Gregory Bleck et al.Download PDFPatent Trials and Appeals BoardMay 4, 20212019006293 (P.T.A.B. May. 4, 2021) 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. 13/419,045 03/13/2012 Gregory Thomas Bleck GALA-31720.202 6788 145292 7590 05/04/2021 Casimir Jones, S.C. 2275 Deming Way, Suite 310 Middleton, WI 53562 EXAMINER HOLLAND, PAUL J ART UNIT PAPER NUMBER 1656 NOTIFICATION DATE DELIVERY MODE 05/04/2021 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): docketing@casimirjones.com pto.correspondence@casimirjones.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ________________ Ex parte GREGORY THOMAS BLECK, IAN JOHN COLLINS, and MARK JOSEPH FREY1 ________________ Appeal 2019-006293 Application 13/419,045 Technology Center 1600 ________________ Before JOHN G. NEW, TAWEN CHANG, and RACHEL H. TOWNSEND, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL 1 We use the term “Appellant” to refer to the “applicant” as defined in 37 C.F.R. § 1.142. Appellant identifies Catalent Pharma Solutions, LLC as the real party-in-interest. App. Br. 3. Appeal 2019-006293 Application 13/419,045 2 SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner’s Non-Final Rejection of claims 10–12 and 17–25. Specifically, claim 10 stands rejected as unpatentable under 35 U.S.C. § 103 as being obvious over the combination of Ruoslahti et al. (US 6,277,812 B1, August 21, 2001) (“Ruoslahti I”), Meade et al. (US 2005/0160483 A1, July 21, 2005) (“Meade”), Do et al. (WO 03/089636 A1, October 30, 2003) (“Do”), Z. von Marschall et al., Decorin is Processed by Three Isoforms of Bone Morphogenetic Protein-1 (BMP1), 391 BIOCHEM. AND BIOPHYS. RES. COMMS. 1374–78 (2010) (“von Marschall”) and Bremel et al. (US 6,852,510 B2, February 8, 2005) (“Bremel”). Claims 11, 12, 19, and 25 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over Ruoslahti I, Meade, Do, von Marschall, Bremel, and Pang (US 2003/0124152 A1, July 3, 2003) (“Pang”). Claims 17, 18, 20, and 21 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over Ruoslahti I, Meade, Pang, Do, von Marschall, Bremel, and Ohigashi (US 2010/0145020 A1, June 10, 2010) (“Ohigashi”).2 Claims 22–24 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over Ruoslahti I, Meade, Pang, Do, von Marschall, Bremel, 2 The Examiner also cites to Ohigashi (WO 2008/117735 A1, October 2, 2008) (in Japanese). Appeal 2019-006293 Application 13/419,045 3 Ohigashi, and Hasslacher et al. (WO 2011/012726 A2, February 3, 2011) (“Hasslacher”). We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. NATURE OF THE CLAIMED INVENTION Appellant’s claimed invention is directed to improved decorin compositions and methods of their production. Spec. Abstr. REPRESENTATIVE CLAIM Independent claim 10 is representative of the claims on appeal, and recites: 10. A host cell comprising a retroviral vector comprising a nucleic acid sequence encoding a fusion protein comprising an alpha-lactalbumin signal sequence operably linked to a sequence encoding a decorin core protein, wherein said fusion protein comprises the amino acid sequence of SEQ ID NO:4, said host cell is a Chinese Hamster Ovary (CHO) cell, and said host cell secretes non-gagylated mature decorin core protein at a rate of greater than 10 picograms/cell/day when cultured. App. Br. 13. ISSUES AND ANALYSES We adopt the Examiner’s findings, reasoning, and conclusion that the claims on appeal are prima facie obvious over the combined cited prior art. We address the arguments raised by Appellant below. Appeal 2019-006293 Application 13/419,045 4 Issue Appellant argues that the Examiner erred because nothing in the prior art would have led a person of ordinary skill in the art to identify Ruoslahti I as the lead prior art or motivated such person to make the specific modification to Ruoslahti I (viz., use of retroviral vectors and the claimed signal sequence in the Ruoslahti I process), as concluded by the Examiner. App. Br. 7. Analysis The Examiner finds that Ruoslahti I teaches a vector comprising a nucleic acid encoding a fusion protein comprising a maltose binding protein operably linked to a decorin core protein, in which the decorin core protein comprises a mutation at the serine in position 4, which is changed to coding for threonine or alanine. Non-Final Act. 