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. Applicant’s amendment, filed on 10/11/2023, is acknowledged. Claims 5, 7, 10, 11, 14, 17, 18, 21-27, 29, 30, 32, 33, 35, 36, 38, 40-52, and 55-58 are cancelled. Claims 1-4, 6, 8, 9, 12, 13, 15, 16, 19, 20, 28, 31, 34, 37, 39, 53, and 54 are currently pending. Claims 1 and 2 are independent claims. Election/Restrictions Applicant’s election of Group I, claims 1-4, 6, 8, 9, 12-15, 19-22, 25, 26, 31-33, 36, and 53 ; and the Species of: i ) SEQ ID NO: 110; ii) the conjugate formula of claim 12 ; iii) an cleavable linker comprising an oligopeptide with a C-terminal Pro residue ; and iv) a cytotoxic agent drug moiety in the reply filed on 2/2/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). The conjugate formula recited in claims 13 does not read on the elected species of conjugate formula. The drug moieties recited in claims 37 and 39 do not read on the elected species of drug moiety. Claims 13, 37, 39, and 54 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species. Claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 are under examination as reading on a therapeutic conjugate comprising a n acutely toxic drug moiety to a half-life extension moiety via a n enzyme cleavable linker. Priority Applicant’s claim for the benefit of a prior-filed US 63/ 108,046 filed October 30, 2020 and US 63/197, 935 , filed June 7, 2021, is acknowledged. Information Disclosure Statement The information disclosure statements (IDS) submitted on 7/27/2023 and 2/02/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties. 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. Claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention. Claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 encompass therapeutic conjugates comprising linkers with a partial structure at best and the function of “ enzyme cleavable linker”, including generic enzyme cleavable linkers with no recited structure (claims 1-4, 6, 8, 9, 12, 28, 31, 34, 37, and 53), oligopeptides and oligopeptides with a C-terminal Pro (claims 15 and 16), and generic protease recognition sequences with no recited structure (claims 19 and 20) . Additionally, claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 encompass therapeutic conjugates comprising moieties with a partial structure at best and the functions of “half-life extension moiety” and “serum half-life of the therapeutic conjugate in vivo is at least 48 hours” (claims 1, 3, 4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 ), or “half-life extension moiety” and “serum half-life of the therapeutic conjugate in vivo is extended by more than 2-fold relative to circulating serum half-life of a free therapeutic moiety” (claim 2). Claim 12 additionally encompasses a broad genus of linkers with no recited structure and the function “self- immolative linker or bond”. Regarding the broadly claimed genera of half-life extension moieties and enzyme-cleavable linkers, t he specification fails to provide adequate written description support for a genus of linkers with a partial structure at best having the desired functional properties required to practice the claimed function “ enzyme -cleavable linker” (claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 ) ; and the specification fails to provide adequate written description support for a genus of moieties with a partial structure at best and the function of “half-life extension moiety” (claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 ) . The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns ., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) ( en bane). A "sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id. "[F] unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id. "A sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added). Regarding the claimed genera of linkers with a partial structure at best having the desired functional properties required to practice the claimed function “enzyme-cleavable linker” (claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53) , t he specification discloses over a hundred different protease enzymes (pg. 44-67), and discloses specific examples of protease-cleavable substrate oligopeptide sequences (pg. 67 and 68), including MMP and thrombin substrates (pg. 68, SEQ ID NO: 199-221), and FAPα cleavable linker examples that require a proline ( such as (d)Ala-Pro and Ser-(d)Ala-Pro, Fig. 1, 6, 11, 14 , and 28). Regarding the claimed genera of moieties with a partial structure at best and the function of “half-life extension moiety” (claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53) , the instant specification discloses that serum proteins such as fibronectin, transferrin, and HSA, or an antibody Fc domains can function as half-life extension moieties (pg. 16-18). The instant specification further discloses that half-life extension moieties can also be moieties that specifically bind to serum proteins such as HSA. The instant specification discloses sequences of affimers that specifically bind to HSA and can