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 .
Priority
The instant application (filed 03/24/2023) claims the benefit of the prior-filed Korean Application No. KR10-2022-0170847 (filing date 12/08/2022). Receipt of the foreign certified copy is acknowledged; however, an English translation of the foreign application was not provided.
Status of Application/Claims
The amendment, filed 12/22/2025, is acknowledged. Claims 1-11 and 15 are canceled. Claim 12 is currently amended. Claims 12-14 and 16-18 are currently pending and are examined on the merits herein.
Information Disclosure Statement
No new information disclosure statements (IDSs) are submitted.
Withdrawn Objections & Rejections
Regarding the Specification objection for title issues, applicant amendment has addressed the issue. Thus, the objection is withdrawn.
Regarding the Specification objection for sequence compliance issues, applicant amendment has addressed the issue. Thus, the objection is withdrawn.
Regarding the Specification objection for trade names and/or trademark compliance issues, applicant amendment has addressed the issue. Thus, the objection is withdrawn.
Regarding the claim 12 objection for minor informalities, applicant amendment has addressed the issue and the objection is withdrawn.
Regarding the rejections for claims 1-11 and 15 under 35 U.S.C. 101 for eligibility: Applicant amendment has addressed the issue and claims 1-11 and 15 are canceled. Thus, the rejection is withdrawn.
Regarding the rejection for claims 1 and 3-18 and the rejection for claim 2 under 35 U.S.C. 103 for obviousness: Claims 1-11, and 15 are canceled and the rejections are withdrawn for these claims. Regarding the rejection for claims 12-14 and 16-18 under 35 U.S.C. 103 for obviousness, the rejections are maintained in modified form.
Regarding the non-statutory double patenting rejections for claims 1-18: Claims 1-11 and 15 are canceled and the rejection is withdrawn for these claims. Regarding the rejection for claims 12-14 and 16-18 for double patenting, the rejection is maintained in modified form.
Claim Rejections - 35 USC § 103
(Maintained in Modified Form)
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.
Claims 12-14 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Hysensbio – WO2019132353A1 (herein referred to as Hysensbio); and in further view of Park et al. Tubular dentin regeneration using a CPNE7-derived functional peptide. Materials (2020), 13:4618, p.1-21 (herein referred to as Park); and in further view of Perestenko et al. The second C2-domain of copine-2, copine-6 and copine-7 is responsible for their calcium-dependent membrane association. FEBS Journal (2015), 282, p.3722-3736 (herein referred to as Perestenko); and, in further view of LifeProtein. N-terminal acetylation and C-terminal amidation. 6/18/2022. Internet – Wayback Machine. p.1-3 (herein referred to as LifeProtein).
Hysensbio teaches pharmaceutical compositions comprising CPNE4 protein (or a gene thereof), as well as methods comprising administration of CPNE4, for preventing or treating dentin-dental pulp disease or periodontal disease and for promoting the regeneration of dental pulp tissue or hard tissue including dentin, bones, and cementum (title; abstract; p.6-7; instant claims 12-14, and 16). Hysensbio also teaches a quasi-drug composition and a health functional food composition for preventing or alleviating (i.e., treating) dentin-dental pulp disease and/or periodontal disease (abstract; (p.5, [1]; instant claim 14). Hysensbio teaches that the dentin-dental pulp disease may be pulp necrosis (p.5, [3]), dentin hypersensitivity (i.e., applicant “dentin hyperesthesia”; p.10, [83]; instant claim 17). Hysensbio teaches that the periodontal disease may be gingivitis, periodontitis, periodontal pocket, or periodontitis (p.6, [27]; instant claim 18). Hysensbio teaches expression vectors used to express the CPNE4 gene/protein (i.e., the polynucleotide encoding the CPNE protein).
Regarding instant claim 12-i: Hysensbio does not teach that the treatment is a peptide fragment that consists of a 10-amino acid region of CPNE4 (i.e., applicant SEQ ID NO: 1; instant claims 12-13).