4 (see Ruoslahti I col. 3, ll. 37–41). The Examiner notes that the mutation of serine at position 4 to alanine would cause the decorin core protein of Ruoslahti I to share 100% identity with full-length human decorin, and 95.6% identity to the amino acid sequence of SEQ ID NO: 4. Id. The Examiner finds that the mutation at serine 4 to alanine would result in a non-gagylated decorin protein. Id. (citing Ruoslahti I col. 3, ll. 10–23, col. 10, ll. 40–52; see also Non-Final Act. App’x A, B). The Examiner further finds that Ruoslahti I teaches that the decorin can be rendered glycosylaminoglycan-free by, inter alia, mutation. Non- Final Act. 4 (citing Ruoslahti I col. 7, ll. 64–67). The Examiner finds that Ruoslahti I also teaches host cells, e.g., Chinese Hamster Ovary (“CHO”) Appeal 2019-006293 Application 13/419,045 5 and COS-1 cells, comprising the vector. Id. at 5 (citing Ruoslahti I col. 10, ll. 59–67, col. 11, ll. 18–20). However, the Examiner finds that Ruoslahti I does not teach that the vector of claim 10 is a retroviral vector encoding an alpha-lactalbumin signal sequence operably linked to a [sequence encoding a] decorin core protein, in which the fusion protein comprises the amino acid sequence of SEQ ID NO:4, and in which the host cell secretes non-gagylated mature decorin protein at a rate of greater than 10 picograms/cell/day when cultured. Non- Final Act. 5. The Examiner finds that Meade teaches a vector comprising a nucleic acid including a decorin protein-coding sequence operatively linked to a tissue specific promoter, such as an alpha-lactalbumin signal sequence, which directs the expression of decorin and that results in the secretion of the protein. Non-Final Act. 5 (citing Meade ¶¶ 23, 31, 128, 161–163). The Examiner finds that Do teaches fusion proteins combining alpha- lactalbumin with glycoproteins for transfection and recombinant expression of the proteins in cells. Non-Final Act. 5 (citing Do Abstr., 1). The Examiner finds that Do also teaches an alpha-lactalbumin signal peptide sequence that is 100% identical to the alpha-lactalbumin signal sequence of SEQ ID NO: 4. Id. (see also Non-Final Act. App’x C). The Examiner finds that von Marschall teaches that the amino- terminus of decorin and the propeptide begins with GPFQQ by processing of the leader sequence and teach the leader sequence, propeptide, and mature peptide of human decorin. Non-Final Act. 5 (citing von Marschall 1376). Appeal 2019-006293 Application 13/419,045 6 The Examiner also points to Figure 18 of von Marschall, which is reproduced below. Figure 18 of von Marschall depicts the notation of the leader, propeptide, and first several amino acids of the human preprodecorin sequence The Examiner finds that Bremel teaches the production of proteins in host cells, such as CHO cells, containing multiple integrated copies of a retroviral integrating vector useful for the production of pharmaceutical proteins at high levels. Non-Final Act. 6. The Examiner finds that Bremel teaches that the integrating vectors contain at least one exogenous gene operably linked to a promoter, and that, in some embodiments, the promoter is an alpha-lactalbumin promoter and a secretion signal that facilitate secretion of the protein when cultured, whereby the host cells synthesize a protein greater than about 10 picograms/cell/day of the protein of interest. Id. (citing Bremel Abstr., col. 2, ll. 19–35, cols. 2–3, ll. 61–25, cols. 4–5, ll. 61–6). The Examiner concludes that it would have been obvious to a person of ordinary skill in the art to combine the teachings of Ruoslahti I, Meade, Do, von Marschall, and Bremel to design a retroviral vector encoding a construct having the amino acid sequence of SEQ ID NO: 4 for expression in a CHO host cell. Non-Final Act. 6. The Examiner notes that both Ruoslahti I and Meade teach fusion proteins of decorin having an alpha- lactalbumin signal sequence and production in a CHO cell. Id. The Appeal 2019-006293 Application 13/419,045 7 Examiner further notes that Do teaches alpha lactalbumin fusion to glycoproteins aids in protein expression, and that von Marschall teaches the leader sequence and propeptide of human decorin. Id. The Examiner further cites Bremel as teaching that production of proteins in host