function as half-life extension moieties (SEQ ID NO: 110-132, Tables 1-3), however does not disclose any other structures (small molecules, aptamers, etc.) that bind to serum proteins and has the function of “half-life extension moiety”. With respect to representative number of species, see AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 Il(A)(3)(a))(ii): A representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See Abb Vie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly , 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie , 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., k off ) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.). In the instant case, regarding the claimed genera of linkers with a partial structure at best having the desired functional properties required to practice the claimed function “enzyme-cleavable linker” (claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53) , the instant specification discloses peptide sequences of known oligopeptides that are cleaved by MMP proteases, thrombin, and FAPα serine protease, all of which are specific sequences that are recognized by the proteases. For example, all of the FAPα cleavable sequence examples have a proline in the substrate recognition sequence. No other representative species are disclosed , including linkers with SRS structures that include non-natural amino acid residues , that have the function of “ enzyme-cleavable linker ”. Th ese limited number of sequences do does not sufficiently represent the broad ly claimed genera of linkers with a partial structure at best and the recited function of “ enzyme-cleavable linker ”. No other cleavable substrates to any of the other listed enzymes in the specification are disclosed. Regarding the claimed genera of moieties with a partial structure at best and the function of “half-life extension moiety” (claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53) , the instant specification discloses a subgenus of moieties that bind to serum proteins, anti-HSA affimers , however this subgenus does not sufficiently represent the broadly claimed genus of moieties with a partial structure at best and the function of “half-life extension moiety” recited in claims 1-4, 6, 12, 15, 16, 19, 20, 28, 31, 34, and 53 , which includes any small molecule, aptamer, polypeptide, antibody, etc., with the recited functions. Additionally, instant claims 8 and 9 recites a more limited subgenus of affimers with no structure (claim 8) or that are at least 70%, 80%, or 90% identical to the instantly elected SEQ ID NO: 110 (claim 9) that have the function of “half-life extension moiety” by specifically binding to HSA. Regarding claim 9, t he total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula: N!*19A N-A ! A! Where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. For a polypeptide that is 112 residues in length with 11 allowed substitutions (10% variation within SEQ ID NO: 110 allows for 11 substitutions) , there would be 112!*19(11) 112-11 ! 11! Which is approximately 1.74 x10 32 variants , including variants that have amino acid substitutions in the loop regions that are critical for specific antigen binding. The limited number of affimer examples disclosed does not sufficiently represent this diverse genus of anti-HSA affimers . Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed enzyme- cleavable linkers and half-life extension moieties to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC , No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function. Given the broadly claimed class es of enzyme- cleavable linkers and half-life extension moieties , and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class es of enzyme- cleavable linkers and half-life extension moieties , the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims . AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163. Regarding the claimed genera of linkers with a partial structure at best having the desired functional properties required to practice the claimed function “ enzyme -cleavable linker” ( claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 ), the instant specification discloses consensus oligopeptide sequences that are each cleaved by a certain protease or class of proteases (pg. 68). Additionally, the prior art teaches there are specific peptide substrate sequences that are recognized by different protease enzymes. For example, regarding FAPα cleavable linkers for example, FAPα consensus peptide sequences have been discovered in the prior art. Aggarwal et al. ( Biochemistry. 