Yale University

Patent Trials and Appeals Board

Jan 5, 2022

2021001281 (P.T.A.B. Jan. 5, 2022)

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. 15/850,364 12/21/2017 Christopher Breuer NWCH 2015-034 DIV 6214 23579 7590 01/05/2022 PABST PATENT GROUP LLP 1355 PEACHTREE STREET NE SUITE 800 ATLANTA, GA 30309 EXAMINER GAMETT, DANIEL C ART UNIT PAPER NUMBER 1647 NOTIFICATION DATE DELIVERY MODE 01/05/2022 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@pabstpatent.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte CHRISTOPHER BREUER, THEMIS KYRIAKIDES, and JASON ROH ____________ Appeal 2021-001281 Application 15/850,364 Technology Center 1600 ____________ Before DONALD E. ADAMS, TAWEN CHANG, and RYAN H. FLAX, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s decision to reject claims 11, 13-18, and 20-33 (Appeal Br. 3). We have jurisdiction under 35 U.S.C. § 6(b).2 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 “Yale University,” (Appellant’s June 15, 2020, Appeal Brief (Appeal Br.) 3). 2 An Oral Hearing was held October 7, 2021. A transcript of the Oral Hearing was entered into the record November 2, 2021. Appeal 2021-001281 Application 15/850,364 2 STATEMENT OF THE CASE Appellant’s disclosure “relates generally to compositions and methods for increasing the patency of vascular grafts, in particular vascular grafts made from biodegradable, polymeric scaffolds” (Spec.3 1). Appellant’s Claims 11, 13, 21, 23, and 27 are reproduced below: 11. A biodegradable polymeric vascular graft or conduit comprising an amount of monocyte chemoattractant protein 1 (MCP-1) effective to recruit an effective amount of host monocytes to the graft within one week of graft implantation to inhibit, or reduce stenosis, and promote neotissue formation at the site of implantation and increase the patency of the graft in the host over time relative to the patency of the graft in the absence of MCP-1. (Appeal Br. 44.) 13. The polymeric vascular graft or conduit of claim 11, wherein the biodegradable or bioabsorbable polymers are selected from the group consisting of poly(lactic acid), poly(glycolic acid), polyanhydrides, poly(ortho)esters, polyesters, polyurethanes, poly(butic acid), poly(valeric acid), poly(caprolactone), poly(hydroxyalkanoates), and poly(lactide- co-caprolactone), or combinations, blends or co-polymers thereof. (Id.) 21. The polymeric vascular graft or conduit of claim 11, wherein the MCP-1 is dispersed throughout the vascular graft or conduit. (Id. at 45.) 3 Appellant’s December 21, 2017 Specification. Appeal 2021-001281 Application 15/850,364 3 23. The polymeric vascular graft or conduit of claim 11, wherein the effective amount of MCP-1 is released from microparticles in the graft over a period of 1 to 3 days after the graft is implanted into the host. (Id. at 46.) 27. The polymeric vascular graft or conduit of claim 11, wherein the internal diameter of the graft or conduit is larger relative to the internal diameter of the graft or conduit in the absence of MCP-1 ten weeks after implantation of the graft into the host. (Id.) Grounds of rejection before this Panel for review: I. Claims 11, 13−18, and 20−33 stand rejected under 35 U.S.C. § 112(b). II. Claims 23, 27, and 28 stand rejected under 35 U.S.C. § 112(d). III. Claims 11, 13−18, and 20−33 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Mandrusov,4 Cottone,5 and Hunter.6 Rejection I: ISSUE Does the preponderance of evidence support Examiner’s conclusion that Appellant’s claims are indefinite? 4 Mandrusov et al., US 2004/0071861 A1, published Apr. 15, 2004. 5 Cottone et al., WO 2007/059253 A2, published May 24, 2007. 6 Hunter et al., US 2005/0143817 A1, published June 30, 2005. Appeal 2021-001281 Application 15/850,364 4 ANALYSIS Examiner finds that the product set forth in Appellant’s claim 11, from which Appellant’s claims 13-18 and 20-33 ultimately depend, includes limitations relating to an “amount of MCP-1 initially present in the implant and the kinetics with which an effective amount is released” (Ans.7 20). Examiner further finds that, although “monocytes are not part of the” claimed product, Appellant’s claim 11 “makes reference to the timing of monocyte recruitment” (id.). Stated differently, Examiner finds the functional limitations recited in Appellant’s claimed indefinite. We are not persuaded. Functional language does not necessarily render a claim indefinite. See In re Swinehart, 439 F.2d 210, 212 (CCPA 1971). On this record, we interpret the functional limitations of Appellant’s claimed invention as defining a property of the product, i.e., as reciting, in functional terms, the requirements of its claimed polymeric vascular graft or conduit, relating to the amount of MCP-1 present in the graft or conduit and the effect such MCP-1 amount will produce if it is implanted into a patient. We recognize that functional limitations cover all embodiments performing the recited function and, thus, “‘[f]unctional’ terminology may render a claim quite broad.” See In re Swinehart, 439 F.2d at 213. Breadth, however, “is not to be equated with indefiniteness” on this record. In re Miller, 441 F.2d 689, 693 (CCPA 1971). 7 Examiner’s September 14, 2020, Answer. Appeal 2021-001281 Application 15/850,364 5 CONCLUSION The preponderance of evidence fails to support Examiner’s conclusion that Appellant’s claims are indefinite. The rejection of claims 11, 13−18, and 20-33 under 35 U.S.C. § 112(b) is reversed. Rejection II: ISSUE Does the preponderance of evidence support Examiner’s conclusion that Appellant’s claims 23, 27, and 28 fail to further limit Appellant’s claim 11? ANALYSIS Claim 23: Appellant’s claims 11 and 23 are reproduced above. Appellant’s claim 23 depends from and further limits Appellant’s claim 11 to require that the polymeric vascular graft or conduit is configured in such a way to require that an effective amount of MCP-1 is release from microparticles in the graft over a period of 1 to 3 days after the graft is implanted into the host. For the foregoing reasons, we are not persuaded by Examiner’s conclusion that Appellant’s claim 23 fails to further limit Appellant’s claim 11 (see Ans. 18-19; cf. Appeal Br. 38 (Appellant contends that its “[c]laim 23 explicitly limits the structure of the graft and the timing of MCP-1 release”); Reply Br. 8 22-23). 