cells, such as CHO cells containing multiple integrated copies of a retroviral integrating vector, are useful for the production of pharmaceutical proteins at high levels of greater than about 10 pg/cell/day. Id. The Examiner concludes that a skilled artisan would have had a reasonable expectation of success, with a reasonable level of predictability, and would be motivated to combine the teachings of the references. The Examiner reasons that this is so, because a skilled artisan would understand that (1) Meade teaches that the alpha-lactalbumin signal sequence can be operably linked to decorin to target its expression in host cells; (2) Do teaches alpha lactalbumin fusion to glycoproteins aids in protein expression; (3) von Marschall teaches that the leader sequence of human decorin is processed and cleaved off in the cell; and (4) Bremel teaches that production of proteins in host cells, such as CHO cells, containing multiple integrated copies of a retroviral integrating vector containing promoters such as alpha lactalbumin are useful for the production of pharmaceutical proteins at high levels of greater than about 10 pg/cell/day. Id. at 7. Therefore, the Examiner concludes, the claimed invention would have been prima facie obvious to one of ordinary skill in the art at the time of invention. Id. Appellant argues that, as the Examiner acknowledges, Ruoslahti I does not teach the use of retroviral vectors or the claimed signal sequence. App. Br. 7. Appellant asserts that nothing in the prior art would have led a person of ordinary skill in the art to identify Ruoslahti I as the lead prior art Appeal 2019-006293 Application 13/419,045 8 or would have motivated such a person to make specific modifications to Ruoslahti I (viz., use of retroviral vectors and the claimed signal sequence in the Ruoslahti I process) to make the invention. Id. (citing Procter & Gamble Co. v. Teva Pharms. USA, Inc., 566 F.3d 989 (Fed. Cir. 2009) and Daiichi Sankyo Co., Ltd v. Matrix Labs, Ltd., 619 F.3d 1346 (Fed. Cir. 2010)). Specifically, Appellant asserts, given the state of the art in 2010, a skilled artisan would not have looked to Ruoslahti I, because Ruoslahti personally stated in 2010 that the previously described methods for producing decorin had been insufficient for producing clinically useful amounts of decorin. Id. According to Appellant, at the time the invention was made, the art was looking away from expression of decorin as a stand-alone protein and was instead attempting to target decorin via a “coxsackie adenovirus receptor” (“CAR”) protein system due to problems with decorin production. Id. Appellant points to the Declaration of Dr. Gregory Bleck3 (the “Bleck Declaration”) as establishing that the art at the time of invention had tried and failed to solve the problem, notwithstanding presumed knowledge of the references cited by the Examiner. App. Br. 7. Appellant notes that each of the Examiner’s four rejections in the appeal before us relies at least on a base combination of Ruoslahti I, Meade, and Bremel. Id. Appellant contends that the evidence presented in the Bleck Declaration establishes that Dr. Ruoslahti is a pioneer in the biology of decorin and has published extensively upon that subject. Id. (citing Bleck Decl. ¶ 4). However, Dr. Bleck testifies that, 20 years after the publication of Ruoslahti I, and 10 years after the publication of Meade and Bremel, Dr. Ruoslahti observed in a 3 Dr. Bleck is one of the named inventors. Appeal 2019-006293 Application 13/419,045 9 peer-reviewed publication that decorin had not yet reached the clinic because of difficulties in production, stating that: Despite the positive results in animal models, decorin has not reached the clinic. One reason is that as a protein therapeutic, it is relatively difficult to manufacture. Enhancing the activity of decorin is a potential solution to this problem, as it would make it possible to achieve the same result with a lower dosage. Id. at 7–8 (citing Bleck Decl. ¶ 4 (quoting T.A.H. Järvinen et al., Target- Seeking Antifibrotic Compound Enhances Wound Healing and Suppresses Scar Formation in Mice, 107(50) PNAS 21671–76 (2010) (“Järvinen”) (internal citations omitted))). Appellant notes that Dr. Bleck further opines that, instead of