THE REGENTS OF THE UNIVERSITY OF CALIFORNIADownload PDFPatent Trials and Appeals BoardOct 29, 202013891562 - (D) (P.T.A.B. Oct. 29, 2020) 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. 13/891,562 05/10/2013 Karen Christman 24978-0213 1030 29052 7590 10/29/2020 EVERSHEDS SUTHERLAND (US) LLP 999 PEACHTREE STREET, N.E. SUITE 2300 ATLANTA, GA 30309 EXAMINER KIM, TAEYOON ART UNIT PAPER NUMBER 1632 NOTIFICATION DATE DELIVERY MODE 10/29/2020 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): patentdocket@eversheds-sutherland.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte KAREN CHRISTMAN, JENNIFER SINGELYN, and JESSICA DEQUACH __________ Appeal 2020-002061 Application 13/891,562 Technology Center 1600 __________ Before DONALD E. ADAMS, FRANCISCO C. PRATS, and JEFFREY N. FREDMAN, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a catheter based administration method for cardiac tissue repair or regeneration. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the Real Party in Interest as the Regents of the University of California (see Appeal Br. 2). 2 We have considered the Specification of May 10, 2013 (“Spec.”); Non- Final Office Action of Aug. 10, 2018 (“Non-Final Action”); Appeal Brief of Sept. 11, 2019 (“Appeal Br.”); and Examiner’s Answer of Nov. 19, 2019 (“Ans.”). Appeal 2020-002061 Application 13/891,562 2 Statement of the Case Background “The most common cause of cardiovascular disease is myocardial infarction (Ml), which occurs when a coronary artery is occluded. MI results in the death of cardiomyocytes and extracellular matrix (ECM) degradation, followed by scar tissue deposition. Eventually heart failure is onset” (Spec. ¶ 4). “Current efforts to prevent heart failure after myocardial infarction have focused on cellular transplantation to replace necrotic cardiomyocytes, prevent negative left ventricular remodeling, and regenerate heart tissue. However, without the proper matrix, cardiomyocyte growth in vitro and survival in vivo have been poor” (id. ¶ 7). The Specification teaches “a composition comprising decellularized extracellular matrix derived from cardiac tissue” (id. ¶ 8). The Claims Claims 21, 27–32, 34, 35, 37–39, 44, 45, and 47–52 are on appeal. Claim 21 is representative and reads as follows: 21. A catheter based administration method for cardiac tissue repair or regeneration in a subject in need thereof, comprising delivering 2–8 mg/mL of decellularized extracellular matrix derived from cardiac muscle tissue to ischemic cardiac tissue within said subject through a catheter and catheter needle having a gauge 27G, 28G, 29G, or 30G, wherein the decellularized extracellular matrix transitions to a gel form in vivo after delivery through the catheter and catheter needle to the ischemic cardiac tissue. Appeal 2020-002061 Application 13/891,562 3 The Rejection The Examiner rejected claims 21, 27–32, 34, 35, 37–39, 44, 45, and 47–52 under U.S.C. § 103(a) as obvious over Badylak,3 Freyman,4 Kornowski,5 PuraMatrix,6 and Klein7 (Ans. 3–8). The Examiner finds Badylak teaches “administering a solubilized extracellular matrix (ECM) composition to a patient in an un-gelled form prior to gelation where the composition gels in situ . . . and the ECM is decellularized after isolation from the tissue of interest” (Ans. 4). The Examiner finds Badylak teaches “(urinary bladder matrix) concentration is around 3–6 mg/ml” (id. at 5). The Examiner acknowledges that Badylak does not “teach the method for cardiac tissue repair or the ECM being delivered to an ischemic cardiac tissue of a subject” or “the concentration of decellularized ECM from cardiac muscle tissue” (id. at 4, 5). The Examiner finds Freyman teaches “the use of decellularized ECM for treating diseased, defected, damaged or ischemic tissue or organ including heart valves, myocardium, pericardium” and also teaches “cardiac 3 Badylak et al., US 2008/0260831 A1, published Oct. 23, 2008. 4 Freyman et al., US 2005/0181016 A1, published Aug. 18, 2005. 5 Kornowski et al., Electromagnetic Guidance for Catheter-Based Transendocardial Injection: A Platform for Intramyocardial Angiogenesis Therapy, 35 J. Am. College Cardiology 1031–9 (2000). 