2008 Jan 22;47(3):1076-86. doi : 10.1021/bi701921b. Epub 2007 Dec 21 ) teaches (Introduction): “ … we present results using liquid chromatography/tandem mass spectrometry (LC/MS/MS) to generate a complete map of FAP cleavage sites within recombinant forms of human collagen I derived gelatin. We have synthesized selected peptides on the basis of these cleavage maps and analyzed them for hydrolysis by FAP to identify peptides that could be used to target cytotoxins to FAP-expressing tumor tissue. ” Aggarwal et al. identified the following sequences that were found to be FAPα cleavable peptide sequences: (d)Ala-Pro (pg. 4, final ¶), PPGP, (D/E)-(R/K)-G-(E/D)-(T/S)-G-P, and DRGETP (Abstract). Additionally, Ji et al. ( Angew Chem Int Ed Engl. 2016 Jan 18;55(3):1050-5. doi : 10.1002/anie.201506262. Epub 2015 Aug 17 ) identified another FAPα cleavable peptide sequence, which is GPAX, where X is any amino acid sequence (pg. 1050). Other than these consensus sequences, no other structure-function relationship between a peptide sequence and identification as a FAPα-cleavable substrate sequence. Regarding the claimed genera of moieties with a partial structure at best and the function of “half-life extension moiety” (claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53) , the specification lists multiple affimer sequences that have the function of specifically binding to HSA that have the function of “half-life extension moiety” (Tables 1-3). No other serum protein binding moieties, such as antibodies, small molecules, aptamers, etc. have been described, and no structure-function relationship between these broad genera of serum protein binding moieties and the function of “half-life extension moiety”. For these broadly recited genera of serum protein binding moieties with no recited structure ( claims 1-4, 6, 12, 15, 16, 19, 20, 28, 31, 34, and 53 ), t he specification at best describes a plan for making half-life extension moieties that bind to serum proteins , and then identifying those that satisfy the claim limitations, but a mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories , 97 USPQ2d 1870 (Fed. Cir. 2011). Additionally, the disclosure does not provide information sufficient to establish that a skilled artisan would understand how to identify the species of binding moieties (antibodies, scFvs , sdAbs , aptamers, etc.) capable of binding to any target ( claims 1, 2, 6, 12, 15, 16, 19, 20, 28, 31, 34, and 53 ), any “serum protein” (claim 3), or the serum proteins recited in claims 4 and 6 to lead to the function of “half-life extension moiety” that the claims require. Without more in the disclosure, such as characteristics of exemplary binding moieties other than affimers that allow them to bind to particular targets, the mere fact that binding moieties that can bind to proteins to act as a “half-life extension moiety” in general bind does not demonstrate possession of the broad genera of binding molecules encompassed by the claims. Furthermore, the disclosure fails to disclose a method to distinguish those binding molecules that are in capable of binding the recited targets from ones that do. Regarding the broad genera of biocompatible polymers with the function of “half-life extension moiety”, which includes the recited function “serum half-life… in vivo is at least 48 hours” (claim 3; see discussion of claim scope supra ), the instant specification discloses broad classes of polymers that can be biocompatible (pg. 41-42), however does not distinguish which specific structures have the recited half-life extension functions recited the claims, and does not disclose any relationship between a polymer’s structure and the function of “half-life extension moiety”. The prior art also teaches that there is unpredictability between a polymer’s structure and the function of “half-life extension moiety”. Podust et al. ( J Control Release. 2016 Oct 28;240:52-66. doi : 10.1016/j.jconrel.2015.10.038. Epub 2015 Oct 30 ), teaches that different XTEN structures can extent the half-life of therapeutics, however the half-life ranges from under 2.5 hours to over 72 based on the specific XTEN structure (Table 2). Additionally, Reichard et al. ( Pharm Res. 2016 Dec;33(12):2954-2966. doi : 10.1007/s11095-016-2017-y. Epub 2016 Sep 12 ) teaches that PEGylation of can increase the serum half-life of a therapeutic to 25 hours (Table II), however this does not fall within the scope of the instant claims, as the function of “half-life extension moiety” recited in claim 1 includes a serum half-life greater than 48 hours. Neither the instant specification nor the prior art discloses sufficient structure identifying characteristics to identify which “biocompatible polymer” species in the broadly recited genus have the recited function of “half-life extension moiety”, or how to distinguish between structures with this function and those without. Additionally, regarding the broadly claimed genera anti-HSA affimers with a partial structure at best (claim 8), and with significant variation in the critical loop sequences responsible for specific binding (claim 9), the specification discloses specific anti-HSA affimer structures, defined by their amino acid sequences, that have the function of “half-life extension moiety”. Neither the instant specification nor the prior art provide a structure-function relationship between an affimer’s amino acid sequence and the function of specifically binding HSA to be a “half-life extension moiety”. Furthermore, Stadler et al. ( Protein Eng Des Sel. 2011 