employing CHO cells to manufacture decorin, as taught by Ruoslahti I, transgenic animal milk, as taught by Meade, or a retroviral expression system, as taught in Bremel, Dr. Ruoslahti used a complicated fusion with a CAR peptide to target decorin, so that lower dosages could be employed. App. Br. 8 (citing Bleck Decl. ¶ 6). Similarly, argues Appellant, Dr. Ruoslahti did not use any of the many commercial expression systems available in 2010 for the expression of decorin core protein or glycosylated decorin. Id. Appellant asserts that, based upon the prior art as a whole, it would have been evident to a skilled artisan in 2010 that there would not have been a reasonable expectation of success in obtaining high-level expression (i.e., greater than 10 picograms/cell/day) of decorin core protein in any expression system. Appellant further asserts that there likewise would have been no reason to expect that the retroviral expression system recited in the claims would be better than any of the expression systems used Appeal 2019-006293 Application 13/419,045 10 for the twenty years prior to 2010, all of which had failed to produce sufficient amounts of decorin for clinical use. Id. (citing Bleck Decl. ¶ 7). Appellant points to the analysis set forth in KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007), which requires identifying a starting reference point or points “in the art, prior to the time of invention, from which a skilled artisan might identify a problem and pursue potential solutions. App. Br. 8 (quoting Eisai Co. Ltd v. Dr. Reddy’s Labs., Ltd., 533 F.3d 1353, 1359 (Fed. Cir. 2008)). Appellant argues that, to the contrary, the state of the art in 2010 was such that contemporaneous methods to produce clinically sufficient amounts of decorin were unsuccessful. Id. Appellant asserts that, against this background, to solve the problem of decorin production, a person of ordinary skill in the art could have tried a potentially infinite combination of expression systems and vectors, signal sequences, host cells, etc., in attempting to produce decorin in clinically useful amounts. Id. Therefore, Appellant contends, the prior art provides no reason as to why a skilled artisan would have narrowed the prior art universe to the use of the claimed expression system for the production of decorin. Id. The Examiner responds that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. Ans. 16 (citing, e.g., In re Keller, 642 F.2d 413, 426 (C.C.P.A. 1981)). The Examiner finds that Appellant’s arguments are apparently based upon the premise that the claims are not obvious because they are not anticipated, however, the Examiner notes, lack of anticipation is not evidence of non-obviousness. Id. The Examiner finds that Appellant’s arguments do not apply the appropriate standard for obviousness, because obviousness does not rely Appeal 2019-006293 Application 13/419,045 11 upon what a single researcher has done or attempted to do in expressing a protein. Ans. 17. Rather, explains the Examiner, the standard of obviousness relies upon whether the differences that exist between the claims and the closest prior art would have been obvious to one of ordinary skill in the art based on the prior art as a whole. Id. (citing KSR, 550 U.S. at 415–21). It is the Examiner’s position that it would have been predictable for a person of ordinary skill in the art to combine and substitute the proteins of Bremel with the decorin proteins of Ruoslahti I, and to use retroviral vectors for the expression of recombinant decorin, with a high level of predictability and a reasonable expectation of success. App. Br. 17. The Examiner finds that Bremel acknowledges that these retroviral vectors overcome the problem of stability and the expression of recombinant proteins in mammalian cell lines, and would increase the expression of the recombinant proteins to high levels. Id. at 17–18. The Examiner reasons that, given that Bremel is focused on high level expression of therapeutic proteins, and because decorin is a therapeutic protein, one of ordinary skill in the art would have had a reasonable expectation of success in applying the techniques of Bremel to the decorin proteins of Ruoslahti I. Id. at 18. The Examiner notes that Bremel acknowledges