8 Appellant’s November 16, 2020, Reply Brief. Appeal 2021-001281 Application 15/850,364 6 Claims 27-28: The polymeric vascular graft or conduit of Appellant’s claim 11, reproduced above, may be configured to produce any internal diameter or wall thickness ten weeks after implantation of the polymeric vascular graft or conduit into the host. In contrast, Appellant’s claims 27 and 28, reproduced above, depend from and further limit the polymeric vascular graft or conduit of Appellant’s claim 11 to require: (a) the internal diameter of the graft or conduit is larger relative to the internal diameter of the graft or conduit in the absence of MCP-1 ten weeks after implantation of the graft into the host (claim 27) and (b) the wall thickness of the graft or conduit is thinner relative to the wall thickness of the graft or conduit in the absence of MCP-1 ten weeks after implantation of the graft or conduit into the host (claim 28). Stated differently, the polymeric vascular graft or conduit of Appellant’s claims 27 and 28 is configured to produce a specifically different internal diameter or wall thickness, respectively, ten weeks after implantation of the graft or conduit into the host as compared to the recited dimension at implantation. For the foregoing reasons, we are not persuaded by Examiner’s conclusion that Appellant’s claims 27 and 28 fail to further limit Appellant’s claim 11 (see Ans. 18-19; cf. Appeal Br. 38-39; Reply Br. 23-24). CONCLUSION The preponderance of evidence fails to support Examiner’s conclusion that Appellant’s claims 23, 27, and 28 fail to further limit Appellant’s claim 11. The rejection of claims 23, 27, and 28 under 35 U.S.C. § 112(d) is reversed. Appeal 2021-001281 Application 15/850,364 7 Rejection III: Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) FF 1. Mandrusov “relates to implantable medical devices, such as stents, and a method of resolving ischemia by inducing formation of new blood vessels through angiogenesis and arteriogenesis” (Mandrusov ¶ 2). FF 2. Mandrusov discloses that “[a] stent is broadly defined to include any inter- or intra-luminal device used for the release of an active ingredient and/or for upholding the luminal patency” (Mandrusov ¶ 44). FF 3. Mandrusov’s “stent includes a tubular body having an outer surface for contacting the wall of a vessel and an inner surface. The stent also includes a first coating supported by the inner surface and containing an angiogenic substance for the release of the angiogenic substance in the vessel” (Mandrusov ¶ 7). FF 4. Mandrusov discloses that a “[s]econd coating . . . can be formed on [the] outer surface” of its stent, wherein the “second coating . . . can be an angiogenic substance that is the same as or different than the angiogenic substance contained within the first coating” (Mandrusov ¶¶ 52-53). FF 5. Mandrusov discloses that the angiogenic substances “can be deposited into the cavities in a solid form or contained in a polymeric matrix for reducing the rate of release” (Mandrusov ¶ 55). FF 6. Mandrusov claims: 1. A stent, comprising: a tubular body having an outer surface for contacting the wall of a vessel and an inner surface; Appeal 2021-001281 Application 15/850,364 8 a first coating supported by said inner surface and containing an angiogenic substance for the release of said angiogenic substance in said vessel; and a second coating supported by said outer surface and containing a therapeutic substance for applying said therapeutic substance to said wall of said vessel. (Mandrusov 5: Claim 1.) FF 7. Mandrusov discloses that its “[a]ngiogenic substances should be understood to broadly include any . . . substances that promote, stimulate or cause therapeutic angiogenesis. One of ordinary skill in the art is familiar with methods used to determine the angiogenic or arteriogenic activity of substance” and “[r]epresentative examples of angiogenic substances include . . . monocyte chemoattractant protein 1 (MCP-1)” (Mandrusov ¶ 22; see also id. at 5: Claim 4 (Mandrusov’s claim 4 depends from and further limits the angiogenic substance on the stent of Hunter’s claim 1 to, inter alia, MCP-1)). FF 8. Mandrusov discloses that MCP-1 is involved in, inter alia, monocyte homing (Mandrusov ¶ 25; see Ans. 8 (Examiner finds that Mandrusov discloses that MCP-1 attracts monocytes)). FF 9. Mandrusov discloses: The dosage or concentration of the angiogenic substance required to produce a therapeutic effect should be less than the level at which the angiogenic substance produces toxic effects and greater than the level at which non-therapeutic results are obtained. The dosage or concentration of the angiogenic substance required can depend upon factors such as the particular circumstances of the patient; the time over which the angiogenic substance administered resides at the treatment site; and if other bioactive substances are employed, the nature and type of the substance or combination of substances. Standard Appeal 2021-001281 Application 15/850,364 9 pharmacological test procedures to determine dosages are understood by one of ordinary skill in the art. (Mandrusov ¶ 50.) FF 10. Mandrusov discloses that its “stent can . . . be made from bioabsorbable . . . or biostable polymers,” wherein “[r]epresentative examples of polymers that can be used with the embodiments of . . . [Mandrusov’s disclosure] include . . . poly(L-lactic acid); polycaprolactone; . . . polyorthoester; polyanhydride; poly(glycolic acid); . . . [and] polyurethanes” (Mandrusov ¶¶ 44-45). FF 11. Cottone discloses: A medical device for implantation into vessels or luminal structures within the body is provided, which stimulates positive blood vessel remodeling. The medical device, such as a stent and a synthetic