Sep;24(9):751-63. doi : 10.1093/protein/gzr019. Epub 2011 May 25 ) teaches that affimers based on the stefin A peptide scaffold can have their loop regions vary in amino acid sequence to generate combinatorial libraries that can be screened for specific binding to different targets, much like antibodies (Introduction): “ [a] new variant scaffold, S QT ( Stefin A Quadruple Mutant—Tracy), is able to present a range of peptides and shows thermostability similar to that of the parental Stefin A protein. Peptide aptamers, which we now call Scannins , presenting ‘epitope tag’ peptides in the N-terminus, loop 1 and/or loop 2 of SQT … Scannins are likely to be broadly useful in presenting a wide range of peptides for interaction using three independent sites, with protein binding affinities and stabilities that can be tuned to the experimental setting . ” The prior art teaches that affimers based on stefin A have a constant scaffold with varied N-terminal, loop 1, and loop 2 regions that determine specific binding to different targets. Tiede et al. ( Elife . 2017 Jun 27;6:e24903. doi : 10.7554/eLife.24903 ) demonstrates these loop regions (top of figure below) vary in sequence, and therefore size and 3-dimensional structure, to determine specific binding (Fig. 1): Neither the instant specification nor the prior art disclose a relationship between the amino acid sequences of an affimer’s variable loop regions and HSA binding that leads to the function of “half-life extension moiety”. The only structure function relationship is to list specific affimer sequences that have this function. Additionally, the current state of the art teaches that there is unpredictability in determining which anti-HSA affimer structures that are defined by their amino acid sequences would have the recited function of “half-life extension moiety”. Gomes et al. ( avacta.com/wp-content/uploads/2019/10/POS018_Serum_Albumin.pdf ; first available 6/02/2023) teaches that five different anti-HSA affimers extend serum half-life in the range of 24.3-38.2 hours (Table 2), and therefore none of these different anti-HSA affimer species would fall within the scope of the claims, as claim 1 also recites “serum half-life… in vivo is at least 48 hours”. Neither the prior art nor the instant specification discloses how to distinguish between different defined affimer structures and the recited function of “half-life extension moiety”. Undue experimentation would be required by one with ordinary skill in the art to determine this, as one would need to test each individual affimer structure (defined by their amino acid sequence) to determine if: 1) the affimer extends the serum half-life of a therapeutic; and 2) if the half-life is greater than 48 hours, as not all anti-HSA affimers would extend serum half-life by this amount. Regarding the broadly claimed genus of linkers with no structure and the function of “self- immolative linker or bond” in claim 12, the instant specification discloses general structures that can possibly lead to functional self- immolative linkers (pg. 71-73) and provides five working examples self- immolative linkers with specific structures in Fig. 9, 12, 13, 15, and 16, however these limited examples do not sufficiently represent the claimed genus of linkers with no recited structure and the function of “self- immolative linker or bond”. Additionally, neither the instant specification nor the prior art provides sufficient structure-function relationship between a linker’s structure and the function of “self- immolative linker or bond”. For example, Xu et al. ( Eur J Med Chem. 2024 Dec 5;279:116928. doi : 10.1016/j.ejmech.2024.116928. Epub 2024 Sep 30 ) teaches principles of design of self- immolative linkers used in prodrugs (Section 2): “ [a] t the heart of the design of self- immolative prodrugs lies the incorporation of a trigger moiety, a chemical entity that initiates the cascade of decomposition reactions leading to drug release … the trigger moiety must be carefully tailored to ensure selective activation within the target tissue while minimizing off-target effects … the design of self- immolative prodrugs encompasses the selection of appropriate drug payloads and linker chemistries to achieve optimal pharmacokinetic and pharmacodynamic properties ”. Xu et al. further teaches that specific self- immolative linker structures differ based on the cleavable substrate that they are incorporated in and the specific payload/therapeutic that is used. For example, different self- immolative linkers have been found to function in cathepsin-B cleavable prodrugs based on the drug that is intended to be released (Section 4.2.1, Fig. 1), while PABC has been found to act as a self- immolative linker in MMAE-based prodrugs (Section 4.2.3, Fig. 2). Thus, undue experimentation would be required by one with ordinary skill in the art to determine which structures in the broadly claimed genus would have the function of “self- immolative linker”, or how to distinguish between structures with this the function and those without. Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of anti-TMPRSS6 antibodies or antigen binding fragments thereof falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406. Claims 1-4, 6, 8, 9, 12, 15, 16, 19, 20, 28, 31, 34, and 53 do not meet the requirements of 35 U.S.C. 112(a) for written description. Vas-Cath Inc. v. Mahurkar , 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co . 43 USPQ2d 1398. Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed. 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 9 is 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. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad sequence identity “at least 70%”, followed by the narrower ranges “at least 80%” and “at least 90%”. 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 1-4, 6, 12, 15, 16, 19, 20, 28, and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Bachovchin et al. (U.S. Patent 9,956,297) in view of Müller et al. ( MAbs . 2012 Nov-Dec;4(6):673-85. doi : 10.4161/mabs.22242). Claims 1 and 2 claim a therapeutic agent comprising a therapeutic moiety linked to a half-life extending moiety via an enzyme-cleavable domain, wherein the therapeutic does not comprise a cell binding moiety that binds to a cell surface protein of a cell with a Kd of 1x10 -6 M or less, and wherein the serum half-life of the therapeutic is at least 48 hours (claim 1) or is at least 2-fold longer that the therapeutic without the half-life extending moiety (claim 2). Bachovchin et al. teaches FAP-activated proteasome inhibitor therapeutic conjugates comprising a Ser-(d)Ala-Pro FAPα cleavable linker (i.e., “enzyme-cleavable linker”) bound to a proteasome inhibitor (Col. 22, also see below): Bachovchin et al. teaches that the proteasome inhibitor drug can also comprise bortezomib (Col. 24, lines 5-10). Bachovchin et al. teaches that proteasome inhibitors such as bortezomib have acute toxicity and can cause toxicities such as peripheral neuropathy and hematologic toxicities (Col. 2, lines 4-8). Bachovchin et al. additionally teaches methods of treating cancer comprising administration of these therapeutic compounds (claims 1 and 2). Bachovchin et al. does not teach the conjugates linked to half-life extension moiety. M ü ller et al., in the same field of endeavor, teaches that removal of the Fc domain or other half-life extending moieties in a therapeutic, which may pose issues when used to treat disease (Introduction): “ [t] he challenge being that the loss of the Fc domain and the reduction in size results in more rapid clearance of the molecules, which may be advantageous for diagnostic imaging, but is far from optimal for the treatment or management of chronic disease … ” M ü ller et al. teaches anti-HSA IgNAR binding domains that can be used to extent the serum half-life of therapeutics that it is conjugated to (Introduction): “ … we isolated a high affinity anti - HSA VNAR binding domain through immunization of a novel shark species … this is the first report of the use of this class of binding domain to affect in vivo retention by increasing the sera half-life of a fused domain … ” M ü ller et al. further teaches potential benefits of increasing the serum half-life of therapeutics (Introduction): “ [t] ailoring the half-life of therapeutic drugs would negate the requirement for multiple administrations, hence minimizing accumulative damage to the patient, increasing patient compliance and reducing the overall dosing regimen. Importantly, it would also open the opportunity to develop short-lived molecules, previously deemed unsuitable for drug development, into effective therapeutic agents . ” M ü ller et al. teaches that fusion of an anti-HSA IgNAR to another VNAR domain that does not bind a target increases that serum half-life (pg. 675): “ [t] o determine the efficacy of the anti-HSA VNAR domains to increase the serum half - life of another unrelated VNAR domain, fusions consisting of both N-terminally and C-terminally linked HSA-binding E06 to a random naïve VNAR domain known as 2V (sequence shown in Fig. 3B) were constructed … ”. The anti-HSA VNAR fusion constructs increased serum half-life by over 100-fold in mice when compared to the conjugate without the anti-HSA VNAR, and the serum half-life was over 150 hours in nonhuman primates (Table 2). M ü ller et al. further teaches (Discussion): “ [t] he lead clone isolated exhibited the ability to improve the PK parameters of a fused tandem VNAR domain exhibiting serum half-life values equating to that of albumin itself. This study provides the potential of these single binding domains to … act as tools to improve the PK properties of other biologic proteins. ” It would have been obvious to one of ordinary skill of the art, before the effective filing date of the instant application, to have modified the conjugate taught by Bachovchin et al. in view of M ü ller et al. to fuse the anti-HSA VNAR of M ü ller et al. to the FAPα enzyme-activatable protease inhibitor of Bachovchin et al. (i.e., the limitations of instant claims 1 and 2) with a reasonable expectation of