Wook Chun et al.Download PDFPatent Trials and Appeals BoardAug 10, 202013392596 - (D) (P.T.A.B. Aug. 10, 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. 13/392,596 04/13/2012 Wook Chun HI-2 US (044284.0003) 1387 27104 7590 08/10/2020 FENNEMORE CRAIG, P.C. 1700 Lincoln Street Suite 2400 DENVER, CO 80203 EXAMINER MCNEIL, STEPHANIE A N ART UNIT PAPER NUMBER 1653 MAIL DATE DELIVERY MODE 08/10/2020 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte WOOK CHUN, WEON IK CHOI, MAN SEONG PARK, GEUN HYUNG KIM, and JAE DEUK JUNG ____________ Appeal 2019-006119 Application 13/392,596 Technology Center 1600 ____________ Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and MICHAEL A. VALEK, Administrative Patent Judges. VALEK, Administrative Patent Judge. DECISION ON APPEAL Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving claims to a method for preparing a cryopreserved acellular dermal matrix. 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 Industry Academic Cooperation Foundation of Hallym University of Gangwon-do, Korea as the real party in interest. Appeal Br. 2. Herein, we refer to the Final Action mailed October 11, 2018 (“Final Act.”); Appellant’s Appeal Brief filed March 7, 2019 (“Appeal Br.”); Examiner’s Answer mailed June 24, 2019 (“Ans.”); and Appellant’s Reply Brief filed August 14, 2019 (“Reply Br.”). Appeal 2019-006119 Application 13/392,596 2 STATEMENT OF THE CASE The Specification explains: The present invention relates to a method for preparing a cryopreserved acellular dermal matrix and a cryopreserved acellular dermal matrix prepared therefrom. More specifically, the present invention relates to a method in which a cryoprotectant is prepared by adding sucrose to basic constituents comprising glycerol and a basic solution, and then the resulting solution is used to subject skin tissue in which epidermis and cells in dermis are removed to a cryopreservation process and a cryopreserved acellular dermal matrix prepared therefrom. Spec. ¶ 1. According to the Specification, the method it describes “can efficiently increase stability of tissue and maintain extracellular matrix structure without impairment as compared with the conventional methods, when skin tissue for transplantation is processed.” Id. ¶ 5. Claims 1 and 3–7 are on appeal and can be found in the Claims Appendix of the Appeal Brief. See Appeal Br. 5–15. Claims 1 is the only independent claim and illustrative of the claims on appeal. It reads as follows: 1. A method for preparing a cryopreserved acellular dermal matrix consisting essentially of: i) removing epidermis of an isolated allogeneic skin; ii) removing cells in dermis of the epidermis-removed skin; iii) mixing glycerol, sucrose and a basic solution selected from a buffer solution and an animal cell culture medium to obtain a cryoprotectant which consists essentially of the glycerol, the sucrose and the basic solution, wherein the mixing ration of glycerol and the basic solution is 0.8-2 : 9 based on weight, and the sucrose has a concentration of 25% to 40% by weight; Appeal 2019-006119 Application 13/392,596 3 iv) penetrating the cryoprotectant into the skin from which epidermis and cells in dermis are removed, for a penetration interval ranging from 6 to 24 hours; and v) freezing the cryoprotectant-penetrated skin in a controlled rate freezer at a freezing rate of from -0.1 to -5°C per minute to obtain a cryopreserved acellular dermal matrix. Id. at 16. Appellant seeks review of the following rejections: I. Claims 1, 3, and 5 under 35 U.S.C. § 103 as unpatentable over Livesey,2 in view of Taylor,3 Mansbridge,4 and Brockbank;5 II. Claims 4, 6, and 7 under 35 U.S.C. § 103 as unpatentable over Livesey in view of Taylor, Mansbridge, Brockbank, and Wang;6 III. Claims 1 and 3–7 for obviousness-type double patenting (“ODP”) over claims 1–5 of the U.S. Patent No. 9,623,149 (“the ’149 patent”); and IV. Claims 1 and 3–7 as provisionally rejected for ODP over claims 1, 3, and 5–7 of U.S. Patent Application No. 13/386,111 (the “’111 application”) in view of Livesey and Mansbridge. 2 US 2006/0210960 A1, published Sept. 21, 2006 (“Livesey”). 3 US 6,492,103 B1, issued Dec. 10, 2002 (“Taylor”). 