DETAILED ACTION
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 .
This rejection is Non-Final due to a new ground of rejection.
Claim Status
Claims 1-9, 11-12, 14, 16-20 and 22 are pending.
Claims 10, 13, 15, and 21 are canceled.
Claims 14 and 16-20 are withdrawn as being directed to a non-elected invention of method, the election having been made on 12/21/2022.
Claims 1-9, 11-12, and 22 have been examined.
Priority
This application claims foreign priority of SINGAPORE 10202003504W filed on 04/16/2020.
Terminal Disclaimer
The terminal disclaimer filed on 9/8/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of application No 17/912,707 has been reviewed and accepted. The terminal disclaimer has been recorded.
Withdrawn Rejection
The rejection of claims 1-9, 11-12, and 22 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn because the amendment to claim 1 overcomes the rejection.
The provisional rejection of claims 1-7 and 22 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, and 10-11 of copending Application No. 17/912,707 is withdrawn because applicant’s filed TD has been approved.
New Ground of Rejection
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.
Claim 22 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being 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 22 is unclear because it is unclear whether claim 22 depends on claim 6 or depends on claim 1, rendering the metes and bounds indefinite.
Maintained Rejection
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.
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.
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.
1. Claims 1-6 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Yan et al. (CN 106075576A, previously cited 1/31/2023) in view of Wang et al. (J Mater Sci: Mater Med (2016) 27:45, previously cited 9/8/2023), and evidenced by Zhu et al. (Biophys J. 2014 Apr 15;106(8):1822-31, previously cited 6/9/2025).
Claim 1 is drawn to a polymeric material comprising
a non-mammalian type I collagen
a crosslinking agent, and
a crosslinked polymer matrix formed from a non-mammalian collagen that has undergone self-crosslinking,
wherein-1, the non-mammalian collagen derived from bullfrog skin has a denaturation temperature that is higher than human body temperature and is derived from bullfrog skin,
Wherein-2, the polymeric material forms a wound dressing,
Wherein-3, the non-mammalian collagen has a fiber diameter of 20 nm to 25 nm, and
wherein-4, either crosslinked polymer matrix is formed without a separate noncollagen
scaffold.
Yan et al. teach a collagen sponge as biomedical materials (p11, Technical field) for promoting wound healing and tissue repair (p11, para 3). Yan et al. teach the collogen is purified from mammalian skin (p13, para 2). Yan et al. teach the polymer material of collagen sponge further comprising carboxymethyl cellulose as a scaffold or filler to prevent the material from collapsing after absorption and provide an expansion support effect (p11, last para/Summary of invention), reading on a polymer for cross-linking to collagen. Yan et al. teach crosslinking the collagen and sodium carboxymethylcellulose to obtain a collagen sponge (p12, para 3-4). Yan et
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al. further teach the crosslinking agent as glutaraldehyde or an epoxy compound crosslinking agent of 1,4- butane Alcohol di(de)hydroglycidyl ether as follows (p12, para 6).
Yan et al. did not teach a collagen as a type I collagen derived from bullfrog skin.
Similarly, Wang et al. teach collagen has wide applications in tissue engineering either on its own, or in combination with other biomaterials as hybrid materials for wound dressings and other common use known in the art (p2, col 1, para 3), consistent with Yan et al. However, Wang et al. teach commercial collagen from bovine or porcine contain infectious agents including bovine spongiform encephalopathy (BSE), transmissible spongiform encephalopathy (TSE) and foot and mouth disease (FMD) (p2, col 1, para 3). Wang et al. further suggest beneficial use of non-mammalian collagen source from bullfrog skin-derived collagen (BFCOL) to replace mammalian collagen and prevent the risk of contaminated infectious agents in biomedical materials (p2, col 1, para 3). Wang et al. teach the collagen purified from bullfrog skin are fibrous type I collagen (p6, col 2, Results 3.1 Characterisation and confirmation of extraction of Type I collagen). Wang et al. further show the denaturation temperature of fibrous type I
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collagen of bullfrog skin-derived collagen (BFCOL) purified by acid solubilization method (p3, col 1, Sec 2.2 Isolation and purification of collagen from fish scales and bullfrog skin) has a skin denaturation temperature that is at about 40ºC and is inherently higher than human body temperature of 37ºC shown above (Supplementary Data, Fig S4), reading on the limitation (i) and wherein-01.
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With respect to the limitation (ii), Yang et al. teach the use of a bi-functional crosslinking agent of 1,4-butanediol glycidyl ether for crosslinking collagen and/or carboxymethylcellulose in a mixture stirred in a homogenizer (reading on blending the mixture).
With respect to the limitation (iii), self-crosslinking is an inherent property of type I collagen as evidenced by Zhu et al. (Biophys J. 2014 Apr 15;106(8):1822-31.) based on turbidity assays shown above (Abstract; p1826, Fig 3).