6 PuraMatrix, 3DM Inc., WWW.Puramatrix.com, 1–3 (2005). The Examiner refers to this reference as “PuraMatrix” and Appellant refers to the reference as 3DM (see, e.g., Ans. 4, Appeal Br. 3). We will refer to this reference as “PuraMatrix.” 7 Klein et al., Injectible Collagen in Tissue Augmentation in Clinical Practice 63–82 (Taylor & Francis 2006, first edition). Appeal 2020-002061 Application 13/891,562 4 muscle tissue is a source of decellularized ECM” (id.). The Examiner finds Kornowski teaches “the use of a catheter-based needle (27G) for intramyocardial injection for treating an ischemic heart” (id. at 5–6). The Examiner finds PuraMatrix teaches “hydrogel can be injected into a tissue using 30G needle” (id. at 6). Finally, the Examiner finds that Klein teaches “Zyderm collagen (ZC) can be injected using a 30- or 32-gauge needle when it is stored at 4°C” (id. at 6). The Examiner finds it obvious to “combine the teachings of Badylak et al. with the teachings of Freyman et al. because since both teachings are directed to the use of decellularized ECM isolated from cardiac tissue” (Ans. 4–5). The Examiner further finds it obvious to “determine a suitable concentration of a decellularized ECM derived from cardiac muscle tissue that can be gelled in vivo” (id. at 5). The Examiner also finds Kornowski renders it obvious “to use a catheter-based transendocardial injection using a 27G needle” as a known equivalent (id. at 5–6). The issue with respect to this rejection is: Does a preponderance of the evidence of record support the Examiner’s conclusion that Badylak, Freyman, Kornowski, PuraMatrix, and Klein render the claims obvious? Findings of Fact 1. Badylak teaches “methods for preparing gelled, solubilized extracellular matrix (ECM) compositions useful as cell growth scaffolds” that can be “administered to a patient in an un-gelled form prior to gelation where the composition gels in situ” (Badylak ¶ 12). 2. Badylak teaches a process for preparation of cardiac ECM (see Badylak ¶ 91). Appeal 2020-002061 Application 13/891,562 5 3. Badylak teaches that after “isolation of the tissue of interest, decellularization is performed by various methods” (Badylak ¶ 50). 4. Badylak teaches the composition is injected as a pre-gel into a patient. The composition is injected at a locus in the patient where the matrix is needed for cell growth. For example and without limitation, where a patient has had tissue removed due to trauma . . . [T]he composition can be injected at the site of tissue removal to facilitate in-growth of tissue. The viscosity of the pre-gel can be controlled by varying the amounts of water (e.g., by varying the amounts of water, acid, base, buffer (such as PBS) or other diluents) used to prepare the pre-gel. In applications in which a small gauge needle is used, such as in endoscopy, a less viscous pre-gel would be needed, which typically results in a less viscous gel, once the pre-gel is gelled. In applications in which a larger gauge needle is available, a more viscous gel, with higher strength when gelled, can be used. (Badylak ¶ 70). 5. Badylak teaches exemplary ECM concentrations, specifically “[c]ollagen type I gels at a concentration of 3 mg/ml became more turbid following gelation than UBM-gel at a concentration of 3 mg/ml and 6 mg/ml” (Badylak ¶ 119). Badylak teaches that: ECM powder suspended in saline and UBM gels were tested side by side to see if they could successfully pass through injection needles frequently used in medical procedures such as vocal cord augmentation. These needles had 1 cm long, 25 gauge caliber tips that are attached to 25 cm long, 16 gauge needle shafts. UBM gels easily and consistently passed through these needles. The UBM powder suspension had an upper limit concentration of 10 mg/ml above which the needle would be frequently occluded, making it difficult to determine the actual amount of ECM delivered. This trial showed the feasibility of using the [UBM] gel as an injectable material. Appeal 2020-002061 Application 13/891,562 6 (Badylak ¶ 123). 6. Freyman teaches “decellularized extracellular matrix may be used to promote angiogenesis and/or repair, replace or regenerate cells, tissues or organs, such as but not limited to lymph vessels, blood vessels, heart valves, myocardium, pericardium, pericardial sac” (Freyman ¶ 21). 