success, as M ü ller et al. teaches a method of conjugating the anti-HSA VNAR to other peptides, and the therapeutic of Bachovchin et al. has a peptide FAPα cleavable peptide moiety that can be fused to the anti-HSA VNAR (thus, the conjugate would have the anti-HSA VNAR conjugated to the protease inhibitor via the FAPα cleavage site). One would have been motivated to make this change to increase the half-life of the FAPα activatable protease inhibitor of Bachovchin et al., which would reduce the frequency of administration and improve patient compliance and quality of life. The combined references do not teach the conjugate further comprising a moiety that binds to a cell surface protein, meeting these limitations. Regarding claims 3, 4, and 6, the anti-HSA VNAR of M ü ller et al. is a shark antibody molecule that binds to HSA, meeting the claim limitations. Regarding claim 12, Bachovchin et al. further teaches the following FAPα cleavable protease inhibitor prodrug formula A-B, wherein A is the FAPα cleavable substrate and B is the proteasome inhibitor moiety (Col. 6, lines 61-33). Bachovchin et al. additionally teaches this formula can further comprise a self-eliminating (i.e., “self- immolative ”) linker such as PABC between A and B (Col. 15, lines 45-51). M ü ller et al. teaches the anti-HSA VNAR half-life extension moiety is fused to a conjugate via a peptide linker GGGGS (pg. 682, right column, first ¶). Fusion of the VNAR of M ü ller et al. to the protease inhibitor prodrug with the self- immolative linker taught by Bachovchin et al. via the FAPα cleavable linker would yield a formula of X-L 2 -SRS -L2 -DM , wherein X is the anti-HSA VNAR half-life extension moiety, L2 is a GGGGS linker, SRS is the FAPα cleavable SRS, L2 is the self- immolative linker, and DM is the proteasome inhibitor drug moiety, meeting the claim limitations. Regarding claims 15, 16, 19, and 20, the FAPα serine protease cleavage site taught by Bachovchin et al. is Ser-(d)Ala-Pro, meeting the claim limitations. Regarding claim 28, Bachovchin et al. teaches that the proteasome inhibitors are acutely cytotoxic once activated (Col. 40, lines 44-46): “ …pro-drug v ersion of a bortezomib-like cytotoxic agent designed to more selectively target the proteasome in solid tumors…” , meeting the claim limitations. Regarding claim 53, Bachovchin et al. teaches pharmaceutical compositions comprising the therapeutic and an acceptable excipient (Col. 23, lines 1-4). Therefore, the invention as a whole was prima faci e obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. Claims 31 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Bachovchin et al. ( supra ) and Müller et al. ( supra ), as applied to claims 1-4, 6, 12, 15, 16, 19, 20, 28, and 53 a bove, and further in view of Walsh et al. ( PLoS One. 2013;8(3):e58860. doi : 10.1371/journal.pone.0058860. Epub 2013 Mar 12) and Poplawski et al. (J Med Chem. 2011 Apr 14;54(7):2022-8. doi : 10.1021/jm100972f. Epub 2011 Mar 9), as evidenced by MCE ( Talabostat safety data sheet; file.medchemexpress.com/batch_PDF/HY-13233A/Talabostat-mesylate-SDS-MedChemExpress.pdf) The combined teachings of Bachovchin et al. and M ü ller et al. are discussed supra . The combined references do not teach the therapeutic moiety as Val- boroPro , which is an iDASH inhibitor with acute toxicity (i.e., the limitations of claims 31 and 34). Walsh et al., in the same field of endeavor, teaches Val- boroPro can enhance immune T-cell responses to reduce tumor growth in multiple mouse tumor models (Abstract): “ … Val- boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells … ” Walsh et al. teaches that Val- boroPro can lead to tumor regression when administered to solid tumors (Fig. 1 and 2). Walsh et al. further teaches (pg. 12): “ … our results demonstrate that the boronic dipeptide Val- boroPro induces T cell-mediated tumor rejection via a novel mechanism that involves accelerated T cell priming and enhanced DC trafficking … Val- boroPro represents a novel class of agent for boosting endogenous antitumor immune responses … ” Poplawski et al., in the same field of endeavor, teaches that Val- boroPro can be incorporated into an activatable form that is cleaved by proteases, including the (d)Ala-Pro substrate recognition sequence (Compound 5): Poplawski et al. teaches that Val- boroPro is a FAP inhibitor, and FAP inhibition has anticancer effects (Introduction): “ … 1 is a relatively nonspecific inhibitor of serine hydrolyses that cleave after proline, inhibiting other members of this group, which include FAP … FAP inhibition has been reported to yield anticancer effects … ” It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified the conjugate taught by the combined references of Bachovchin et al. and M ü ller et al. in view of Walsh et al. and Poplawski et al. to have exchange the protease inhibitor therapeutic moiety with Val- boroPro (i.e., the limitations of instant claims 32 and 33) with a reasonable expectation of success, as Poplawski et al. teaches that Val- boroPro can be conjugated to cleavable linkers such as (d)Ala-Pro. One would have been motivated to make this change to make a FAPα-activatable version of the FAPα inhibitor Val- boroPro to treat cancers such as solid tumors. Regarding the functional language “acutely toxic drug moiety” in instant claims 1 and 2, MCE is provided as an evidentiary reference to demonstrate that talabostat /Val- boroPro has acute oral toxicity (Section 2.1), meeting the claim limitations. Therefore, the invention as a whole was prima faci e obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. 