DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/27/2026 has been entered.
Claim Status
As of the Final Office Action mailed 6/1/2026, claims 1-4, 9, and 11-15 were pending and claim 12 was withdrawn for being drawn to nonelected invention.
In Applicant's Response filed on 8/27/2026, claims 1-4 were amended and claims 9 and 13-15 were canceled.
As such, claims 1-4 and 11-12 are pending and claims 1-4 and 11 have been examined herein.
Withdrawn Objections/Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The objection of record to claim 2 for minor informalities has been withdrawn in view of Applicant’s amendment to claim 2.
The rejection of record of claims 1-4, 9, 11, and 13-15 under 35 USC § 112(b) have been withdrawn in view of Applicant’s amendment to claim 1. The rejection of claims 9 and 13-15 are moot in view of their cancelation.
The rejection of record of claims 9 and 13-15 under 35 USC § 102(a)(1) and (a)(2) as being anticipated by Ozbolat et al (US 20190331662 A1, 1/12/2018; published 10/31/2019; of record) is moot in view of the cancelation of these claims.
The rejection of record of claims 1-4, 9, 11, and 13-15 under 35 USC § 103 as being unpatentable over Badylak et al (WO2015143310 A1, 3/20/2015; published 9/21/2016; of record) in view of Hines et al (Cell Reports, 13 March 2014; of record) have been withdrawn in view of Applicant’s arguments.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-3 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Badylak et al (WO2015143310 A1, 3/20/2015; published 9/21/2016; of record) in view of Fong et al et al (Tissue Eng Part A. 2016 Aug;22(15-16):1016-25).
Regarding claims 1-4 and 11, Badylak teaches a method of preparing an extracellular matrix-derived gel comprising: (i) solubilizing extracellular matrix (ECM) that has not been dialyzed, by digestion with an acid protease in an acidic solution to produce a digest solution, (ii) drying the digest solution, and (iii) sterilizing the dried digest (see claim 1 of Badylak).
Badylak continues to teach that the dried digest solution is lyophilized (see claim 5 of Badylak). The ECM is derived from mammalian tissue, wherein the mammalian tissue is derived from pancreas (see claims 7-8 of Badylak). The reference also teaches that all the solutions are maintained below 25 C before gelation (see claim 14 of Badylak). The acidic solution comprises 0.01 M HCl and the protease is trypsin (see claims 18-19 of Badylak). Lyophilized porcine spleen was mixed with pepsin and HCl and kept at a constant stir for 72 hrs and dry human liver was mixed with pepsin and HCl and kept at constant stir for 3-5 days (i.e., 72- 120 hours) (see paras 91 and 95). A base or isotonic solution is added to raise the pH of the digest solution where the solution is raised to between 7.2 and 7.8 (see claims 20 and 34 of Badylak).
Badylak does not teach that the stirring is performed at 330 to 500 rpm.
However, Fong teaches extracellular matrix material produced from cardiac tissue (abstract).
Fong continues to teach that bovine adult and fetal hearts were purchased from Sierra Medical (“Cardiac tissue decellularization and ECM generation” para 1). Before decellularization, the tissue (100–200 g) was processed by removing all excess fat and stored at −80°C for at least 16 h (same para). Next, the tissue was cut into 3 mm3-sized pieces and subjected to continuous stirring at 330 RPM during incubation in the following solutions at room temperature: ddH20 for 30 min, 2× phosphate-buffered saline (PBS) for 15 min, sodium dodecyl sulfate (SDS) (1% for adult tissue and 0.5% for fetal tissue) for 72 h, and 1% Triton for 90 min. This was followed by seven washes in ddH20 for 30 min each, and 18 h in PBS with antibiotic–antimycotic (Life Technologies) at 4°C (same para).
Decellularized tissues were lyophilized and then milled using a cheese grater to create a fine powder (“Cardiac tissue decellularization and ECM generation” para 2). The ECM powder was digested with 2 mg/mL pepsin diluted in 0.01 M cell culture grade hydrochloric acid (HCl) (same para). Approximately 200 mg of cardiac ECM was added to 20 mg of pepsin and continuously stirred at 330 RPM at room temperature for 48–72 h or until fully digested (same para). The digested ECM was divided into 1 mL aliquots and stored at −80°C until needed (same para).