7. Freyman teaches “[b]one marrow extracellular matrix has potential therapeutic value in treating myocardial infarction” (Freyman ¶ 200). 8. Freyman teaches “[s]uitable animal body tissue from which the decellularized extracellular matrix material of the present invention is produced includes” “internal organs, such as the heart” and “[e]xamples of muscle tissue include, but are not limited to, myocardium (heart muscle)” (Freyman ¶¶ 46, 48). 9. Kornowski teaches “an injecting catheter having a 27G needle for intramyocardial delivery of potentially therapeutic agents” (Kornowski 1032, col. 1). 10. Kornowski teaches “this system should permit the routine safe transendocardial delivery of therapeutic agents into the LV myocardium. If the biologic and clinical importance of angiogenic treatment is ultimately demonstrated, the system we describe in this report may constitute an important new strategy of treating patients with myocardial ischemic syndromes” (Kornowski 1038, col. 2). 11. Klein teaches treatment with zyderm collagen (ZC) where ZC contains 95% to 98% type I collagen; the remainder is type III collagen. The collagen is suspended in phosphate-buffered physiologic saline with 0.3% lidocaine. It is provided in prefilled syringes, which are stored at a low temperature (4°C), Appeal 2020-002061 Application 13/891,562 7 so that the dispersed fibrils remain fluid and small. This allows passage of the product through a 30- or 32-gauge needle. Once implanted, the human body temperature (37°C) causes the product to undergo consolidation into a solid gel. (Klein 64). 12. PuraMatrix teaches in vivo delivery using a “needle to 26 or 30G and inject in tissue of choice” (PuraMatrix 1). Principles of Law The Examiner has the initial burden of establishing a prima facie case obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Analysis We adopt the Examiner’s findings of fact and conclusion of law (see Ans. 3–8, FF 1–12) and agree that Badylak, Freyman, Kornowski, PuraMatrix, and Klein render claim 1 obvious. We particularly agree with and adopt the Examiner’s response to arguments and to the Christman Declaration.8 We address Appellant’s arguments below. Appellant contends: There is no reason to combine Kornowski with Badylak or Freyman. The Applicant respectfully disagrees that the Examiner demonstrates that these references would be obvious to combine. In particular, the Examiner states, “Badylak et. al. do not particularly teach the method for cardiac tissue repair of the ECM being delivered to an ischemic cardiac tissue of a 8 Declaration of Dr. Karen Christman, dated Nov. 20, 2017. Appeal 2020-002061 Application 13/891,562 8 subject.” (See Office Action at p. 3, para. 4). The Examiner later states “Kornowski does not teach a ‘viscous’ solution” (See Office Action at p. 8, para. 3). Therefore, how could it be obvious to one skilled in the art to combine these references when they are in completely different fields of study (ECM manufacturing, and stem cell delivery)? (Appeal Br. 4). We find this argument unpersuasive because in an obviousness analysis, “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 550 U.S. at 417). Here, Badylak teaches methods of preparing decellularized ECM compositions, including cardiac ECM, in un-gelled form that are delivered to the location where cell growth is needed and then gel in situ (FF 1–3). Freyman also teaches preparing ECM from heart tissue (FF 8) and explains “decellularized extracellular matrix may be used to promote angiogenesis and/or repair, replace or regenerate cells, tissues or organs, such as but not limited to . . . heart valves, myocardium, pericardium” (FF 6). Thus, the ordinary artisan would have had reason to apply Badylak’s cardiac ECM to treatment of cardiac tissues in order to promote blood vessel growth (angiogenesis) or to replace damaged cardiac tissues (FF 1–3, 6–8). Badylak also teaches that “the composition is injected as a pre-gel into a patient. The composition is injected at a locus in the patient where the matrix is needed for cell growth” and that this injection may be performed using either a small gauge or large gauge needle depending upon the optimized gel viscosity (FF 4) including a 25G needle (FF 5). Kornowski evidences that one particular gauge