that production of proteins in host cells, such as CHO cells, containing multiple integrated copies of a retroviral-integrating vector with promoters such as alpha lactalbumin, are useful for the production of pharmaceutical proteins at high levels of greater than about 10 pg/cell/day. Ans. 18. The Examiner further finds that Bremel also acknowledges the problem, taught by Järvinen, of generating stable cell lines and production of high expression levels of Appeal 2019-006293 Application 13/419,045 12 recombinant protein for therapeutic purposes. Id. (citing Bremel cols. 1–2, ll. 46–11). The Examiner finds that Bremel remedies this perceived problem through multiple integration of copies of a retroviral integrating vector containing promoters such as alpha lactalbumin to produce high levels of recombinant protein. Id. The Examiner concludes that the preponderance of the evidence in the prior art outweighs the opinions presented in the Bleck Declaration. Ans. 18–19. The Examiner finds that although Dr. Ruoslahti was admittedly a pioneer in the field, he did not use any of the many commercial expression systems available in 2010 for expression of decorin core protein or glycosylated decorin. Id. at 19. The Examiner concludes that Dr. Bleck’s opinion that a person of ordinary skill in the art would not have had a reasonable expectation of success in obtaining high-level expression of decorin core protein, amounts to an opinion unsupported by a factual basis. Id. We are also not persuaded by Appellant’s arguments. As an initial matter, we disagree with the Examiner’s standard of obviousness. KSR holds that Section 103: [F]orbids issuance of a patent when “the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. KSR, 550 U.S. at 399. Nevertheless, we find that Appellant does not contest the Examiner’s findings that the cited prior art teaches or suggests all of the limitations of the claims on appeal. Rather, Appellant contends, a person of ordinary skill Appeal 2019-006293 Application 13/419,045 13 would have had no reason to start with the teachings of Ruoslahti I, and thus would have had no motivation to combine the teachings of that reference with the other references cited by the Examiner. Furthermore, Appellant argues, given the state of the art at the time of invention, a person of ordinary skill in the art would have had no reasonable expectation of success in combining the references to produce the claimed composition “at a rate of greater than 10 picograms/cell/day when cultured,” as recited in claim 10. With respect to Appellant’s argument that a person of ordinary skill in the art would “would certainly not have started with Ruoslahti 1” (see App. Br. 7), we disagree. Ruoslahti I is directed to “a general method whereby one skilled in the art can identify proteins which can bind to cell regulatory factors or identify cell regulatory factors which bind to a certain family of proteins.” Ruoslahti I col. 8, ll. 14–17. Specifically, Ruoslahti I teaches that: [T]he invention teaches the discovery that decorin and biglycan bind TGF-ßs and MRF and that such binding can inhibit the cell regulatory functions of TGF-ßs. Further, both decorin and biglycan are about 80% homologous and contain a leucine-rich repeat of about 24 amino acids in which the arrangement of the leucine residues is conserved. Id. at col. 8, ll. 20–27. Ruoslahti I thus teaches the importance of decorin and provides motivation to a person of ordinary skill in the art to seek a way to synthesize the protein in significant quantities. Furthermore, it is logical to believe that a skilled artisan, seeking to synthesize decorin, would look initially to the teachings of a “pioneer in the biology of decorin and [one who] has published extensively on decorin,” as the Bleck Declaration admits. See Standard Oil Co. v. Am. Cyanamid Co., 774 F.2d 448, 454 Appeal 2019-006293 Application 13/419,045 14 (Fed. Cir. 1985) (holding that a person of ordinary skill in the art “thinks along the line of conventional wisdom in the art,” they are also “presumed to be aware of all the pertinent prior art”). In support of Appellant’s argument that a skilled artisan would have had no reasonable expectation of success in combining the teachings of the references, Appellant