graft, is coated with a pharmaceutical composition consisting of a controlled-release matrix and one or more pharmaceutical substances for direct delivery of drugs to surrounding tissues. The coating on the medical device further comprises a ligand . . . for restoring an endothelium at the site of injury. In particular, the drug-coated stents are for use, for example, in . . . preventing or inhibiting restenosis. (Cottone, Abstr.; see also id. ¶ 32 (Cottone discloses “a medical device for implanting into the lumen of a blood vessel or an organ with a lumen, which device provides a biocompatible system for the delivery of therapeutic agents locally in a safe and controlled manner[] and . . . thereby stimulating positive blood vessel remodeling.”); id. ¶¶ 34-35 (Cottone discloses a stent for the treatment of restenosis.).) FF 12. Cottone discloses “a stent, a stent graft, a synthetic vascular graft” made of biodegradable materials, with a “coating comprising a matrix which comprises . . . [a] biodegradable synthetic material,” “which can include polyesters such as polylactic acid, polyglycolic acid or copolymers and or Appeal 2021-001281 Application 15/850,364 10 combinations thereof” (Cottone ¶¶ 36-37 and 40; see also id. ¶ 47 (Cottone discloses biodegradable materials that can be used to coat its medical device.)). FF 13. Cottone discloses that MCP-1 may be incorporated into the matrix of its device (Cottone ¶ 46). FF 14. Cottone: [P]rovide[s] a method for treating vascular disease such as restenosis and artherosclerosis, comprising administering a pharmaceutical substance locally to a patient in need of such substance. The method comprises implanting into a vessel or hollowed organ of a patient a medical device with a coating, which coating comprises a pharmaceutical composition comprising a drug or substance for inhibiting . . . restenosis, and a biocompatible, biodegradable, bioerodible, nontoxic polymer or non-polymer matrix, wherein the pharmaceutical composition comprises a slow or controlled-release formulation for the delayed release of the drug. (Cottone ¶ 53; see id. ¶ 64 (Cottone discloses “methods for treating . . . restenosis.).) FF 15. Hunter disclose, inter alia, that stents may be coated with therapeutic substances that are loaded onto biodegradable microspheres (see Hunter ¶¶ 11 and 436). ANALYSIS Examiner concludes that, before the effective filing date of Appellant’s claimed invention, the combination of Mandrusov, Cottone, and Hunter makes obvious Appellant’s claimed invention (see Ans. 4-7; see also FF 1-15). Claim 11: Appellant’s claim 11 is reproduced above. Appeal 2021-001281 Application 15/850,364 11 Mandrusov discloses a biodegradable polymeric vascular graft or conduit, i.e., stent, having a coating comprising MCP-1 on both the inner and outer surfaces of the stent (FF 1-9). Mandrusov’s coating promotes neotissue formation, i.e., angiogenesis, induces monocyte homing, releases an active ingredient, such as MCP-1, and upholds luminal patency (see id.). Mandrusov further discloses that, before the effective filing date of Appellant’s claimed invention, those of ordinary skill in this art would have known how to optimize the “dosage or concentration of the angiogenic substance required to produce a therapeutic effect,” through routine experimentation (FF 9). Cottone discloses that MCP-1 coated biodegradable stents are effective in reducing restenosis, and Hunter informs those of ordinary skill in this art that therapeutic substances formulated as microparticles may be coated onto implantable grafts (see FF 11-15). As Appellant explains, “[t]hose of ordinary skill in the art know how to extrapolate graft size and the MCP-1 amount from those used in model organisms to those for use in human adult or human pediatric patients” (Reply Br.9 21). Therefore, we are not persuaded by Appellant’s contentions regarding optimization (see, e.g., Reply Br. 16; see also Appeal Br. 22 (Appellant contends that the combination of Mandrusov, Cottone, and Hunter “is vague on the dose of the angiogenic compounds (one of which is MCP-1) incorporated on . . . its grafts”)). 9 “[T]he reply brief [is not] an opportunity to make arguments that could have been made in the principal brief on appeal to rebut the Examiner’s rejections, but were not.” Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative). Thus, we consider only those arguments in Appellant’s Reply Brief that find support in Appellant’s Appeal Brief. Appeal 2021-001281 Application 15/850,364 12 As Appellant further explains, in order “[t]o achieve replacement of the graft with neotissue, [i.e., angiogenesis, as made obvious by the combination of Mandrusov, Cottone, and Hunter,] an initial recruitment of host monocytes to the graft is required” and “is achieved by the claimed graft structured for a timed release of an effective amount of monocyte chemoattractant protein 1 (MCP-1) to recruit an effective amount of host monocytes within one week of graft implantation” (Reply Br. 4 (citing Breuer Decl. ¶¶ 8-13) (Appellant contends that “[t]he importance of timing of the MCP-1 release and controlled inflammation at the graft site are presented in detail in paragraphs 6-17 of Dr. Breuer’s Declaration.”); see also Reply Br. 16 (Appellant explains that the “absence of MCP-1 leads to reduced graft cellularity and no neotissue formation to replace the graft over time, and excessive amount of MCP-1 leads to stenosis” (emphasis added)); Reply Br. 3 (Appellant contends that “[t]he grafts falling within the scope of the claims form neotissue at the site of graft implantation over time, which replaces the implanted graft” and “[t]he grafts as claimed can replace an occluded vessel section, or create a vessel where one did not exist,” i.e., induce angiogenesis); cf. FF 1-14). Stated differently, Appellant’s explanation supports a conclusion that the recruitment of monocytes to a biodegradable polymeric vascular graft or conduit, as suggested by the combination of Mandrusov, Cottone, and Hunter, to, inter