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 . Claims 1-4, 6, 15, 16, 19, 20, 28, and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 9,597,410 (herein Pat ‘410) in view of Müller et al. ( MAbs . 2012 Nov-Dec;4(6):673-85. doi : 10.4161/mabs.22242, supra ), as evidenced by Bachovchin et al. (U.S. Patent 9,956,297, supra ). Pat ‘410 claims FAP-activated (i.e., “enzyme-cleavable”) proteasome inhibitors comprising a Ser-(d)Ala-Pro FAPα cleavable linker bound to a proteasome inhibitor (claim 3): Pat ‘410 additionally teaches methods of treating cancer comprising administration of the therapeutic (claim 22). Pat ‘410 does not teach the conjugates linked to half-life extension moiety . Müller et al., in the same field of endeavor, teaches that removal of the Fc domain or other half-life extending moieties in a therapeutic may pose issues when used to treat disease (Introduction): “ [t]he challenge being that the loss of the Fc domain and the reduction in size results in more rapid clearance of the molecules, which may be advantageous for diagnostic imaging, but is far from optimal for the treatment or management of chronic disease… ” Müller et al. teaches anti-HSA IgNAR binding domains that can be used to extend the serum half-life of therapeutics that it is conjugated to (Introduction): “ …we isolated a high affinity anti-HSA VNAR binding domain through immunization of a novel shark species… this is the first report of the use of this class of binding domain to affect in vivo retention by increasing the sera half-life of a fused domain… ” Müller et al. further teaches potential benefits of increasing the serum half-life of therapeutics (Introduction): “ [t] ailoring the half-life of therapeutic drugs would negate the requirement for multiple administrations, hence minimizing accumulative damage to the patient, increasing patient compliance and reducing the overall dosing regimen. Importantly, it would also open the opportunity to develop short-lived molecules, previously deemed unsuitable for drug development, into effective therapeutic agents. ” Müller et al. teaches that fusion of an anti-HSA IgNAR to another VNAR domain that does not bind a target increases that serum half-life (pg. 675): “ [t]o determine the efficacy of the anti-HSA VNAR domains to increase the serum half-life of another unrelated VNAR domain, fusions consisting of both N-terminally and C-terminally linked HSA-binding E06 to a random naïve VNAR domain known as 2V (sequence shown in Fig. 3B) were constructed… ”. The anti-HSA VNAR fusion constructs increased serum half-life by over 100-fold in mice when compared to the conjugate without the anti-HSA VNAR, and the serum half-life was over 150 hours in nonhuman primates (Table 2). Müller et al. further teaches (Discussion): “ [t]he lead clone isolated exhibited the ability to improve the PK parameters of a fused tandem VNAR domain exhibiting serum half-life values equating to that of albumin itself. This study provides the potential of these single binding domains to… act as tools to improve the PK properties of other biologic proteins. ” It would have been obvious to one of ordinary skill of the art, before the effective filing date of the instant application, to have modified the conjugate claimed by Pat ‘410 in view of Müller et al. to fuse the anti-HSA VNAR of Müller et al. to the FAPα activatable (i.e. “enzyme-cleavable”) protease inhibitor of Pat ‘410 (i.e., the limitations of instant claims 1 and 2) with a reasonable expectation of success, as Müller et al. teaches a method of conjugating the anti-HSA VNAR to other peptides, and the therapeutic claimed by Pat ‘410 has a peptide FAPα cleavable peptide moiety that can be fused to the anti-HSA VNAR (thus, the conjugate would have the anti-HSA VNAR conjugated to the protease inhibitor via the FAPα cleavage site). One would have been motivated to make this change to increase the half-life of the FAPα activatable protease inhibitor of Pat ‘410, which would reduce the frequency of administration and improve patient compliance and quality of life. The combined references do not teach the conjugate comprising a cell binding moiety. Regarding the functional limitation “acutely toxic” and the limitations of instant claim 28 , Bachovchin et al. is provided as an evidentiary reference to demonstrate that the proteasome inhibitors are acutely cytotoxic once activated (Col. 40, lines 44-46): “ …pro-drug version of a bortezomib-like cytotoxic agent designed to more selectively target the proteasome in