4 US 6,291,240 B1, issued Sept. 18, 2001 (“Mansbridge”). 5 US 2004/0067480 A1, published April 8, 2004 (“Brockbank”). 6 X. Wang et al., The Cryopreservation of a Tissue Engineered Dermal Replacement by Programmed Freezing, Proceeding of the 2005 IEEE, Eng’g in Medicine and Biology 27th Annual Conf. (2005) (“Wang”). Appeal 2019-006119 Application 13/392,596 4 I. OBVIOUSNESS REJECTIONS Issue Both of Examiner’s obviousness rejections are premised on the same combination of Livesey, Taylor, Mansbridge, and Brockbank as to independent claim 1. Final Act. 6 (rejecting claims 4, 6, and 7 as obvious over these references “as applied to claims 1, 3, and 5 above, and further in view of Wang”). Appellant presents the same arguments for each rejection and does not argue the claims separately. See generally Appeal Br. 5–14. Accordingly, we consider the obviousness rejections together, focusing on claim 1 as representative of the claims on appeal. The issue is whether a preponderance of the evidence supports Examiner’s conclusion that cited prior art renders the method of claim 1 obvious. Analysis Examiner finds that Livesey teaches a method for cryopreserving acellular dermis comprising the steps recited in claim 1. Final Act. 2–3. Regarding claim step iii), Examiner determines that Livesey teaches the use of solutions comprising both “penetrating” cryoprotectants, such as glycerol, and “nonpenetrating” cryoprotectants, such as sucrose. Id. at 3. Examiner acknowledges that “Livesey does not teach the claimed ratios of ingredients in the c[ry]oprotectant solution,” but determines Livesey teaches cryoprotectant solutions “contain[ing] between 6% and 12% sucrose” that also “comprise a mixture of other sugars/nonpenetrating c[ry]oprotectants, and that the total amount of these compounds is up to 46% of the solutions.” Id. (referring to amounts of “dextran, raffinose, PVP, trehalose, and sucrose” in “formulations VS2 – VS4” in Livesey ¶¶ 88–90, 145). Examiner further determines that Taylor teaches a cryoprotectant solution containing a range Appeal 2019-006119 Application 13/392,596 5 of sucrose (i.e., “1% to 30%”) and Mansbridge teaches a cryoprotectant solution containing a range of glycerol (i.e., “5-10%) that, when combined, overlap with the ranges recited in claim 1. Id. at 3–4. Based on these teachings, Examiner concludes it would have been obvious to apply “Mansbridge’s and Taylor’s guidance on amounts of glycerol and sucrose to include in Livesey’s c[ry]oprotectant solution” because “Mansbridge and Taylor teach[] details of levels of cryoprotectants that Livesey teaches are useful in [its] method” and “Livesey teaches that several nonpenetrating compounds, including sucrose, have the same functions, and therefore they are obvious to substitute for each other.” Id. at 4. Examiner further concludes that it would have been obvious to combine Brockbank’s teaching regarding the penetration time for a cryoprotectant solution with Livesey’s method. Id. at 4–5. Appellant disputes Examiner’s obviousness rejections in several respects. Among other things, Appellant contends that “Livesey merely recites glycerol and sucrose in a longer list of cryoprotectants” and “[n]othing in Livesey suggests the benefits of combining the respective cryoprotectants when used as is presently claimed.” Appeal Br. 6. In particular, Appellant relies on data in the Specification and Declaration of Weon Ik Choi dated March 19, 2014 (“Choi Declaration”) showing “the benefits of using sucrose in the amounts claimed,” namely that “the [claimed] cryoprotectants containing 25% to 40% by weight of sucrose were exceptionally stable in comparison to” a solution comprising “7% dextran, 6% sucrose and 6% raffinose” as taught in Livesey. Id. at 6–8. Appellant further disputes Examiner’s reliance on the sucrose and glycerol ranges taught in Taylor and Mansbridge respectively, urging that Examiner’s Appeal 2019-006119 Application 13/392,596 6 rationale for combining these references with Livesey is “logically defective” because Examiner has not sufficiently explained why it would be “necessary or desirable to optimize the constituents of [Livesey’s] cryoprotectant