of needle, 27G gauge needles, may be used for intramyocardial delivery (FF 9). Kornowski specifically teaches the “routine safe transendocardial delivery of therapeutic agents into the LV Appeal 2020-002061 Application 13/891,562 9 myocardium” (FF 10). Thus, an ordinary artisan interested in delivery of the cardiac ECM of Badylak or Freyman using various gauge needles as taught by Badylak would have had reason to select the 27G gauge needle of Kornowski because it would be routine and safe (FF 1–4, 6, 9, 10). Appellant contends “there is no clear rationale for combining the references with Korn[o]kowski considering the physical differences and the completely different research fields as compared to the Badylak and Freyman references” (Appeal Br. 45). We interpret this argument as asserting that Kornowski is non- analogous art to Badylak and Freyman and find the argument unpersuasive. “Prior art is analogous if it is from the same field of endeavor or if it is reasonably pertinent to the particular problem the inventor is trying to solve.” Circuit Check Inc. v. QXQ Inc., 795 F.3d 1331, 1335 (Fed. Cir. 2015). Under either test, Kornowski is reasonably understood as analogous to Badylak and Freyman. All three references are in the field of endeavor of delivering pharmaceutical materials to heart tissue for therapeutic purposes (FF 4, 6, 9, 10). Even if these references were not in the same field of endeavor, Kornowski’s teaching that 27G needles are a safe and routine way to deliver un-gelled treatment materials to the heart would have been directly pertinent to Freyman who teaches treatment of cardiac tissue with ECM (FF 6) and to Badylak who teaches delivery of un-gelled ECM using various gauge needles to trauma locations (FF 4). An ordinary artisan, considering which specific gauges of needles to use based on Badylak’s treatment would have reasonably looked to Kornowski’s teaching as a guide for needles useful in treatment of cardiac tissue. Appeal 2020-002061 Application 13/891,562 10 Appellant contends: It is erroneous to find that one skilled in the art would have been motivated to combine the method of Badylak with the catheter-based injection of Kornowski and a 30G needle of 3DM. In particular, the 3DM reference has no bearing on this application, as it does not describe an ECM hydrogel. Hydrogel is a generic scientific term for a gel-like substance that contains water. As described above, biomaterial compositions vary widely and to assume that one hydrogel with completely different components would behave the same as an ECM hydrogel is flatly erroneous. (Appeal Br. 5). We find this argument unpersuasive because the Examiner has already demonstrated that Badylak teaches the use of a variety of different needles for delivery of the un-gelled ECM (FF 4) and Kornowski teaches that 27G needles may be used for delivery of therapeutics to cardiac tissue (FF 9). PuraMatrix is simply further evidence showing that un-gelled materials may be administered through 30 or 32 gauge needles prior to forming gels in the human body (FF 11). As KSR explains, “if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill.” KSR, 550 U.S. at 417. Here, PuraMatrix supports the Examiner’s position by providing further support for Badylak’s teaching that un-gelled materials such as un-gelled ECM may be administered through smaller needle gauges such as 30G needles (FF 4, 11). Appellant contends a person of ordinary skill looking to modify the method disclosed in Badylak for delivery of hydrogels would look to methods of delivering viscous solutions. In contrast, Kornowski relates to Appeal 2020-002061 Application 13/891,562 11 delivering adenoviral vectors in a 3% sucrose solution, which is a low viscosity solution having a viscosity of 1.081 relative to water, using a catheter-based transendocardial injection using a 27G needle. (Kornowski, p. 1033, col. 2, para. 2.) Cardiac catheters, as used in Kornowski, typically are ~1 m in length. (See “Christman Declaration” filed on November 27, 2017, Appendix 2C.) (Appeal Br. 6). Appellant therefore contends the ordinary artisan would expect Badylak’s “catheter and/or needle would become occluded with the ECM when pushing concentrations of ECM needed to form a gel in vivo through