relies primarily upon the Bleck Declaration which, in turn relies primarily upon Järvinen. Dr. Bleck acknowledges that Dr. Ruoslahti “is a pioneer in the biology of decorin and has published extensively on decorin.” Bleck Decl. ¶ 4. Dr. Bleck then points to Järvinen (of which Dr. Ruoslahti is a co-author), which states that: “Despite the positive results in animal models, decorin has not reached the clinic. One reason is that as a protein therapeutic, it is relatively difficult to manufacture.” Id. (quoting Järvinen 21671 (internal citations omitted)). Appellant points out that Järvinen, which was published in 2010, describes the state of the art considerably after the filing of Ruoslahti I, which was filed in 1995 and Bremel, which was filed in 2001. However, Järvinen states that, due to the relative difficulty of manufacturing decorin as a protein therapeutic, decorin “has not reached the clinic.” We interpret this latter phrase to mean that, as of 2010, the difficulties of manufacturing pharmaceutical decorin prevented it from being produced at a scale suitable for clinical trials regarding efficacy to be carried out in humans, which involves trials in large patient groups. However, such a scaled-up level of production, with its attendant difficulties, is not recited by the claims on appeal, which require only that cultured host CHO cells “secrete[ ] non-gagylated mature decorin core protein at a rate of greater than 10 picograms/cell/day….” Appeal 2019-006293 Application 13/419,045 15 Bremel teaches: [T]he production of proteins in host cells, and, more particularly to host cells containing multiple integrated copies of an integrating vector. Suitable integrating vectors for use in the present invention include retrovirus vectors, lentivirus vectors, transposon vectors, and adeno-associated virus vectors.… by using the integrating vectors at a high multiplicity of infection. The host cells are useful for producing pharmaceutical proteins, variants of proteins for use in screening assays, and for direct use in high throughput screening. Bremel Abstr. (emphasis added). Specifically, Bremel teaches: The present invention further provides a method of producing a protein of interest comprising: 1) providing a host cell comprising a genome, the genome comprising at least two integrated copies of at least one integrating vector comprising an exogenous gene operably linked to a promotor, wherein the exogenous gene encodes a protein of interest, and 2) culturing the host cells under conditions such that the protein of interest is produced. In some preferred embodiments, the integrating vector further comprises a secretion signal sequence operably linked to said exogenous gene. In other embodiments, the methods further comprise step 3) isolating the protein of interest. Id. at col. 4, ll. 25–36. Bremel also teaches that: In some embodiments of the present invention, the promoter is selected from the group consisting of the alpha-lactalbumin promoter, cytomegalovirus promoter and the long terminal repeat of Moloney murine leukemia virus. In other preferred embodiments, the integrating vectors further comprise a secretion signal operably linked to the exogenous gene. Id. at cols 2–3, ll. 65–4. Finally, Bremel teaches, in its Examples, protein yields of 22.5 pg/cell/day. See id. at Ex. 7. We agree with the Examiner (and Appellant does not contest), that the remaining references teach the remaining limitations of the claims. Most Appeal 2019-006293 Application 13/419,045 16 importantly, aside from noting the lack of manufacture at clinical testing scale in Järvinen, Appellant provides no fact-based reason why a person of skill in the art would have arrived at the conclusion that combining the teachings of the cited references could not reasonably be expected to work to achieve the production of decorin from a cultured CHO cell at a rate of greater than 10 picograms/cell/day. We accord due deference to the quoted statement in Järvinen, but neither Järvinen nor Appellant tells us what is meant by “relative difficulty” in manufacturing decorin, what is difficult, or how, or if that difficulty in manufacturing decorin at the clinical-level relates to why one of ordinary skill in the art would not have combined the