSED 17 Copy with citationCopy as parenthetical citation