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. Status of the Application The amendment and election of 6 March 2026 are entered. Claims 1-16 have been canceled. Claims 17-25 are pending. Claims 24 and 25 are withdrawn without traverse. Claims 17-23 are being examined on the merits. Election/Restrictions Applicant’s election without traverse of Group I and SEQ ID NO: 37 in the reply filed on 6 March 2026 is acknowledged. Claims 25 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6 March 2026. A search was made of SEQ ID NO: 37, which was determined to be free of the prior art. The search has been extended to other members of the genus, rejections for which are provided below. Nucleotide and/or Amino Acid Sequence Disclosures Summary of Requirements for Patent Applications Filed O n Or After July 1, 2022, T hat Have Sequence Disclosures 37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted: 1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying: a. the name of the XML file b. the date of creation; and c. the size of the XML file in bytes; or 2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying: a. the name of the XML file; b. the date of creation; and c. the size of the XML file in bytes. SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS: Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See p.35-39. Required response – Applicant must provide: A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of: • A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); • A copy of the amended specification without markings (clean version); and • A statement that the substitute specification contains no new matter. Specification The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Claim Rejections - 35 USC § 112 The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claim 23 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for a protein oligomer for use as a medicament for treating and ameliorating a disease from the list as claimed , does not reasonably provide enablement for a protein oligomer for use as a medicament for preventing a disease from the list as claimed . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. “[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech Inc. v. Novo Nordisk 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997); In re Wright 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); See also Amgen Inc. v. Chugai Pharm. Co. , 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir. 1991); In re Fisher 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Further, in In re Wands 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988) the court stated: Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman [230 USPQ 546, 547 (BdPatAppInt 1986)]. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredict ability of the art, and (8) the breadth of the claims. A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright , 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Nature of the Invention The invention is drawn to a protein oligomer based upon more than one NC-1-Fc monomers. The invention contains an intended use that includes treating, ameliorating, and preventing a long list of diseases. Breadth of the Claims The claim is not especially broad with respect to the protein oligomer, but is broad with respect to the intended use of the compound both in terms of the actual diseases as well as encompassing both treatment and prevention. State of the Prior Art The prior art does not generally recognize that all of the claimed diseases may be prevented through a protein oligomer comprising monomeric NC-1-Fc constructs. No such “silver bullet” exists that targets all of the claimed diseases such that prevention is achieved through the various species as claimed. As noted below, the prior art in US 2014/0302026 A1 and Shan et al. PLoS ONE 11:e0160345 provide reasonable teachings to prepare a protein oligomer comprising monomeric NC-1-Fc constructs as claimed. Nothing in either reference reasonably leads to an expectation that the construct prevents the claimed diseases. Relative Skill of those in the Art The relative skill of those in the art is high. Predictability or Unpredictability of the Art There is a general lack of predictability in the pharmaceutical art. In re Fisher , 427, F. 2d 833, 166, USPQ 18 (CCPA 1970). Amount of Direction or Guidance Given The specification guides that prevention means “…the avoidance of the occurrence or re-occurrence of the disease referred to herein…”. While the re-occurrence portion might reasonably be enabled, the avoidance of the occurrence language encompasses what would ordinarily be associated with “prevention”. There is not guidance on how one of ordinary skill in the art establishes a reasonable expectation that any of the claimed diseases would occur such that preventing might be achieved by the claimed protein oligomer. Presence/Absence of Working Examples No working examples show prevention of disease. The Examples do show purification of various constructs and anti-cancer or anti-fibrotic activity of certain constructs. Quantity of Experimentation Necessary The onus is placed on the skilled artisan to establish that the claimed protein oligomers are preventative across all of the claimed conditions. This also requires that they have foresight on when those diseases might occur so that the occurrence can be avoided through administration of the claimed protein oligomer. The skilled artisan must also establish model systems for all of the claimed diseases. The level of experimentation required to not only determine whether occurrence might occur but also the various required model systems rises to the level of an undue burden. In view of the Wands factors as discussed above, it is the Examiner’s opinion that the claims are not fully enabled and one of skill in the art would have to engage in undue experimentation to practice the invention as claimed herein, without a reasonable assurance of success. 