teachings of the references cited by the Examiner. Absent any such evidence or reasoning, we do not agree with Appellant that a skilled artisan would not have had a reasonable expectation of success. Appellant also argues that the Examiner’s reliance upon In re Wright, 569 F.2d 1124 (C.C.P.A. 1977) is inapposite, and that Wright supports the non-obviousness of the claims. App. Br. 9. Specifically, Appellant points to the Examiner’s reasoning that Appellant’s “contentions that the reference patents are old are not impressive absent a showing that the art tried and failed to solve the same problem notwithstanding its presumed knowledge of the references.” Id. (quoting Non-Final Act. 16 (citing Wright)). Appellant contends that Dr. Bleck’s testimony in his Declaration establishes that the art tried, and failed, to solve the problem of decorin production as a stand-alone protein, notwithstanding the teachings of the references. App. Br. 9–10. Appellant points out that each of the four rejections relies at least on a combination of Ruoslahti I, Meade, and Bremel. Appellant asserts that Dr. Bleck’s testimony that, despite the fact Appeal 2019-006293 Application 13/419,045 17 that Dr. Ruoslahti is a pioneer in the biology of decorin, even years after the publication of Ruoslahti I, Meade, and Bremel references, Järvinen teaches that decorin had not reached the clinic because of difficulties in production. Id. at 10. We do not find this persuasive for the reasons we have already explained. Appellant has not provided any evidence or argument as to why the difficulties in producing decorin at clinical trial levels would persuade a person of ordinary skill in the art that there could be no reasonable expectation of success in combining the teachings of the references to obtain cultured host CHO cells that “secrete[ ] non-gagylated mature decorin core protein at a rate of greater than 10 picograms/cell/day….” Absent any such evidence or argument, we do not find Appellant’s reliance upon Wright as showing why the claims are not obvious to be persuasive. Finally, Appellant argues that the Examiner erred by not properly considering the evidence presented in the Bleck Declaration. App. Br. 10. Appellant contends that Dr. Bleck’s statements are based on the statements made by Järvinen, and further based on Dr. Bleck’s experience in the field. Id. at 11. Appellant asserts that the Examiner has failed to consider, or failed to give any weight, to this evidence, and the related testimony by Dr. Bleck. Id. We disagree. The Examiner, in a prior Final Office Action, stated that: In the instant case, it is the examiner’s position that the preponderance of the evidence in the prior art [see rejection above and preceding paragraph] outweighs the opinions presented in the declarations that because “the pioneer in the field. Dr. Ruoslahti, did not use any of the many commercial expression systems available in 2010 for expression Appeal 2019-006293 Application 13/419,045 18 of decorin core protein or glycosylated decorin, it is apparent to a person of ordinary skill in the art that there was not a reasonable expectation of success for high level expression of decorin core protein”, which lacks factual evidence. Final Act. 17 (filed December 21, 2017. It is evident from this that the Examiner weighed the testimony of Dr. Bleck against the teachings of the prior art and finds the latter persuasive. We have explained why we are not persuaded by Appellant’s arguments and why we agree with the Examiner’s findings and conclusions. We consequently affirm the Examiner’s rejections of the claims. CONCLUSION The Examiner’s rejection of claims 10–12 and 17–25 under 35 U.S.C. § 103 is affirmed. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136. AFFIRMED Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 10 103 Ruoslahti I, Meade, Do, von Marschall, Bremel 10 11, 12, 19, 25 103 Ruoslahti I, Meade, Do, von Marschall, Bremel, Pang 11, 12, 19, 25 Appeal 2019-006293 Application 13/419,045 19 17, 18, 20, 21 103 Ruoslahti I, Meade, Do, von Marschall, Bremel, Pang, Ohigashi 17, 18, 20, 21 22–24 103 Ruoslahti I, Meade, Do, von Marschall, Bremel, Pang, Ohigashi, Hasslacher 22–24 Overall Outcome 10–12, 17–25 Copy with citationCopy as parenthetical citation