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to produce ECM from pancreatic tissue as taught by Badylak, where the digestion occurs at a speed of 330 rpm as taught by Fong, to arrive at the instantly claimed invention. Fong shows that tissue can be successfully decellularized and digested at a speed of 330 rpm for 72 hours. One of ordinary skill would have been motivated to modify the method of Badylak to include stirring at 330 rpm as taught by Fong with a reasonable expectation of advantageously producing ECM material for cell culture as taught by the prior art. It was prima facie obvious, prior to the effective filing date, that a stirring speed of 330 rpm was effective for methods of producing ECM from decellularized tissue.
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive. Applicant’s arguments with respect to the Hines reference have been considered but are moot because the new ground of rejection does not rely on the reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Badylak and Fong as applied to claims 1-3 and 11 above, and further in view of Saldin et al (Acta Biomater. 2017 Feb;49:1-15. Epub 2016 Dec 1).
The teachings of Badylak and Fong in combination were recited in the above 35 U.S.C. 103 rejection as applied to claim 1 of which claim 4 depends. The teachings will not be repeated here.
Neither Badylak nor Fong teach:
the stirring at 330 rpm occurs for 96 hours.
However, Saldin teaches extracellular matrix hydrogels from decellularized tissue (title).
Saldin continues to teach that ECM hydrogel formation is a collagen-based self-assembly process that is regulated in part by the presence of glycosaminoglycans, proteoglycans, and ECM proteins (“ECM Hydrogel Formation” para 1). Therefore, polymerization kinetics will be influenced by the native biochemical profile of the source tissue and of the proteins that remain after decellularization and solubilization (same para). It is important to achieve sufficient cell removal from source tissues while maintaining ECM composition and ultrastructure. The choice of solubilization protocol is crucial to not adversely affect the ability to subsequently form an ECM hydrogel (same para). Table 1 provides an overview of the many methods used to decellularize source tissues and solubilize the remaining ECM.
Saldin continues to teach that the most prevalent method used to form an ECM hydrogel is via pepsin mediated solubilization of a comminuted (powder) form of ECM (also called “ECM digestion”) (“ECM Hydrogel Formation” para 2). Pepsin is an enzyme derived from porcine gastric juices that has been used since 1972 to solubilize a substantial portion (up to 99%) of acid-insoluble collagen (same para). Pepsin cleaves the telopeptide bonds of the collagen triple helix structure to unravel collagen fibril aggregates. The ECM material is first powdered and stirred in pepsin with dilute hydrochloric acid over 48 hours, as reported by Freytes et al. and designated herein as the “Freytes method” (same para). Another method involves the use of 0.5 M acetic acid instead of 0.1 M HCl as a base medium for the pepsin enzyme (“Voytik-Harbin method”). Pepsin digestion or solubilization is complete when the liquid is homogenous with no visible particles (same para). Different digestion times will produce a different profile of cryptic molecules, some of which possess bioactive properties, suggesting the preferred digestion period will need to be tailored for each clinical application; times of 24 – 96 hours have been reported (Table 1) (same para). The “solubilized ECM” or “ECM digest” forms a gel when the liquid is neutralized to physiologic pH, salt concentration and temperature in vitro (“ECM hydrogel”) in an entropy-driven process dominated by collagen kinetics.
Therefore, it would have been obvious prior to the effective filing date of the instantly claimed invention to produce ECM from pancreatic tissue by digesting at 330 rpm as taught by Badylak and Fong in combination, where the digestion period is for 96 hours as taught by Saldin, to arrive at the instantly claimed invention. Saldin shows that the digestion time to produce ECM hydrogels can vary between 24 and 96 hours. It would have been a matter of routine experimentation for one of ordinary skill in the art using standard laboratory techniques available at the time of filing to determine that optimal digestion period. One of ordinary skill would modify the digestion time of Badylak and Fong in combination to include 96 hours to tailor the cryptic molecule profile of the ECM for the appropriate clinical application as taught by the prior art.
Conclusion
No claim is allowed.
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/DAVID A MONTANARI/Examiner, Art Unit 1632
/G.R./Examiner, Art Unit 1632
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