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 appl icant regards as his invention. Claims 17-24 are 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. At issue is usage throughout the claims of exemplary language including “e.g.”, “preferably”, and “such as”. The language is indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. This is similar to the situations as discussed in MPEP 2173.05(d). The following claims include the language as indicated above: Claim 17- lines 3 and 4 utilize “preferably” ; Claim 18- line 4 utilizes “preferably” ; Claim 20- line 2 utilizes “preferably” ; and Claim 23- lines 3 and 8 utilize “preferably”; lines 10, 11, 13, 16, and 20 utilize “e.g.”; line 18 utilizes “such as”; and line 19 utilizes “as well as”. The “preferably”, “such as”, and “e.g.” language in the context of each claim also gives rise to questions of broad ranges or limitations together with a narrow range or limitation that falls within the broad range or limitation, since the claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP 2173.05(c). The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claims, and therefore not required, or (b) a required feature of the claims. For the purposes of prior art, the language following each “preferably”, “such as”, or “e.g.” phrase will be interpreted as reflecting an exemplary feature of the claim and therefore not required of the prior art to read upon the claim as a whole. 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. Claims 17-24 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 2014/0302026 A1, published 9 October 2014, hereafter referred to as ‘026 ) and Shan et al. (PLoS ONE 11:e0160345, published 1 August 2016, hereafter referred to as Shan) . The ‘026 application discloses a fusion between an NC-1 monomer of human collagen 18 and an Fc domain of an immunoglobulin (see e.g. claim 28). The Fc domain can be from IgG1 (see e.g. [0034]). The difference between ‘026 and the claimed invention is that the ‘026 application does not disclose or suggest a monomeric Fc domain that also includes half-life extension mutations. The Shan art discloses investigation of monomeric Fc domains that maintain FcRn binding (see e.g. Introduction). The base IgG4 Fc template utilizes contains the mutations M252Y/S254T/T256E for half-life extension and a F405R mutation for monomerization (see e.g. Phage library design, selection and screening). Monomeric Fc is desirable for different receptor targeting (Ying et al. Mabs 6:1201-1210, published 30 October 2014). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the NC-1-Fc fusion of ‘026 could have been modified by utilizing the IgG4 Fc of Shan comprising M252Y/S2 54T/T256E/F405R in order to prepare a NC-1-Fc fusion where any oligomerization is mediated by the NC-1 domain rather than the Fc, and taking advantage of the half-life extension properties of the Fc fusion and mutations therein. The rationale is merely substituting one Fc domain for another known Fc domain with the goal of allowing the NC-1 portion to dictate oligomerization of the fusion protein rather than Fc. There would have been a reasonable expectation of success because ‘026 already claims an NC-1-Fc fusion protein such that one of ordinary skill in the art would expect substitution of one Fc domain with another Fc domain would still result in an NC-1-fusion. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. With respect to claim 20, the reasonable construct from ‘026 and Shan is NC-1-Fc. The residues 1-312 of SEQ ID NO: 37 align to the NC-1 from collagen 18 with 100% identity that is provided by ‘026 . Next is a linker region GGGGSGGGGS. Then residues 333-512 encompass the IgG Fc with the M252Y/S254T/T256E/F405R mutations that is provided by Shan. Even allowing for the lowest 70% identity threshold allows for 153 alterations to SEQ ID NO: 37, which is within the ranges provided for by the fusion of NC-1 of ‘026 with the mutant Fc of Shan. With respect to claim 19, the NC-1 domains oligomerize as indicated by ‘026 (see e.g. Abstract, claim 28). With respect to claim 20, the Fc of Shan does not induce ADCC or CDC (see e.g. Introduction). With respect to claim 21, the ‘026 art describes a hinge region that is cleaved by MMPs (see e.g. [0010], [0037]). With respect to claims 22-23, the “for use as a medicament” clause merely describes an intended use that does not structurally alter the protein oligomer provided by ‘026 and Shan. See MPEP 2111.02. Since ‘026 and Shan make obvious the underlying protein oligomer and the “for use” claim does not alter the protein oligomer, the ‘206 and Shan art still make the claims obvious in lieu of a structural change imposed by the intended use. With respect to claim 24, the ‘026 art indicates that additional means for treatment of an angiogenesis-related disease may be present including anti-angiogenic agents (see e.g. [0110]). This reasonably encompasses “another therapy” as found in the claim for treating fibrosis, fibrosis-associated disease, or MMP-related disease. Conclusion No claims are allowed. 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