alia, induce angiogenesis, will result in the functionality required by Appellant’s claimed invention. For the foregoing reasons, we are not persuaded by Appellant’s contention that the combination of Mandrusov, Cottone, and Hunter, does not describe release kinetics or the criticality of timing release (Appeal Br. Appeal 2021-001281 Application 15/850,364 13 2410; see also Breuer Decl. ¶ 20 (“Cottone does not recognize a method of increasing the patency of an acellular vascular graft with a controlled initial inflammation requiring recruitment of host monocytes within one week of graft implantation.”)). For the foregoing reasons, we are not persuaded by Appellant’s contention that Examiner failed “to consider the evidence of record establishing the criticality of incorporating onto the grafts an effective amount of MCP-1 and structuring the graft for timely release of MCP-1 to recruit an effective amount of monocytes for controlled inflammation at the graft site” (Appeal Br. 28; see also Reply Br. 6 (Appellant contends that “Examiner’s reasoning reads out the functional limitations from the claims”); Reply Br. 6-9 and 21-22). To the contrary, we find no evidence on this record to support a conclusion that the amount of MCP-1 on the 10 For the reasons discussed herein, we are not persuaded by Appellant’s conflicting assertions that their claimed invention both involves and does not involve blood vessel growth (see Appeal Br. 23 (Appellant contends that “[o]ne skilled in the art would have no way to translate . . . [Mandrusov’s disclosure of the amount of MCP-1 necessary to, inter alia, induce angiogenesis] to that which applicant claims, which is not blood vessel growth, but control of healing and its alter ego, scarring” and that the combination of Mandrusov, Cottone, and Hunter fails to recognize the criticality of the amount and the timing of MCP-1 release.”) (emphasis added); cf. Reply Br. 10 (Appellant contends that “[t]he combination of the cited art does not recognize the timing for MCP-1 release at the site to initiate early controlled inflammation for a long term graft patency and neotissue formation.”) (emphasis added)). We are also not persuaded by Appellant’s conflicting statements regarding a graft within the scope of Appellant’s claim 11 both requiring and not requiring seeded cells (see November 2, 2021 Oral Hearing Transcript 6:17-19 (Breuer stated that the graft requires seeded cells.); cf. id. at 9:24-10:8 (Brueuer states that the graft does not require seeded cells.)). Appeal 2021-001281 Application 15/850,364 14 biodegradable polymeric vascular graft or conduit made obvious by the combination of Mandrusov, Cottone, and Hunter, which is recognized to attract monocytes, promote angiogenesis, treat restenosis, release active ingredient, and uphold luminal patency, is different than that required by Appellant’s claim 11 (see FF 1-15). We also find no evidence on this record to support a conclusion that those of ordinary skill in this art would not have expected the biodegradable polymeric vascular graft or conduit made obvious by the combination of Mandrusov, Cottone, and Hunter to have the same functionality as the biodegradable polymeric vascular graft or conduit recited in Appellant’s claim 11 (see id.). We find no requirement in Appellant’s claim 11 that limits the placement of MCP-1 to any portion of the biodegradable polymeric vascular graft or conduit. To the contrary, Appellant’s dependent claim 21, reproduced above, expressly limits the scope of the graft or conduit of claim 11 to require that MCP-1 is dispersed throughout the vascular graft or conduit, where independent claim 11 is silent on the matter. Thus, the full scope of Appellant’s claim 11 is not limited to dispersing MCP-1 throughout the vascular graft or conduit. Therefore, we are not persuaded by Appellant’s contention regarding the incorporation of MCP-1, whether formulated as microparticles or not, “throughout the graft, and not just in a portion of the graft” (Appeal Br. 27; see Reply Br. 9 (Appellant contends that its “[c]laim 11, [which] requir[es] an amount of MCP-1 effective to promote neotissue formation at the site of implantation, requires incorporating MCP-1 throughout the graft, including on its surface.”); Appeal Br. 28 (Appellant contends that the combination of Mandrusov, Cottone, and Hunter does “not teach, suggest, or point to incorporating Appeal 2021-001281 Application 15/850,364 15 MCP-1 throughout the graft, nor to the critical timing and amount of MCP-1 for recruiting host monocytes to” a biodegradable polymeric vascular graft or conduit.)). For the foregoing reasons, we are not persuaded by Appellant’s contention that “Mandrusov only mentions that angiogenic substances may be present on the outer surface, without mentioning MCP-1” (Appeal Br. 21; see also Reply Br. 13 (Appellant contends “[a] person of ordinary skill in the art would not incorporate MCP-1 onto Mandrusov’s stents” (emphasis omitted).); cf. FF 2-8, and 13). For the foregoing reasons, we find that the evidence relied upon by Examiner supports a conclusion that the combination of Mandrusov, Cottone, and Hunter makes obvious a biodegradable polymeric vascular graft or conduit within the scope of Appellant’s claim 11. Therefore, we are not persuaded by Appellant’s contention that “[a] person of ordinary skill in the art would not modify Mandrusov’s [biodegradable] stents specifically to make them biodegradable” (see Reply Br. 15 (emphasis omitted); cf. FF 10). For the foregoing reasons, we are not persuaded by Appellant’s contention that the biodegradable polymeric vascular graft or conduit made obvious by the combination of Mandrusov, Cottone, and Hunter does “not have the structure of the grafts required by [Appellant’s] . . . claims” (Appeal Br. 22). Breuer’s statements are made in the context of a rejection that is not before this Panel (see Breuer Decl. ¶ 5 (discussing a rejection over the combination of Cottone and “Cho et al, J. Biomed Mater Res A. 76(2): 252-263 (2006)”)). Therefore, we are not persuaded by Breuer’s statement that “[n]one of the cited references describes an acellular vascular graft that retains the graft site patent by requiring monocyte/macrophage infiltration to allow cellular ingrowth and vascular neotissue formation” Appeal 2021-001281 Application 15/850,364 16 (Breuer Decl. ¶ 6). For the foregoing reasons, we are not persuaded by Appellant’s contention: Because Mandrusov, Hunter, and Cottone do not teach or suggest biodegradable grafts structured to release MCP-1 in an amount effective to recruit host monocytes to the graft within one week of graft implantation and promote neotissue formation at the site of graft implantation, as required by the claims, Mandrusov, Hunter, and Cottone do not make the claimed graft obvious. (Appeal Br. 24.) Hunter discloses that therapeutic agents may be encapsulated into biodegradable microspheres that are coated on a stent (see FF 15). As Examiner emphasizes, Hunter is relied upon “for teaching the technology of making alternative structures of biodegradable implants and not for any specific teaching as to any particular bioactive substance” (Ans. 6). Therefore, we are not persuaded by Appellant’s contentions regarding the therapeutic agents incorporated onto Hunter’s stents or the results obtained by incorporating these substances onto Hunter’s stents or that “Hunter teaches away from recruiting monocytes to its devices” (see Appeal Br. 23- 24 and 28). For the foregoing reasons, we are not persuaded by Appellant’s contentions regarding the functional limitations of Appellant’s claimed invention (see Appeal Br. 25-26). To be clear, the functional and structural requirements of Appellant’s claimed invention have not been ignored (cf. Appeal Br. 26 (Appellant contends that its “evidence on graft structure and function was not considered denying the determination of patentability based on the entire record” (emphasis omitted)); Reply Br. 20). To the contrary, Appellant failed to establish an evidentiary basis to support that the Appeal 2021-001281 Application 15/850,364 17 combination of Mandrusov, Cottone, and Hunter fails to make obvious a biodegradable polymeric vascular graft or conduit within the scope of Appellant’s claimed invention. Mandrusov discloses that its angiogenic substance, MCP-1, can be coated onto its device or deposited into the cavities in a solid form; Cottone discloses that MCP-1 may be incorporated into the matrix of its device; and Hunter discloses that therapeutic substances may be loaded onto biodegradable microspheres (see FF 1-15). Taken together the combination of Mandrusov, Cottone, and Hunter makes obvious the addition of MCP-1, whether formulated into a biodegradable microspheres or not, as a coating, deposited into cavities, or incorporated into the matrix of a biodegradable polymeric vascular graft or conduit (see id.). In addition, the combination of Mandrusov, Cottone, and Hunter makes obvious a biodegradable polymeric vascular graft or conduit that will, inter alia, attract monocytes and cause angiogenesis (see FF 1-15). Therefore, we are not persuaded by Appellant’s contentions regarding the addition of MCP-1, whether formulated as a microparticle or not, into or onto a biodegradable polymeric vascular graft or conduit (see Appeal Br. 27). For the same reasons, we are not persuaded by Appellant’s contention that “[t]he combination of the cited art does not contemplate biodegradable grafts that turn into blood vessels over time” (Reply Br. 9 (citing Appeal Br. 12-17)). For the foregoing reasons, we are not persuaded by Appellant’s contention that its product is functionally and/or structurally different from the product made obvious by the combination of Mandrusov, Cottone, and Hunter (see, e.g., Reply Br. 9). Cottone discloses that a MCP-1 coated biodegradable polymeric vascular graft or conduit, such as that suggested by the combination of Appeal 2021-001281 Application 15/850,364 18 Mandrusov, Cottone, and Hunter may be used to prevent or inhibit restenosis (i.e., “reduce stenosis” as claimed) (see FF 11 and 14). Therefore, we are not persuaded by Appellant’s contention that “[t]he combination of the cited art does not recognize that excessive MCP-1 released at a site leads to excessive inflammation and stenosis” (Reply Br. 9-10); see also id. at 11 (Appellant contends “The Person of Ordinary Skill in the Art would not select MCP-1 to add to Mandrusov’s stents with any reasonable expectation of forming a graft eliciting less stenosis than the Prior Art grafts” (emphasis omitted))). For the foregoing reasons, we are not persuaded by Appellant’s contention that “[t]here is no objective reason why One Skilled in the Art would select from and modify to optimize Mandrusov in view of Hunter and Cottone to arrive at the claimed graft” (Reply Br. 10 (emphasis omitted)). For the foregoing reasons, we are not persuaded by Appellant’s contention that, “[b]ecause the cited art collectively does not guide an artisan of ordinary skill towards the claimed graft [and] does not indicate which parameters are critical for grafts to turn into blood vessels over time without stenosis, the cited art does not make the claimed subject matter obvious” (Reply Br. 11; cf. FF 1-15). For the foregoing reasons, we are not persuaded by Appellant’s contentions regarding improper hindsight or that “[a] person of ordinary skill in the art would not optimize towards the claimed graft as the claimed graft is not contemplated by the cited art” (Reply Br. 12 (emphasis omitted)). Mandrusov does not require that its stent comprises an outer surface having anti-inflammatory agents, anti-migratory substances, inhibitors of matrix synthesis, and combinations thereof (see e.g., FF 6 and 7). Therefore, Appeal 2021-001281 Application 15/850,364 19 we are not persuaded by Appellant’s contention that because Mandrusov discloses biodegradable stents that may comprise: therapeutic agents on the outer surface of the stents contacting a vessel wall particularly include, among