solution” according to the ranges taught in those references. For such reasons, Appellant urges that Examiner’s rejection is premised on impermissible “hindsight” and a “mix-and-match approach” that, inter alia, “equates methods of preserving cells [as taught in Taylor and Mansbridge] to a method [of] preserving acellular dermal matrix,” as recited in claim 1. See id. at 9–10, 14. Based on the current record, we determine that Appellant has the better position. Examiner’s obviousness rejections are premised on the conclusion that it would have been obvious for a skilled artisan to select two particular cryoprotectants (i.e., sucrose and glycerol) from the much longer list of cryoprotectants set forth in Livesey, choose to combine them, and then adjust the amounts of those components to the recited ranges. The evidence Examiner cites to support that conclusion are teachings in Taylor and Mansbridge regarding different solutions comprising an array of other ingredients in a wide range of amounts. See, e.g., Taylor 11:54–13:57 (describing various “exemplary” base solutions comprising a multitude of ingredients other than sucrose); Mansbridge 16:60–17:28 (describing solutions comprising an array of ingredients “with or without 5–10% glycerol”). Appellant does not dispute that at least some of the solutions taught in Taylor contain sucrose, and at least some of the solutions taught in Mansbridge contain glycerol, in amounts that overlap to some extent with the ranges recited in claim 1. However, Examiner has not sufficiently explained why it would have been obvious for one of ordinary skill to select Appeal 2019-006119 Application 13/392,596 7 Taylor and Mansbridge’s teachings regarding these ranges from the much broader array of solutions and ingredients described in these references for the purpose of modifying Livesey’s method.7 In addition, we are persuaded by Appellant’s argument that the results in the Choi Declaration demonstrate “unexpectedly good” results for solutions containing “25–40% by weight” sucrose, as recited in claim 1. The Choi Declaration reports “degradability by collagenase”8 data for solutions containing glycerol and phosphate buffered saline in a 1:9 weight ratio with sucrose added in 5% increments from 10–40% by weight. Choi Decl. 2. The data show “considerably increased stability” for solutions “containing 25, 30, 35 and 40% by weight sucrose . . . as compared with those prepared with . . . 10, 15 and 20% by weight of sucrose.” Id. at 4. Moreover, the Choi Declaration compares these results to the “Reagan” solution, i.e., a solution containing “7% dextran, 6% sucrose and 6% raffinose . . . added to a solution in which glycerol and phosphate buffered saline were mixed in the weight ratio of 1 : 9.” Id. at 2. Again, the data show that the Reagan solution has significantly “less stability” than the same 7 We are not persuaded by Appellant’s argument that Taylor, Mansbridge and Brockbank are “non-analogous art” to Livesey. See Appeal Br. 12–13. All of the cited references are concerned with the preservation of biological materials for subsequent transplantation and are, therefore, within the same “field of endeavor.” See Airbus S.A.S. v. Firepass Corp., 941 F.3d 1374, 1379 (Fed. Cir. 2019). 8 “Because the main structural component of the dermis is collagen, the stability of the acellular dermal matrix can be measured by using a collagenase” and then quantifying the amount of “release L-leucine equivalent” with a lower amount of released L-leucine indicating increased stability of the acellular dermal matrix. Choi Decl. 4. Appeal 2019-006119 Application 13/392,596 8 mixture of glycerol and phosphate buffered saline, but containing 25–40% sucrose. Id. at 5. Examiner determines that “the Declaration does not establish unexpected results” because the Reagan solution tested therein is not comparable to the ones taught in Livesey. Ans. 12. We disagree. Examiner’s rejection is primarily based on the method taught in Livesey Example 1. Final Act. 3 (citing Livesey ¶¶ 140–145). The method in that example employs a cryoprotectant solution with the same sugars in the same amount as the Reagan solution, but