the length of the catheter, and as such the ECM of Badylak could not reasonably be expected to travel through a long cardiac catheter without significant dilution” (id.). We are not persuaded for several reasons. First, none of the claims impose any specific length requirement on the catheter or needle, and Appellant provides no evidence showing that only meter long needles function to reach the heart. “[A]ppellant’s arguments fail from the outset because . . . they are not based on limitations appearing in the claims.”). In re Self, 671 F.2d 1344, 1348 (CCPA 1982). Indeed, Badylak teaches the use of 25 cm long needles (FF 5), and Appellant provides no explanation why that length would be insufficient to administer the obvious ECM composition to a human heart. Second, we have considered the inventor Declaration of Dr. Christman, but she also asserts the requirement for longer catheters that is not recited in any of the pending claims (see, e.g., Christman Decl. ¶ 7). We are also unpersuaded by Dr. Christman’s assertion that “there is no reasonable expectation that a decellularized cardiac ECM at a concentration of 2-8 mg/ml would pass through a cardiac catheter with a 27G needle and Appeal 2020-002061 Application 13/891,562 12 form a gel in vivo” (Christman Decl. ¶ 8). The evidence of record does not support Dr. Christman’s statement. Badylak specifically teaches that UBM “easily and consistently passed through” 25G needles in concentrations of 3 mg/ml and 6 mg/ml that fall within the claimed range (FF 5). Badylak teaches that only at concentrations above 10 mg/ml was occlusion a problem (FF 5). Moreover, Klein evidences that smaller 30G and 32G needles functioned to allow passage of un-gelled Zyderm II material that is up to 6.5% gelling material (FF 11; Klein 64). Similarly, Appellant provides no persuasive evidence that the other concerns of higher pressure or issues would impede the use of Badylak’s material at 3 mg/ml using 27G needles. We note that Appellant provides no comparative evidence showing that the prior art Badylak composition would not pass through a 27G needle, instead rebutting the evidence of record with the calculation that “the difference in pressure change through a 27G needle versus a 25G needle is greater than 50%” (Christman Decl. ¶ 6). However, the more than 50% reduction in viscosity from the highest claimed 8 mg/ml value to the 3 mg/ml value disclosed by Badylak reasonably supports an understanding that Badylak’s un-gelled 3 mg/ml ECM composition would be expected to pass through a 27G needle (FF 4). Appellant contends a person skilled in the art, starting with Badylak, would not look to Kornowski or 3DM or Klein to modify the method of delivery of the ECM to ischemic tissue of a subject for cardiac tissue repair of Badylak, because Badylak provides no teaching or motivation to do so. In fact, Badylak discloses concerns regarding the limitations arising as a result of the viscosity of the ECM, and as such teaches away from modifying the method in ways that would adversely affect these limitations (i.e. increase length and decrease bore size of needle). There are Appeal 2020-002061 Application 13/891,562 13 countless possible ways of delivery and numerous needle bore sizes and lengths. The Appellant asserts that all of these choices are not all equivalent. The surprising technical success of combining a smaller needle bore size and using a catheter for delivery, while maintaining control and precision of delivery, provides a method that can advantageously be used over prior methods for cardiac tissue repair or regeneration. (Appeal Br. 7). We find these arguments unpersuasive for several reasons. “We start from the self-evident proposition that mankind, in particular, inventors, strive to improve that which already exists.” Pro–Mold & Tool Co., Inc. v. Great Lakes Plastics, Inc., 75 F.3d 1568, 1573 (Fed. Cir. 1996). As discussed above, Badylak suggests the use of un-gelled decellularized cardiac ECM for treatment of damaged tissue (FF 1–4) using concentrations as low as 3 mg/ml and needles as small as 25G (FF 5). Freyman explains that ECM may have “therapeutic value in treating myocardial infarction” (FF 7) and the ordinary artisan would have therefore found it obvious