others, antiinflammatory agents, anti-migratory substances, inhibitors of matrix synthesis, and combinations thereof[,] . . . one of ordinary skill in the art [would understand] that Mandrusov wants to avoid inflammatory reactions, cell migration towards, and matrix synthesis at the site of its stent’s implantation. (Appeal Br. 21.) See In re Lamberti, 545 F.2d 747, 750 (CCPA 1976) (explaining that a prior art disclosure is not limited only to its preferred embodiments, but is available for all that it discloses and suggests to one of ordinary skill in the art); see also In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971) (Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments.). For the same reasons, we are not persuaded by Appellant’s contentions regarding an alternative embodiment in Mandrusov’s disclosure (see Appeal Br. 22 (citing Mandrusov ¶ 53) (Appellant contends that “[a]s would be apparent to those of ordinary skill in the art, Mandrusov in paragraph [0053] avoids cell infiltration and matrix synthesis at the site of stent implantation.”)). For the foregoing reasons, we are not persuaded by Appellant’s contention regarding “unexpected results” (Appeal Br. 28). Simply stated, Appellant’s contentions are not commensurate in scope with the requirements of Appellant’s claim 11 (cf. Appeal Br. 26-27 (citing Breuer Decl. ¶¶ 15-18 (including the evidence cited therein) (Appellant contends that “limited release of MCP-1 for a short period of time after implantation is important for enhancing neovascular formation to replace the graft Appeal 2021-001281 Application 15/850,364 20 without inducing stenosis, thus leading to more patent vessels.”); Appeal Br. 28 (Appellant contends that the Breuer “Declaration discusses the mechanisms of action of the claimed technology, the criticality of the timing and the amount of MCP-1 release.”)). In addition, although Appellant’s claim 11 does not recite a specific amount of MCP-1, Appellant contends that the Breuer “Declaration shows . . . at least one effective amount for MCP-1 required for host monocyte recruitment in an amount effective to initiate neotissue formation without stenosis. This was about 200 ng of MCP-1 released from a graft implanted in a mouse model” (Reply Br. 20; see also Spec. 33 (Appellant discloses a product releasing “approximately 200ng of MCP-1 from the scaffold over the course of 72 hours.”)). Thus, although Appellant’s disclosure and declaration address one specific amount of MCP-1, claim 11 is open to the use of any amount that may be determined through routine experimentation, i.e. optimization, which achieves the intended result. Appellant’s contentions, therefore, are not commensurate in scope with Appellant’s claimed invention. See In re Huai-Hung Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011) (In order to be persuasive of non-obviousness, “[e]vidence of secondary considerations must be reasonably commensurate with the scope of the claims.”). We recognize Breuer’s reliance on “studies by Roh (Roh et al., PNAS, 107(10):4669-4674 (2010), ‘Roh’, . . .), and Hibino (Hibino et al., FASEB, 25:2731-2739 (201), ‘Hibino 2011a’, . . .)” to “present evidence showing [tissue engineered vascular grafts (TEVGs)] . . . seeded with bone marrow mononuclear cells (BMCs), or unseeded TEVGs secreting MCP-1, undergo inflammation-mediated vascular development driven by recruited host Appeal 2021-001281 Application 15/850,364 21 monocytes” (Breuer Decl. ¶ 9). Initially, we note that neither Appellant’s claims nor the evidence relied upon by Examiner require grafts seeded with cells of any type, thus grafts seeded with BMCs are neither commensurate in scope with the claimed invention or a comparison that could have been construed as relating to the closest prior art on this record (cf. Breuer Decl. ¶¶ 9, 12, 16, 20, 22, 23, and 26 (Breuer discusses published results obtained with grafts seeded with cells.)). See In re Huai-Hung Kao, 639 F.3d at 1068; see also In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art.”). The evidence relied upon by Examiner supports a finding that a biodegradable polymeric vascular graft or conduit comprising MCP-1 will, inter alia, induce graft patency and promote neotissue formation, i.e. angiogenesis (as disclosed by Mandrusov) and blood vessel remodeling (as disclosed by Cottone) (see FF 1-14). Thus, Breuer’s statements regarding the discovery of the precise mechanism by which the prior art achieves its results is not persuasive of non-obviousness (see Breuer Decl. ¶ 13 (Breuer states that “Roh and Hibino 2011a show that it is not the circulating progenitor endothelial cells, as required by Cottone, that induce graft patency, but the recruited host monocytes that infiltrate the graft within one week of implantation and increase the cellularity of the graft to produce a long-term patent neovessel.”)). See, e.g., In re Swinehart, 439 F.2d at 212- 13 (“[I]t is elementary that the mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not cause a claim drawn to those things to distinguish over the prior art.”). Appeal 2021-001281 Application 15/850,364 22 We acknowledge Breuer’s statement that “[m]y studies show that monocytes/macrophages are needed for graft patency, and they are needed at the right time and in the right amount to keep the grafts patent and to induce cellularization of the grafts and neovessel formation” (Breuer Decl. ¶ 14; see also id. ¶ 15 (Breuer states that “Hibino and colleagues (Hibino et al., FASEB, 25:4253-4263 (2011), ‘Hibino 2011b’, . . . show that in a mouse model of vascular neotissue formation from TEVGs the timing and amount of host macrophage infiltration is critical for keeping the TEVGs patent.”)). The evidence on this record, however, supports a conclusion that Breuer’s studies and Hibino 2011b do no more than confirm the results obtained by Mandrusov and Cottone, as well as support a conclusion that those of ordinary skill in this art would have reasonably expected that the biodegradable polymeric vascular graft or