without glycerol. Livesey ¶ 145. Indeed, Livesey exemplifies several solutions comprising various of the ingredients it lists, but none of those exemplary solutions contain glycerol or an amount of sucrose above 12% by weight. See id. ¶¶ 87–90, 145. Accordingly, the Reagan solution and the 20% sucrose described in the Choi Declaration are actually closer prior art to the cryoprotectant solution recited in claim 1, step iii) than the exemplary solutions taught in Livesey. For this reason, the data in the Choi Declaration showing that samples prepared with the cryoprotectant solution of claim 1 exhibited increased stability over those prepared with the Reagan and 20% sucrose solutions is probative of unexpected results. See MPEP § 716.02(e)(I) (“Applicants may compare the claimed invention with prior art that is more closely related to the invention than the prior art relied upon by the examiner.”). To the extent Examiner discounted the Choi Declaration because it did not compare the claimed invention to a solution based on “Livesey’s teachings as a whole, in view of the secondary references,” i.e., a solution with the same ingredients in the same amounts as those in the claim based on Examiner’s combination of the references (see Ans. 12), that was in error because that “would amount to Appeal 2019-006119 Application 13/392,596 9 requiring comparison of the results of the invention with the results of the invention.” In re Chapman, 357 F.2d 418, 422 (CCPA 1966); see also MPEP § 716.02(e)(III) (“Although evidence of unexpected results must compare the claimed invention with the closest prior art, applicant is not required to compare the claimed invention with subject matter that does not exist in the prior art.”). For these reasons, we determine that Examiner’s rejection of claim 1 as obvious over the cited prior art is not supported by the preponderance of the evidence and, therefore, reverse. We reverse the obviousness rejections of claims 3–7 for the same reasons. II. ODP REJECTION OVER CLAIMS OF THE ’149 PATENT The issue for this rejection is whether the preponderance of evidence of record supports Examiner’s conclusion that claims 1 and 3–7 are obvious over claims 1–5 of the ’149 patent. Appellant does not argue any claim separately. We select claim 1 as representative for our analysis; the other claims stand or fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(iv). Examiner’s ODP rejection is substantially based on claim 1 of the ’149 patent, which teaches as follows: 1. A method for preparing an acellular dermal matrix comprising the steps of: i) removing epidermis of an isolated allogenic skin; ii) removing cells in dermis of the epidermis-removed skin; iii) mixing a cryoprotectant to include glycerol, propylene glycol, sucrose and a basic solvent or solution, wherein the mixing ratio of glycerol, propylene glycol and the basic solvent or solution is 0.8-1.5:0.8-1.5:7-9 based on weight, and the cryoprotectant contains sucrose in an amount ranging from 25% to 40% by weight of the cryoprotectant; Appeal 2019-006119 Application 13/392,596 10 iv) penetrating the cryoprotectant into the skin from which epidermis and cells in the dermis are removed; and v) freeze-drying the cryoprotectant-penetrated skin at a freezing rate of from –0.1 to –5° C. per minute to obtain an acellular dermal matrix. ’149 patent 8:30–46. Examiner finds “[c]laim 1 of the instant application is identical in scope to claim 1 of patent ‘149, with the exception of step (iii)” because claim 1 of the ’149 patent teaches that the cryoprotectant in its method includes propylene glycol in addition to the other ingredients recited in Appellant’s present claim 1. Final Act. 10. Examiner determines that propylene glycol is not excluded by the “consisting essentially of” transition phrase in present claim 1 and, therefore, the claims of the ’149 patent “recite all the limitations of the instant claims.” Ans. 16. We determine that Examiner’s ODP rejection is supported by the preponderance of the evidence. We agree with and adopt Examiner’s findings and conclusion of obviousness, as articulated by Examiner. See Final Act. 10; Ans. 8–9, 16. As explained