to apply Badylak’s un-gelled decellularized cardiac ECM to repair organs including heart valves, myocardium and pericardium (FF 6) for the expected therapeutic improvement in these tissues due to cell repair. As also noted, the ordinary artisan, interested in delivering the cells using smaller needles because Kornowski teaches that 27G needles are suitable for intramyocardial delivery of agents (FF 9). We are not persuaded by Appellant’s argument that Badylak teaches away from the use of a 27G needle. Badylak does not criticize, discredit, or otherwise discourage the use of a 27G needle (FF 5). “The prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, Appeal 2020-002061 Application 13/891,562 14 discredit, or otherwise discourage the solution claimed.” In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). As to Badylak’s teaching that amounts of 10 mg/ml or larger occlude the 25G needle, Badylak also teaches that 3 mg/ml and 6 mg/ml “easily and consistently passed through these needles” (FF 5). Because the claims encompass these lower values and not the less effective 10 mg/ml concentrations, there is no teaching away from the concentrations recited in the claims. And to the extent that viscosity is an issue, Badylak teaches the viscosity can be controlled by a variety of measures (FF 4) and Klein teaches that using reduced temperatures also allows improved fluidity (FF 11). Thus, the ordinary artisan, concerned with gel fluidity, would have had a number of optimizable parameters available to achieve administration as required by the claims. Lastly, to the extent that Appellant is asserting “surprising technical success” as a secondary consideration, Appellant has not demonstrated that i. the result is unexpected, because it is only in the Attorney’s arguments that the results are identified as unexpected (“[I]t is not enough to show that results are obtained which differ from those obtained in the prior art: that difference must be shown to be an unexpected difference” In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972)); ii. that a comparison of the claims to the closest prior art of Badylak shows any differences (“[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991)); iii. and has not shown a result commensurate in scope with the claims (Unexpected results must be “commensurate in scope with the degree of Appeal 2020-002061 Application 13/891,562 15 protection sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005)). Appellant contends Without the blueprint drawn by Appellant, there is no reason for a skilled artisan to look to Kornowski and 3DM and Klein, and bootstrapping the teachings of a secondary reference as justification for using the secondary reference does not explain why a skilled artisan would know to look at the secondary reference in the first instance. (Appeal Br. 8). We are not persuaded. While we are aware that hindsight bias may plague determinations of obviousness, Graham v. John Deere Co., 383 U.S. 1, 36 (1966), we are also mindful that the Supreme Court has clearly stated that the “combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR, 550 U.S. at 416. We, and the Examiner, have provided extensive reasoning explaining why the ordinary artisan, motivated by Freyman to apply Badylak’s un-gelled cardiac ECM to treatment of cardiac tissue, would have used needle sizes known by Klein and Kornowski to be functional in administering active agents to cardiac tissue that were also known to function in administering un-gelled materials that gel inside the human body, as also evidenced by PuraMatrix (FF 1–12). The combination of these known elements predictably allows administration of Badylak’s un- gelled cardiac ECM to cardiac tissue using 27G needles. Conclusion of Law A preponderance of the evidence of record support the Examiner’s conclusion that Badylak, Freyman, Kornowski, PuraMatrix, and Klein render the claims obvious. Appeal 2020-002061 Application 13/891,562 16 SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 21, 27–32, 34, 35, 37–39, 44, 45, 47–52 103 Badylak, Freyman, Kornowski, PuraMatrix, Klein 21, 27–32, 34, 35, 37– 39, 44, 45, 47–52 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 Copy with citationCopy as parenthetical citation