conduit, made obvious by the combination of Mandrusov, Cottone, and Hunter would function in the same manner as Appellant’s claimed biodegradable polymeric vascular graft or conduit (see FF 1-15; cf. Breuer Decl. ¶ 25 (Breuer states that “[m]y studies . . . show that a critical cell population, host monocytes/macrophages, is required to be recruited to the graft in an effective amount and at the right time to initiate cellularlization and neovessel formation from the vessel regions neighboring the implanted graft.”)). Appellant’s invention is drawn to a product. Therefore, we are not persuaded by Breuer’s statement that “[t]he claimed method resolves [a] . . . long-standing but unmet need by providing an innovative method of implanting an acellular vascular graft in a patient and keeping the graft patent while it remodels into neotissue” (Breuer Decl. ¶ 24). In addition, we find no requirement in Appellant’s claim 11 that the recited biodegradable Appeal 2021-001281 Application 15/850,364 23 polymeric vascular graft or conduit, if implanted, must “remain[] unoccluded” or “grow with the patient” (cf. id.). Claim 13: Appellant’s claim 13, reproduced above, depends from and further limits Appellant’s claim 11 to require that the biodegradable or bioabsorbable polymers are selected from a group consisting of, inter alia, poly(lactic acid), poly(glycolic acid), polyanhydrides, poly(ortho)esters, polyesters, polyurethanes, poly(caprolactone), or combinations, blends or co-polymers thereof. As discussed above, Mandrusov discloses a biodegradable stent, having a coating comprising MCP-1 on both the inner and outer surfaces of the stent, that is useful in the formation of new blood vessels through angiogenesis, i.e., promotes neotissue formation, induces monocyte homing, and further discloses that amount of MCP-1 required to produce the results disclosed by Mandrusov can be readily determined by those of ordinary skill in this art (see FF 1-9). In addition, Mandrusov discloses that its “stent can . . . be made from bioabsorbable . . . or biostable polymers,” wherein “[r]epresentative examples of polymers that can be used with the embodiments of . . . [Mandrusov’s disclosure] include . . . poly(L-lactic acid); polycaprolactone; . . . polyorthoester; polyanhydride; poly(glycolic acid); . . . [and] polyurethanes” (FF 10). Cottone discloses that such MCP-1 coated biodegradable stents are effective in reducing restenosis and discloses that biodegradable synthetic materials within the scope of its disclosure include “polylactic acid, polyglycolic acid or copolymers and or combinations thereof” (see FF 11-14). Thus, the combination of Appeal 2021-001281 Application 15/850,364 24 Mandrusov, Cottone, and Hunter makes obvious a biodegradable polymeric vascular graft or conduit within the scope of Appellant’s claim 13. For the foregoing reasons, we are not persuaded by Appellant’s contentions regarding “non-biodegradable stents made of a metal or an alloy,” the placement of an implant within a patient, or that “nowhere[] does Mandrusov teach or suggest the biodegradable polymers of claim[] 13[], nor that its stent is degraded to be replaced with neotissue and at the site of graft implantation” (Appeal Br. 29; see also id. at 30 (Appellant contends that “Hunter and Cottone do not provide any reason to choose biodegradable over non-biodegradable devices.”)). For the foregoing reason, we are not persuaded by Appellant’s contention that “[a]bsent Appellant’s disclosure, there is simply no reason why one of ordinary skill in the art would modify Mandrusov’s stents and specifically select the biodegradable polymers of claim 13 from Hunter and Cottone” (id. at 31). Claim 21: Appellant’s claim 21, reproduced above, depends from and further limits Appellant’s claim 11 to require that the MCP-1 is dispersed throughout the vascular graft or conduit. Mandrusov discloses that its angiogenic substance, MCP-1, can be coated onto its device or deposited into the cavities in a solid form; Cottone discloses that MCP-1 may be incorporated into the matrix of its device; and Hunter discloses that therapeutic substances may be loaded onto biodegradable microspheres (see FF 1-15). Taken together, the combination of Mandrusov, Cottone, and Hunter makes obvious the dispersion of MCP-1, whether formulated into a biodegradable microspheres or not, Appeal 2021-001281 Application 15/850,364 25 throughout the biodegradable polymeric vascular graft or conduit, as a coating, deposited into cavities, or incorporated into the matrix of a biodegradable (see id.). Therefore, we are not persuaded by Appellant’s contention that “the prior art provides no objective reason to modify Mandrusov in view of Hunter and Cottone to make Mandrusov’s stents to contain MCP-1 throughout the stent, including on its outer surface” (Appeal Br. 31). For the reasons discussed above, we are not persuaded by Appellant’s contentions regarding an alternative embodiment in Mandrusov’s disclosure (see Appeal Br. 31-32 (citing Mandrusov ¶ 53) (Appellant contends that “Mandrusov avoids inflammation, migration of cells to, and matrix synthesis at the site of implantation.”)). For the reasons discussed above, we are not persuaded by Appellant’s contention that the biodegradable polymeric vascular graft or conduit made obvious by the combination of Mandrusov, Cottone, and Hunter would be “structurally and functionally different from the claimed grafts by avoiding substances with MCP-1 effect on the stent’s outer surfaces” (Appeal Br. 32). Appellant contends: Evidence of record presented . . . shows that cell migration to the graft, inflammation mediated remodeling, and matrix synthesis are required for neotissue formation at the site of graft implantation . . . and replacement of the graft with a neovessel . . . while keeping the graft patent . . . is achieved by incorporating an effective amount of MCP-1 throughout the graft. (id. (citing Breuer Decl. ¶¶ 8-13).) Stated differently, the functionality achieved by Appellant’s claimed invention