below, Appellant’s arguments to the contrary are not persuasive. Appellant argues that the claims of the ’149 patent are distinguishable from present claim 1 in two respects: (1) the patented claims’ use of propylene glycol in addition to the sucrose, glycerol and a basic solution in the cryoprotectant of step iii) of present claim 1; and (2) the claims of the ’149 patent teach that the “cryoprotectant-penetrated skin is freeze dried,” whereas the last step of present claim 1 recites that it is frozen in “a controlled rate freezer.” See Appeal Br. 14–15. Appeal 2019-006119 Application 13/392,596 11 With respect to Appellant’s first argument, we are unpersuaded because Appellant has not demonstrated that propylene glycol is excluded by the “consisting essentially of” transition phrase in claim 1. “If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of ‘consisting essentially of,’ applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of applicant’s invention.” MPEP § 2111.03(III). The Specification indicates that the basic and novel feature of the invention is an improvement to “the stability of tissue of the cryopreserved acellular dermal matrix,” resulting, at least in part, from the addition of sucrose in the recited amount to the cryoprotectant solution. Spec. ¶¶ 5, 11. Appellant does not dispute that the Specification identifies improved tissue stability as the basic and novel feature of the claimed method. See Reply Br. 2 (“Essentially, practicing what is claimed has the benefit of improved structure in the acellular dermal matrix and results in less damage to the matrix thereof.”). However, Appellant has not met its burden to show that the addition of propylene glycol to that solution, as taught in claim 1 of the ’149 patent, would materially change that feature. Indeed, Appellant fails to point to any evidence of such in its Appeal Brief. See Appeal Br. 14–15. If anything, the ’149 patent evidences that the use of propylene glycol, in addition to ingredients recited in present claim 1, does not materially affect the increased stability observed from the addition of sucrose in the recited amounts. Figure 4 of the ’149 patent shows increased stability for a cryoprotectant solution containing glycerol, propylene glycol, buffer and 30% by weight sucrose relative to certain comparative examples in an assay Appeal 2019-006119 Application 13/392,596 12 similar to the one described in the Choi Declaration. ’149 patent, 8:13–18, Fig. 4. Moreover, based on the “Histological Examination” in Experimental Example 1, the ’149 patent concludes that “it can be known that in the acellular dermal matrix treated with a cryoprotectant containing 20% by weight or more of sucrose [in a solution containing glycerol, propylene glycol, and phosphate-buffered saline in a 1:1:8 ratio] the destruction of tissue that occurred in the course of freeze-drying is remarkably reduced” and has “much better stability of tissue” as compared to samples frozen with solutions containing no or less sucrose. Id. at 7:30–57. For these reasons, we interpret the “consisting essentially of” transition phrase in present claim 1 such that it does not exclude the presence of propylene glycol as recited in claims 1–5 of the ’149 patent. Accordingly, Appellant’s present claims are not distinguished from the claims of the ’149 patent on this basis. We are similarly unpersuaded by Appellant’s argument regarding the freezing step of present claim 1. As Examiner points out, the claims of the ’149 patent recite the same “active step of freezing, at the same rate as the instant claims.” Ans. 16; compare ’149 patent claim 5, with present claim 7 (both reciting a “freezing rate of -1°C per minute”). Appellant’s argument that freezing and freeze-drying “affect the skin tissue in very different ways and require different protocols” is unsupported attorney argument and, therefore, unpersuasive. See In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984) (explaining that arguments and conclusions unsupported by factual evidence carry no evidentiary weight). For these reasons, we agree with Examiner the freezing step of Appellant’s present claims would have been obvious