Park teaches tubular dentin regeneration using a functional 10-amino acid peptide derived peptide from copine-7/CPNE7 (i.e., “Cpne7-DP”; title). Park teaches that the amino acid sequence for Cpne7-DP is KYKQKRRSYK (p.3, para.5). Park teaches that the 10-mer sequence of CPNE7 (i.e., CPNE7-DP) is sufficient for inducing odontoblast-like differentiation (in vitro), mineralization (ex vivo), and tubular dentin formation (in vivo, in mammalian subjects) to promote dental regeneration in dental defects of various degrees; and, that the regenerated hard tissue demonstrates the characteristics of true dentin (abstract).
Perestenko teaches that the copine family of proteins contains nine members (CPNEs 1-9) with a similar domain structure, namely two N-terminal C2-domains (C2A and C2B) and a C-terminal A-domain (abstract). Further, Parestenko teaches the amino acid sequence for CPNE4, which encodes applicant’s SEQ ID NO: 1 10-mer peptide “KYKAKKKNYK”; as well as highlights that this 10-mer sequence is highly homologous to that of other copines, including Park’s CPNE7-DP described above (p.3, Fig.1-dotted line; p.5, Fig.2A-first dashed box).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hysensbio with the combined teachings of Park and Perestenko, by modifying the method of treatment using a CPNE4 protein (as taught by Hysensbio) to a method that uses the 10-mer peptide (as taught by Park) from the highly homologous CPNE4 10-mer amino acid linker (as taught by Perestenko) to arrive at the instantly claimed invention, in order to receive the benefit that the 10-mer linker region (as taught by Park and Perestenko) of CPNE4 (as taught by Hysensbio) is sufficient for promoting regeneration. One of ordinary skill in the art would have a reasonable expectation of success because both CPNE4 (as taught by Hysensbio) and the high homology linker region of CPNE7 (as taught by Park) promote regeneration of hard tissue and dental pulp to prevent or treat periodontal disease and Parestenko teaches the 10-mer high homology linker region for copine proteins. Regarding instant claim 12-ii: The combination of Hysensbio/Park/Perestenko does not teach that the peptide is N-terminal or C-terminal acetylated or amidated (instant claim 12-ii).
LifeProtein teaches N-terminal acetylation and C-terminal amidation of peptides, wherein these modifications provide the advantage of increased metabolic stability and resistance to enzymatic degradation (p.1-2; instant claim 12).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Hysensbio/Park/Perestenko and LifeProtein by modifying the peptide to have an N- or C-terminal amidation (as taught by LifeProtein) and to administer the peptide in a method for treating dentin-dental pulp disease or periodontal disease (as taught by Hysensbio) to arrive at the instantly claimed invention, in order to receive the expected benefit (as taught by LifeProtein) that modifying the peptide (as taught by Hysensbio/Park/Perestenko) would provide the predictable advantage of increased metabolic stability and resistance to enzymatic degradation (as taught by LifeProtein).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
11376310
(Maintained in Modified Form)
Claims 12-14 and 16-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-10, 14, 18-22, and 25-30 of U.S. Patent No. 11376310 (herein referred to as Pat’310) in view of Park and Perestenko; and, further in view of LifeProtein. N-terminal acetylation and C-terminal amidation. 6/18/2022. Internet – Wayback Machine. p.1-3 (herein referred to as LifeProtein).