is a result of incorporating an effective amount of MCP-1 throughout the graft, which as discussed above, Appeal 2021-001281 Application 15/850,364 26 is made obvious by the combination of Mandrusov, Cottone, and Hunter (see FF 1-15). As discussed above, Examiner relies on Hunter to “teach[] the technology of making alternative structures of biodegradable implants and not for any specific teaching as to any particular bioactive substance” (Ans. 6). Therefore, we are not persuaded by Appellant’s contention that “Hunter’s implants contain agents inhibiting MCP-1 production by microphages . . ., including MCP-1 antagonists” (Appeal Br. 33). Cottone discloses “[a] medical device for implantation into vessels or luminal structures within the body . . . , which stimulates positive blood vessel remodeling” (FF 11; see id. (Cottone discloses “a medical device for implanting into the lumen of a blood vessel or an organ with a lumen, which device provides a biocompatible system for the delivery of therapeutic agents locally in a safe and controlled manner[] and . . . thereby stimulating positive blood vessel remodeling,” and a stent for the treatment of restenosis.); FF 14). Cottone further discloses that MCP-1 may be incorporated into the matrix of its device (FF 13). Thus, we are not persuaded by Appellant’s contentions regarding inflammation. For the foregoing reasons, we are not persuaded by Appellant’s contention that: Absent Appellant’s disclosure, there is no objective reason why one of ordinary skill in the art would modify Mandrusov’s stents and select to include MCP-1 onto the stent’s outer surface, since Mandrusov avoids the effects of MCP-1 at the site of stent implantation, Hunter is drawn to MCP-1 inhibitors, and Cottone avoids inflammation. (Appeal Br. 33.) Appeal 2021-001281 Application 15/850,364 27 Claim 23: Appellant’s claim 23, reproduced above, depends from and further limits Appellant’s claim 11 to require that the effective amount of MCP-1 is released from microparticles in the graft over a period of 1 to 3 days after the graft is implanted into the host. As discussed above, the combination of Mandrusov, Cottone, and Hunter makes obvious a biodegradable polymeric vascular graft or conduit, i.e., stent, within the scope of Appellant’s claim 11 that comprises MCP-1 loaded onto biodegradable microspheres that release MCP-1 over time when the stent is implanted into a host (see FF 1-15). As further discussed above, the combination of Mandrusov, Cottone, and Hunter makes obvious the optimization of the rate or duration that a pharmaceutical composition, such as MCP-1 loaded biodegradable microspheres, are released from the stent in order to, inter alia, promote neotissue formation, i.e. angiogenesis, induce monocyte homing, release an active ingredient, such as MCP-1, and uphold luminal patency (see id.). Thus, we are not persuaded by Appellant’s contention that the combination of Mandrusov, Cottone, and Hunter [is] devoid of any teaching or suggestion of a biodegradable vascular device structured to release MCP-1 over a period of 1 to 3 days after the graft is implanted into the host, nor release in an amount effective to recruit an effective amount of host monocytes to the site of graft implantation. (Appeal Br. 34; see also Reply Br. 22-23.) Appeal 2021-001281 Application 15/850,364 28 Claim 27: Appellant’s claim 27, reproduced above, depends from and further limits the graft or conduit of Appellant’s claim 11 to require that the internal diameter of the graft or conduit is larger relative to the internal diameter of the graft or conduit in the absence of MCP-1 ten weeks after implantation of the graft into the host. As discussed above, the combination of Mandrusov, Cottone, and Hunter makes obvious a biodegradable polymeric vascular graft or conduit, i.e., stent, within the scope of Appellant’s claim 11, that comprises an effective amount of MCP-1 to, inter alia, promote neotissue formation, i.e., angiogenesis, induce monocyte homing, release an active ingredient, such as MCP-1, and uphold luminal patency (see FF 1-15). Thus, we find that the stent made obvious by the combination of Mandrusov, Cottone, and Hunter if implanted into a host would necessarily have an internal diameter that is larger relative to the internal diameter of the stent in the absence of MCP-1 ten weeks after implantation of the graft into the host, as required by Appellant’s claim 27. Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. . . . Whether the rejection is based on “inherency” under 35 U.S.C. § 102, on “prima facie obviousness” under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products. In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (footnote omitted). Appeal 2021-001281 Application 15/850,364 29 Therefore, we are not persuaded by Appellant’s contention that “[n]one of the cited art describes their respective devices at ten weeks after implantation, much less compares the structure of their respective devices with and without MCP-1 ten weeks after implantation” (Appeal Br. 35; see also Reply Br. 23-24). CONCLUSION The preponderance of evidence relied upon by Examiner supports a conclusion of obviousness. The rejection of Appellant’s claims 11, 13, 21, 23, and 27 under 35 U.S.C. § 103(a) as unpatentable over the combination of Mandrusov, Cottone, and Hunter is affirmed. Claims 14-17, 30, and 31 are not separately argued and fall with claim 13. Claims 18, 20, 23-26, 29, 32, and 33 are not separately argued and fall with claim 11. Claims 22 are not separately argued and fall with claim 21. Claim 28 is not separately argued and falls with Appellant’s claim 27. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 11, 13-18, 20-33 112(b) Indefiniteness 11, 13-18, 20-33 23, 27, 28 112(d) Improper Dependency 23, 27, 28 11, 13-18, 20-33 103 Mandrusov, Cottone, Hunter 11, 13-18, 20-33 Overall Outcome 11, 13-18, 20-33 Appeal 2021-001281 Application 15/850,364 30 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R. § 1.136(a)(1)(iv) (2019). AFFIRMED