over the teachings in claims 1–5 of the ’149 patent. Appeal 2019-006119 Application 13/392,596 13 For all these reasons, we affirm the rejection. III. PROVISIONAL ODP REJECTION The issue for this rejection is whether the preponderance of evidence of record supports Examiner’s conclusion that claims 1 and 3–7 are obvious over claims 1, 3, and 5–7 of the ’111 application in view of Livesey and Mansbridge. As before, Appellant does not argue any claim separately. We select claim 1 as representative for our analysis; the other claims stand or fall with claim 1. See 37 C.F.R. § 41.37(c)(iv). Examiner determines that claim 1 of the ’111 application “encompasses all the limitations [of the claims] of the instant application except for the steps of removing the epidermis and the inclusion of glycerol” in the cryoprotectant of step iii). Final Act. 11. Examiner finds that these steps are taught by Livesey and that Mansbridge would additionally motivate one of ordinary skill in the art to include glycerol in the cryoprotectant solution. See id. at 11–12. Appellant does not specifically dispute these findings, nor Examiner’s conclusion of obviousness based on them, in its Appeal Brief. 9 Instead, Appellant merely asserts that [t]his rejection is provisional in nature, and so it should have no bearing upon this appeal. The inclusion of Mansbridge is, however, made in error because following Mansbridge leads 9 We note that only those arguments timely presented in the Appeal Brief have been considered; arguments not so presented are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any bases for asserting error, whether factual or legal, that are not raised in the principal brief are waived.”). Appeal 2019-006119 Application 13/392,596 14 also to the use of DMSO in the cryoprotectant as discussed supra. Mansbridge is nonanalogous art as explained supra. Appeal Br. 15. These arguments are unpersuasive. Appellant’s DMSO argument is not clearly presented in the Appeal Brief. As we understand it, Appellant contends Mansbridge teaches that DMSO should be included in the cryoprotectant (in addition to the ingredients recited in claim 1), but that the “consisting essentially of” transition phrase excludes DMSO and, therefore, claim 1 would not be obvious over the articulated combination of the ’111 application claims with Livesey and Mansbridge. We are not persuaded because, even if the articulated combination of references would lead to the inclusion of DMSO, Appellant has not shown that DMSO “would materially change the characteristics of applicant’s invention.” See MPEP § 2111.03(III). The only evidence Appellant cites for such a proposition is Example 2 and Figures 15 and 16 of Taylor. Appeal Br. 11. According to Appellant, this example and the results in the figures show that “[c]ell viability is enhanced” by the addition of “0.5% to 3% DMSO” to the cryoprotectant media taught in Taylor. Id. However, Appellant has not explained how such evidence demonstrates a material change to the basic and novel properties of claim 1, i.e., improved stability of tissue of the cryopreserved acellular dermal matrix. Thus, Appellant has not sufficiently shown that the addition of DMSO is excluded by the “consisting essentially of” transition phrase in present claim 1. We are likewise unpersuaded by Appellant’s non-analogous art argument. Mansbridge, Livesey, and the claims of the ’111 application all describe methods for preserving biological materials for subsequent Appeal 2019-006119 Application 13/392,596 15 transplantation and, therefore, are within the “same field of endeavor” as the present claims. See Airbus, 941 F.3d at 1380. Accordingly, Mansbridge is analogous art. For these reasons, we affirm the provisional ODP rejection. CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 3, 5 103 Livesey, Taylor, Mansbridge, Brockbank 1, 3, 5 4, 6, 7 103 Livesey, Taylor, Mansbridge, Brockbank, Wang 4, 6, 7 1, 3–7 Obviousness-type Double Patenting 1, 3–7 1, 3–7 Provisional Obviousness-type Double Patenting 1, 3–7 Overall Outcome 1, 3–7 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). AFFIRMED Copy with citationCopy as parenthetical citation