Pat’310 teaches a method for preventing and/or treating dentin-dental pulp disease or periodontal diseases in a subject by administering a composition comprising CPNE4 protein, wherein the composition promotes regenerating a hard tissue (Pat’310 claims 1-2; instant claim 12). Pat’310 teaches that the composition is a pharmaceutical composition (Pat’310 claims 5 and 25). Pat’310 teaches that the dentin-dental pulp disease can be dental hypersensitivity (i.e., hyperesthesia), pulp hyperemia, pulpitis, pulp degeneration, pulp necrosis, and gangrenous pulp (Pat’310 claims 6, 18, and 26; instant claim 17). Pat’310 teaches that the periodontal disease can be gingivitis, periodontitis, periodontal pocket, or periodontal abscess (Pat’310 claims 7 and 19; instant claim 18). Pat’310 teaches that the hard tissue is dentin, bone, and cementum (Pat’310 claims 10, 14, 22, and 29-30; instant claim 16). Pat’310 teaches that the composition is a dietary supplement or foodstuff (Pat’310 claims 8-9, 20, and 28). Pat’310 teaches administration of a polynucleotide encoding the CPNE4 protein using a vector (Pat’310 claims 13, 21, and 29-30).
Pat’310 does not teach that the treatment is a 10-mer peptide fragment of CPNE4 (instant claims 1, 12, 13, and 15); that the peptide is N-terminal or C-terminal acetylated or amidated (instant claim 12).
Regarding claims 12 and 13: Park teaches tubular dentin regeneration using a functional 10-amino acid peptide derived peptide from copine-7/CPNE7 (i.e., “Cpne7-DP”; title). Park teaches that the amino acid sequence for Cpne7-DP is KYKQKRRSYK (p.3, para.5). Park teaches that the 10-mer sequence of CPNE7 (i.e., CPNE7-DP) is sufficient for inducing odontoblast-like differentiation (in vitro), mineralization (ex vivo), and tubular dentin formation (in vivo, in mammalian subjects) to promote dental regeneration in dental defects of various degrees; and, that the regenerated hard tissue demonstrates the characteristics of true dentin (abstract).
Perestenko teaches that the copine family of proteins contains nine members (CPNEs 1-9) with a similar domain structure, namely two N-terminal C2-domains (C2A and C2B) and a C-terminal A-domain (abstract). Further, Parestenko teaches the amino acid sequence for CPNE4, which encodes applicant’s SEQ ID NO: 1 10-mer peptide “KYKAKKKNYK”; as well as highlights that this 10-mer sequence is highly homologous to that of other copines, including Park’s CPNE7-DP described above (p.3, Fig.1-dotted line; p.5, Fig.2A-first dashed box).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Pat’310 with the combined teachings of, Park, and Perestenko, by modifying the CPNE4 protein (as taught by Pat’301) to the 10-mer peptide (as taught by Park) from the highly homologous CPNE4 10-mer amino acid linker (as taught by Perestenko) to arrive at the instantly claimed invention, in order to receive the benefit that the 10-mer linker region (as taught by Park and Perestenko) of CPNE4 (as taught by Pat’310) is sufficient for promoting regeneration. One of ordinary skill in the art would have a reasonable expectation of success because both CPNE4 (as taught by Pat’310) and the high homology linker region of CPNE7 (as taught by Park) promote regeneration of hard tissue and dental pulp to prevent or treat periodontal disease and Parestenko teaches the 10-mer high homology linker region for copine proteins.
Regarding claims 12-14 and 16-18: LifeProtein teaches N-terminal acetylation and C-terminal amidation of peptides, wherein these modifications provide the advantage of increased metabolic stability and resistance to enzymatic degradation (p.1-2; instant claims 12-14 and 16-18).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Pat’310/Park/Perestenko and LifeProtein by modifying the peptide to have an N- or C-terminal amidation (as taught by LifeProtein) and to administer the peptide in a method for treating dentin-dental pulp disease or periodontal disease (as taught by Pat’310) to arrive at the instantly claimed invention, in order to receive the expected benefit (as taught by LifeProtein) that modifying the peptide (as taught by Pat’310/Park/Perestenko) would provide the predictable advantage of increased metabolic stability and resistance to enzymatic degradation (as taught by LifeProtein).
