DETAILED ACTION Claims 1-20 are under consideration on the merits. Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority Acknowledgment is made of applicant's claim for foreign priority based on an application filed in China on 12/31/2020 . It is noted, however, that applicant has not filed a certified copy of the application as required by 37 CFR 1.55. Information Disclosure Statement The information disclosure statement (IDS) submitted on 6/19/23 was filed prior to the mailing date of a first Action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, it was considered by the Examiner . Claim Objections Claim s 7 and 13-15 are objected to because of the following informalities: In the preamble of each of claims 7 and 13-15, “comprising” should be “comprises” for correct grammar. Correction is required. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.— The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Clai m 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 13 recites “the cross-linked biological material.” There is no clear antecedent basis for this limitation, and base claim 1 recites two different crosslinking steps. Does claim 13 refer to the biological material after the first crosslinking step, the second crosslinking step, or to the biological material after either the first crosslinking or the second crosslinking? Clarification is required. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claims 1-20 are rejected under 35 U.S.C. 103 as unpatentable over Dove et al. (US 2021/0100931). The teachings of Dove are relied upon as discussed above , and Dove teaches the limitations of claims 16-17 as discussed above in the 102 rejection . As to claims 1-20, Dove discloses a bioprosthetic tissue (“biological material”) prepared by pre-treating the tissue with a chemical fixative agent to extensively crosslink the tissue (a “second crosslinking”), wherein the agent may be glutaraldehyde and wherein the glutaraldehyde is capable of crosslinking collagen fibers as recited by claim 1, oxidizing antigenic carbohydrates present in the tissue (“mucopolysaccharides” of claim 1) using an oxidizing agent that converts vicinal diol moieties (“hydroxyl groups” of claim 1 that will include ortho-hydroxyl groups of claim 4) into aldehydes, and further crosslinking (a “first crosslinking”) with lysine (a “first crosslinking agent” of claim 1 that occurs after the oxidation as recited by claim 1 and that is capable of crosslinking aldehyde groups of the mucopolysaccharide and of claims 9-10 having at least two active groups capable of reacting with aldehyde groups and which is different than the other crosslinking agent and which is capable of reacting with active groups on it as recited by claim 8)(paragraphs 9-12, 55, 72-73, 92). The first crosslinking occurs after the oxidation as required by claim 1. Dover further discloses dehydrating the tissue (paragraph 140), which occurs after the oxidation and crosslinking reactions as recited by claim 1. Regarding claim 2, the tissue may be a porcine heart valve (paragraph 110). As to claim 3, the tissue is exposed to a solution comprising the oxidant (paragraph 66). Regarding claim 5, the oxidant may be sodium periodate (paragraph 24). Regarding claim 6, the oxidation is carried out by exposing the tissue to the oxidant solution for from several hours to 24 hours (paragraph 66), which overlaps the claimed range. Dove discloses a specific embodiment wherein sodium periodate is used in the amount of 20 mM, which is about 0.42 wt %, which is within the range of claim 6, and the tissue is exposed to the oxidant solution with shaking (“dynamic contact ”)( paragraph 139). Regarding claim 8, the lysine crosslinking agent taught by Dove as discussed above meets the limitations of claim 8 as having two active groups capable of reacting with aldehyde groups, and the glutaraldehyde crosslinking agent as taught by Dove is different than the lysine first crosslinking agent and is capable of reacting with the active groups of the first crosslinking agent as recited by claim 8. As to claim 19, the valve may be a stented valve (paragraph 110). As to claims 1-20, Dove does not further expressly disclose a specific embodiment of a material prepared by a) oxidation, b) first crosslink8ing, c) second crosslinking, and d) dehydration, wherein b) is performed after a), and a), b) and c) are all performed prior to d . As to claims 1-20, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the biological material of Dove As to claim 7, Dove does not expressly teach the recited sequence of steps, i.e., oxidation followed by first crosslinking followed by the second crosslinking, as opposed to Dover’s disclosure of the second crosslinking being followed by the oxidation and the first crosslinking, which in one embodiment may occur simultaneously (see paragraph 91). As to claim 14, Dove does not expressly teach the sequence of steps recited by the claim, i.e., oxidation followed by second crosslinking followed by the first crosslinking, as opposed to Dove’s disclosure of the second crosslinking being followed by the oxidation and the first crosslinking, which in one embodiment may occur simultaneously (see paragraph 91). As to claim 15, Dove does not expressly teach the sequence of steps recited by claim 15, i.e., oxidation followed by second crosslinking followed by the first crosslinking, as opposed to Dove’s disclosure of the second crosslinking being followed by the oxidation and the first crosslinking, which in one embodiment may occur simultaneously (see paragraph 91). As to claims 7 and 14-15, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the disclosure of Dove by changing the sequence of the oxidation and first and second crosslinkings to arrive at the sequences recited by these claims, because a change in the sequence of adding ingredients in a process claim is prima facie obvious in the absence of new or unexpected results. See Ex parte Rubin , 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans , 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson , 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.). Here, there is no evidence of record of any new and unexpected result as a consequence of the sequence recited by the present claims. Regarding claim s 11 and 16 , Dove further discloses that the lysine crosslinking agent is reacted with the tissue for 1-3 hours, which overlaps the recited range s (paragraph 87), but does not disclose the concentration range of the crosslinking agent as recited by the claim. As to claim s 11 and 16 , it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the disclosure of Dove to arrive at the recited concentration of the lysine crosslinking agent with a reasonable expectation of success because the function of the lysine is the same in both the Dove disclosure and the present invention, i.e., to serve to crosslink a biological material such as a heart valve. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical . “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller , 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Regarding claim s 12 and 17 , Dove further discloses an embodiment wherein the glutaraldehyde is used in the amount of 0.625% at room temperature, which is within the recited concentration and temperature ranges, and for a time period of one hour, which is above the recited time range (paragraph 127), but also discloses an embodiment wherein the time period is 7-14 days, which is within the recited range (paragraph 127). Dove does not expressly disclose a specific embodiment wherein both the temperature during the glutaraldehyde crosslinking reaction and the time period for the crosslinking reaction are within the recited ranges. As to claim s 12 and 17 , it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the disclosure of Dove by selecting a temperature and time period for the glutaraldehyde crosslinking reaction that is within the recited ranges because Dove expressly teaches such temperatures and time periods as suitable for glutaraldehyde crosslinking reactions of biological materials. Such a modification is merely the combining of known prior art elements according to known methods to achieve predictable results, which is prima facie obvious. MPEP 2143. As to claim 13, Dove further discloses that the use of glutaraldehyde as a crosslinker is known to render bioprosthetic tissues more susceptible to calcification due to their high levels of residual aldehyde groups (paragraph 5). Dove does not further expressly teach end capping the crosslinked biological material to block residual active groups from the second crosslinking agent as recited by claim 13. The Office notes that the present specification states that end-capping is performed using a capping substance that may be a polyamino compound such as lysine or hexamethylenediaine (paragraphs 33-36 as published), which are the same compounds that may be used as the first crosslinking agent in the claimed invention (see, e.g., claim 10). As to claim 13, it further would have been prima facie obvious to incorporate an additional step of reacting the crosslinked biological material with lysine a second time after the crosslinking with glutaraldehye in order to eliminate any residual aldehyde groups in light of Dove’s teaching that residual aldehyde groups after glutar a ldehyde crosslinking can be deleterious and promote calcification, and further because the iterative repeating of steps in a method claim is prima facie obvious ( Perfect Web Techs., Inc. v. InfoUSA , Inc. , 587 F.3d 1324 (Fed Cir. 2009) . As to claim 18, Dove does not further expressly teach a post-crosslinking step of exposing the biological material into a third crosslinking solution to crosslink residual active groups from the first crosslinking agent. As to claim 18, it further would have been prima facie obvious to perform an additional crosslinking in order to eliminate any residual groups that could be reactive and therefore deleterious as taught by Dove (paragraph 5) , and further because the iterative repeating of steps in a method claim is prima facie obvious ( Perfect Web Techs., Inc. v. InfoUSA , Inc. , 587 F.3d 1324 (Fed Cir. 2009) . As to claim 20, Dove does not further expressly the maximum breaking force recited by the claim or that the biological material is configured to be crimped and maintained for at least 72 hours and become flattened without creases. The Dove biological material, however, will possess the maximum breaking force recited by the claim and be capable of being crimped and maintained for at least 72 hours and become flattened without creases because it comprises the same biological material formed by the same steps recited by the claims, and a product cannot be separated from its properties. The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the countless ways that an Applicant may present previously unmeasured characteristics. When the prior art appears to contain the same ingredients that are disclosed by Applicants' own specification as suitable for use in the invention, a prima facie case of obviousness has been established, and the burden is properly shifted to Applicants to demonstrate otherwise. See MPEP 2112.01. The Office additionally notes that all pending claims are written in the form of product by process claims. While Dove discloses the process steps recited by the claims as discussed above, the patentability of the claims is ultimately determined by their structure and not by the process steps to produce the product as recited by the claims. “[E] ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by- process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b] ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ( " a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim." ). “The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature” than when a product is claimed in the conventional fashion. In re Fessmann , 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product. In re Marosi , 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983) (The claims were directed to a zeolite manufactured by mixing together various inorganic materials in solution and heating the resultant gel to form a crystalline metal silicate essentially free of alkali metal. The prior art described a process of making a zeolite which, after ion exchange to remove alkali metal, appeared to be “essentially free of alkali metal.” The court upheld the rejection because the applicant had not come forward with any evidence that the prior art was not “essentially free of alkali metal” and therefore a different and unobvious product.). Ex parte Gray, 10 USPQ2d 1922 (Bd. Pat. App. & Inter. 1989) (The prior art disclosed human nerve growth factor (b-NGF) isolated from human placental tissue. The claim was directed to b-NGF produced through genetic engineering techniques. The factor produced seemed to be substantially the same whether isolated from tissue or produced through genetic engineering. While the applicant questioned the purity of the prior art factor, no concrete evidence of an unobvious difference was presented. The Board stated that the dispositive issue is whether the claimed factor exhibits any unexpected properties compared with the factor disclosed by the prior art. The Board further stated that the applicant should have made some comparison between the two factors to establish unexpected properties since the materials appeared to be identical or only slightly different.). Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT GAREN GOTFREDSON whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-3468 . The examiner can normally be reached on FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9AM-6PM . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT David Blanchard can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT 5712720827 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /GAREN GOTFREDSON/ Examiner, Art Unit 1619 /ANNA R FALKOWITZ/ Primary Examiner, Art Unit 1600