With respect to the wherein-2, Wang et al. teach collagen has wide applications in tissue engineering either on its own, or in combination with other biomaterials as hybrid materials for wound dressings and other common use known in the art (p2, col 1, para 3),
With respect to the wherein-3, Wang et al. teach the collagen isolated from bullfrog skin is fibrous type I collagen (p6, col 2, 3.1 Characterisation and confirmation of extraction of Type I collagen) purified via acid solubilization method instead of pepsin solubilized treatment to prevent the conversion of collagen into monomeric subunits by pepsin (p2, col 2, para 2), demonstrating Wang’s purified type I collagen of bullfrog is naturally-occurring skin-derived bullfrog collagen. The specification disclosed naturally-occurring skin-derived bullfrog collagen has significant smaller fibre diameter at approximately 20-25 nm [0062]. Applicant further argues that the diameter of an individual fiber as recited in the claim will not change by crosslinking of collagen in the instant Remarks (p7, claim rejection – 35 USC § 112, para 3). Therefore, Wang’s purified naturally-occurring type I collagen from bullfrog inherently has a fiber diameter of 20 nm to 25 nm as claimed.
With respect to the wherein-4, a covalently crosslinked bull frog collagen and carboxymethyl cellulose scaffold via the bi-functional crosslinking agent of glutaraldehyde or an epoxy 1,4- butane Alcohol di(de)hydroglycidyl ether taught by Yan et al. (p12, para 6) is expected to form a stable polymer matrix without a separate noncollagen scaffold by optimizing the amount of polymers and a crosslinking agent.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to replace collagen source of Yan’s cross-linked collagen sponge complex with Wang’s non-mammalian bullfrog skin-derived collagen (BFCOL) because Wang et al. teach commercial collagen from bovine or porcine contain infectious agents including bovine spongiform encephalopathy (BSE), transmissible spongiform encephalopathy (TSE) and foot and mouth disease (FMD) (p2, col 1, para 3) and further suggest beneficial use of non-mammalian collagen source from bullfrog skin-derived collagen (BFCOL) to replace mammalian collagen and prevent the risk of contaminated infectious agents in biomedical materials (p2, col 1, para 3). The combination would have reasonable expectation of success because Wang et al. teach collagen has wide applications in tissue engineering either on its own, or in combination with other biomaterials as hybrid materials for wound dressings and other common use known in the art (p2, col 1, para 3) consistent with Yan et al.
With respect to claims 2-5, Yan et al. teach the crosslinking agent as 1,4-butane Alcohol di(de)hydroglycidyl ether (p12, para 6).
With respect to claim 6, Yan et al. teach the mass ratio of a crosslinking agent may be 0.05% to 5% (p12, para 6).
With respect to claims 11-12, Yan et al. teach a collagen sponge as the polymer material (p11, Technical field).
Applicant’s Arguments
The amendment to claim 1 overcomes the rejection of record because of the following reasons.
Claim 1 as amended recites that the material is formed without a non-collagen scaffold. There is no motivation in Yan to do so, and the skilled person would therefore not have been able to arrive at the material of Claim 1 without using hindsight based on the instant application (Remarks, p9, para 2-4).
Wang et al. is entirely silent on whether a polymeric material which includes a
crosslinked polymer matrix according to Claim 1 would be suitable as a wound dressing (Remarks, p9, last para to p10, para 1).
Response to Arguments
Applicant's arguments filed 9/8/2025 have been fully considered but they are not persuasive for the reasons as follows.
Applicant’s argument (i) is not persuasive because (a) applicant argues a single reference of Yan et al. alone whereas the rejection is based on Yan et al. in view of Wang et al. and Zhu et al., (b) Wang et al. teach beneficial use of non-mammalian collagen source from bullfrog skin-derived collagen (BFCOL) to replace mammalian collagen and prevent the risk of contaminated infectious agents in biomedical materials (p2, col 1, para 3) and (c) all cited references of Yan et al., Wang et al. and Zhu et al. were published several years before the effective filing date of this application; thus, the rejection is based on the combined teachings of cited references not hindsight as argued by applicant. Expected beneficial results are evidence of obviousness. See MPEP 716.02(c).
Applicant’s argument (ii) is not persuasive because Wang et al. teach collagen has wide applications in tissue engineering either on its own, or in combination with other biomaterials as hybrid materials for wound dressings and other common use known in the art (p2, col 1, para 3),
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consistent with Yan et al. The use of collagen sponge has been known by one of ordinary skill in the art for making wound dressing since 1977 as further evidenced by Chvapil (See p722, Table I in J. BIOMED. MATER. RES. VOL. 11, PP. 721-741 (1977)). MPEP 2144 (I) states “The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988).”
Additional Reference
Larsen et al. (US 2011/0021964 A1) teach the use of collagen for wound dressing [0381, 0390] including collagen sponge (claim 6).
2. Claims 1-7, 11-12, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Yan et al. in view of Wang et al. and evidenced by Zhu et al. as applied to claims 1-6, 11-12, 21 and further in view of Chau et al. (Biomaterials 26 (2005) 6518–6529, previously cited 1/31/2023).