Response to Arguments
Regarding the rejections for claims 12-14 and 16-18 under 35 U.S.C. 103 for obviousness, applicant traverses. Applicant states that there is no teaching in Hysensbio that CPNE4 10-mer (i.e., the CPNE4 fragment encoded by instant SEQ ID NO: 1) retains regenerative activity (see applicant arguments filed 12/22/2025, p.8, para.1). Applicant additionally states that Park does not show any other copine 10-mer other than CPNE7 works this way (see applicant arguments, p.8, para.3). Applicant also states that Perestenko’s disclosure of the homologous region consisting of the 10-mer region does not reliably predict biological equivalence of small fragments. Applicant also states that there is no motivation for modifying Park’s teaching of the CPNE7-DP to that of instant SEQ ID NO: 13 (see applicant arguments, p.9, para.3).
Firstly, the basis of the obviousness rejection in the non-final office action filed 09/22/2025 was on the basis of rejecting instant SEQ ID NO: 1 which encodes for a 10-mer linker fragment of CPNE4, rather than instant SEQ ID NO: 13. Regarding the rejection based on instant SEQ ID NO: 1 as it pertains to instant claim 12, where there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success. The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention (MPEP 2143.02-I). Obviousness does not require absolute predictability, but at least some degree of predictability is required. Evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness (MPEP 2143.02-II). SEQ ID NO: 1 represents an amino acid fragment from the sequence of the full-length human Copine-4 protein, which is known in the art (see Uniprot.org, Q96A23, CPNE4_Human, residues 268-278); thus, the 10-mer fragment of instant SEQ ID NO: 1 is also known in the art as this is a fragment of the naturally occurring CPNE4 protein. The full-length CPNE4 taught by Hysensbio, as well as the full-length CPNE7 and CPNE7-DP 10-mer taught by Park, exhibit the ability to promote regeneration (see Hysensbio and Park abstracts). Not only does Park teach that the CPNE7-DP fragment is in the exact region of instant SEQ ID NO: 1, but Perestenko also teaches the linker region for copine proteins and specifically highlights a region of high homology which consists of the exact 10-mer region of CPNE4 encoded by instant SEQ ID NO: 1 (see Perestenko, Fig.3A-dashed box, left side). Additionally, Park teaches that this 10-mer linker fragment in CPNE7 is sufficient for providing a benefit of inducing regeneration. Thus, the combination of prior art teachings provides one of ordinary skill in the art with a reasonable expectation of success that the analogous 10-mer region of CPNE4 would be sufficient to promote regeneration, because full-length CPNE4 and CPNE7 as well as the exact corresponding linker region of CPNE7 all result in promoting regeneration. Park also teaches that the CPNE7-DP 10-mer fragment proved advantageous in providing a more stable and potent cell-penetrating peptide (p15, para.5); thus, the combination of teachings also supports a reasonable expectation of success that using shorter 10-mer copine linker fragments would likely provide for additional benefits of stability and cell-penetration. Additionally, Lee et al. Identification of cell-penetrating osteogenic peptide from copine-7 protein and its delivery system for enhanced bone formation (2019), 107, p.2392-2402 (herein referred to as Lee) teaches that short peptides derived from CPNE-7 (a member of the copine family) exhibit cell penetration with low cytotoxicity (p.2393, col.1, para.4). These features appear to be inherent to the short length of the peptides, rather than markedly different characteristics between a copine fragment and the full length copine protein (p.2396, Fig.1). This further supports that one of ordinary skill would have a reasonable expectation of success that a short fragment from the specific 10-mer region of the linker of CPNE4 would likely be able to penetrate the cell and would be sufficient to promote regeneration, especially because Hysensbio teaches that CPNE4, specifically, is known to promote regeneration. Further, applicant has provided no evidence showing there was no reasonable expectation of success to support a conclusion of nonobviousness.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jami M Gurley whose telephone number is (571)272-0117. The examiner can normally be reached Monday - Friday, 8am - 4pm.
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, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647