Claim 7 is drawn to crosslinked polymer matrix is formed from a non-mammalian collagen that has undergone self-crosslinking by a transglutaminase.
Yan et al. in view of Wang et al. and evidenced by Zhu et al. teach a crosslinked polymer matrix comprising crosslinked type I collagen derived from bullfrog skin with inherent property of self-crosslinking as applied to claims 1-6 and 11-12 described above.
Yan et al. in view of Wang et al. and evidenced by Zhu et al. do not teach the collagen further undergone self-crosslinking by a transglutaminase.
Chau et al. teach “The cellular response to transglutaminase-cross-linked collagen.” (Title). Chau et al. suggest beneficial treatment of native collagen type I with transglutaminase (TG2; tTG) leads to an enhancement in cell attachment, spreading and proliferation of human osteoblasts (HOB) and human foreskin dermal fibroblasts (HFDF) in the abstract. Chau et al. teach transglutaminases catalyze ε(γ-glutamyl)lysine linkage, reading on self-crosslinking of a type I collagen (p6519, col 1, para 1). Because Chau et al. teach the benefits of transglutaminase-mediated cross-linked type I collagen comprising enhanced attachment, spreading and proliferation of cells as well as slowing down collagen degradation leading to improvement of its in vivo efficacy as a biomaterial (p6527, conclusion col 1-2), one of ordinary skill in the art before the effective filing date of this invention would have found it obvious to further treat a type I collage scaffold with transglutaminases to improve the properties of the collagen scaffold, reading on claims 7 and 22.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Yan et al. in view of Wang et al. and evidenced by Zhu et al. with (ii) Chau’s transglutaminases because (a) Yan et al. in view of Wang et al. and evidenced by Zhu et al. teach a crosslinked polymer matrix comprising crosslinked type I collagen derived from bullfrog skin described above and (b) Chau et al. teach the benefits of transglutaminase-mediated cross-linked type I collagen comprising enhanced attachment, spreading and proliferation of cells to facilitate wound healing as well as slowing down collagen degradation leading to improvement of its in vivo efficacy as a biomaterial (p6527, conclusion col 1-2). The combination would have reasonable expectation of success because both Yan et al. and Chau et al. tach crosslinking collagen for medical use.
Response to Arguments
Applicant's arguments filed 9/8/2025 have been fully considered but they are not persuasive. See response to arguments above.
3. Claims 1-6, 8-9, and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Yan et al. in view of Wang et al. and evidenced by Zhu et al. as applied to claims 1-6, 11-12 and further in view of Cardoso et al. (Journal of Nanobiotechnology 2014, 12:36, previously cited 1/31/2023).
Claims 8-9 are directed to the polymeric material further comprising an antibacterial compound of silver nanoparticles.
Yan et al. in view of Wang et al. and evidenced by Zhu et al. suggest a cross-linked non-mammalian type I collagen polymer matrix used for drug delivery (Yang et al. p12, para 3-4; Wang et al. p2, col 1, para 3).
Yan et al. in view of Wang et al. and evidenced by Zhu et al. do not teach the collagen polymer matrix further comprising an antibacterial compound.
Cardoso et al. teach “Collagen-based silver nanoparticles for biological applications: synthesis and characterization” (Title). Cardoso et al. teach synthesis of silver nanoparticles (AgNPs) stabilized with type I collagen (AgNPcol) to build a nanomaterial with biological utility (Abstract-Background). Cardoso et al. teach the ability of AgNPs to control bacterial activity relies on the interactions with three major structural components of the bacteria: namely peptidoglycan in the cell wall, DNA, and proteins, by mainly affecting the enzymes involved in the electron transport chain (p2, col 1, para 4-5). Cardoso et al. further teach AgNPcol (1:6 molar ratio) for inhibiting the growth of bacteria was comparable to that of AgNO3 (p5, col 1, para 2) shown in Table 2 as follows (p5, Table 2), reading on claims 8-9.
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One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine Yan et al. in view of Wang et al. and evidenced by Zhu et al. with Cardoso’s silver nanoparticles because (a) Yan et al. in view of Wang et al. and evidenced by Zhu et al. suggest the use of a crosslinked bullfrog type I collagen polymer matrix for drug delivery (Yang et al. p12, para 3-4; Wang et al. p2, col 1, para 3) and (b) Cardoso et al. teach silver nanoparticles (AgNPs) beneficially stabilized by type I collagen (AgNPcol) to build a nanomaterial with anti-bacterial activity (Abstract-Background; p5, col 1, para 2; p5, Table 2). The combination would have reasonable expectation of success because the references teach a collagen scaffold for drug delivery.
Response to Arguments
Applicant's arguments filed 9/8/2025 have been fully considered but they are not persuasive. See response to arguments above.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
04-December-2025
/LI N KOMATSU/Primary Examiner, Art Unit 1658