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 Application, Amendments and/or Claims The amendment, filed 26 January 2023, has been entered in full. The amendment, filed 19 July 2023, has been entered in full. Claims 2 , 7, 11, 14, 16-20, 23-26, 29, 31-35, 38-45, 47, 49-60 are canceled. Claims 3-6, 8, 12, 13, 15, 21, 27, 28, 30, 36, 37, 46 and 48 are amended. Applicant’s election of Group I ( claims 1, 3-6, 8-10, 12, 13, 15, 21, 22, 27 and 36, drawn to a polypeptide that binds to human serum albumin (HSA) with a Kd of 1 x10-6 M or less at pH 7.4 and at pH 6 binds to HSA with a Kd that is at least half a log less than the Kd for binding to HSA at pH 7.4 and a pharmaceutical composition comprising the polypeptide ) and the species election of species (d), including SEQ ID NOs: 116, 114, 113, 111 and 110, in the reply filed on 18 February 2026 is acknowledged. The Examiner has added the species of SEQ ID Nos: 112, 115 and 138. Because A pplicant 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)). Claims 28, 30, 37, 46 and 48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 18 February 2026. Claims 1, 3-6, 8-10, 12, 13, 15, 21, 22 and 27 are under examination. Information Disclosure Statement The information disclosure statement(s) (IDS) (filed 2/19/2026 and 4/26/2023 ) w ere received and compl y with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. They have been placed in the application file and the information referred to therein has been considered as to the merits. Specification The disclosure is objected to because of the following informalities: The instant specification recites “7A” and “”7B” (see para 0225), but the Brief Description of Drawings only teaches Figure 7. Appropriate correction is required. 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 s 1, 3-6, 8-10, 12, 13, 15, 21, 27 and 36 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 claim(s) contains 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 inventor(s), at the time the application was filed, had possession of the claimed invention. The instant specification teaches recombinantly engineered variant s of stefin polypeptides ( a.k.a. AFFIMER polypeptides) that bind to human serum albumin and extends the half-life of the polypeptides (abstract). The affimer polypeptide is b ased on naturally occurring proteins (cystatins) that have been engineered to stably display two loops that create a binding surface . T he serum albumin-binding AFFIMER polypeptides of the present disclosure provide a number of advantages over antibodies, antibody fragments, and other non-antibody molecule-binding proteins. One is the small size of the AFFIMER polypeptide itself. In its monomeric form it is about 14 kDa , or 1/10th the size of an antibody. This small size gives greater potential for increased tissue penetration, particularly in poorly vascularized and/or fibrotic target tissues (like tumors). The specification teaches AFFIMER polypeptides have a simple protein structure (versus multi-domain antibodies) and as the AFFIMER polypeptides do not require disulfide bonds or other post-translational modifications for function, these polypeptides can be manufactured in prokaryotic and eukaryotic systems (para 0103) . The specification teaches that AFFIMER polypeptides display two peptide loops and an N-terminal sequence that can all be randomized to bind to desired target proteins with high affinity and specificity, in a similar manner to monoclonal antibodies. These engineered non-antibody binding proteins are designed to mimic the molecular recognition characteristics of monoclonal antibodies in different applications. (para 0109). The specification teaches anti-HSA AFFIMER polypeptides comprise an AFFIMER polypeptide in which at least one of the solvent accessible loops is from the wild-type stefin A protein having amino acid sequences to enable an AFFIMER polypeptide to bind HSA, selectively, and in some embodiments, with K.sub.d of 10.sup.− 6M or less (para 0111) The claimed subject matter is not supported by an adequate written description for the following reasons. A “polypeptide that binds to human serum albumin (HSA) with a Kd of 1x10-6 M or less at pH 7.4, and at pH 6 binds to HSA with a Kd that is at least half a log less than the Kd for binding to HSA at pH 7.4 ” is required to practice the claimed invention . The instant polypeptide must further have the biological function of “ a serum half-life in human patients of greater than 10 hours ” and “ a serum half-life in human patients of greater than 50% of the serum half-life of HSA” . The broadest claims read on a polypeptide sequence having any number of amino acid residue substitutions, deletions and/or insertions at every position with respect to the wild-type sequence as long as it retains function. There is not upper limit to the number of alterations that can be permitted in the claimed polypeptides as long as they have the desired activity. The other claims recite less than 100% identity, which can encompass 10% of amino acid residue deletions, substitutions and/or additions across the sequence . Accordingly , the instant claims are drawn to a genus of polypeptides that have functional limitations, but no structural limitations. The number of structures encompassed by the genus may be vast or conversely there may be no structures that possess the claimed function. MPEP§ 2163 states : t he written description requirement for a claimed genus may be satisfied through establishment of a structure-function correlation (show a structure is correlated with the function) OR through a sufficient description of a representative number of species (show a representative number of species that have the function. There must be enough species that are representative of the full breadth of the genus). Regarding structure-function correlation: The scientific art teaches that the problem of predicting protein structure and in turn utilizing predicted structural determinations to ascertain functional aspects of the protein is extremely complex. It is in no way predictable that randomly selected changes in the disclosed sequence would afford a protein having activity comparable to the one disclosed. For sequences having one or two substitutions, for example, the artisan would reasonably expect that many of the possible variants would retain functional properties comparable to those of the unmodified protein, and it would require only routine manipulations to make and test a reasonably representative sampling of the possible variants. However, as the number of modified sites increases, the number of possible variants, and hence the degree of experimentation required, increases exponentially. Additionally, as plural substitutions are introduced, their interactions with each other and their effects on the structure and function of the protein become progressively less predictable. Even if the instant specification outlined art-recognized procedures for producing and screening for active muteins, this is not adequate guidance as to the nature of active derivatives that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation. The ordinary artisan would immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active; conformation is dependent upon surrounding residues. Substitution of non-essential residues can often destroy activity For example, Fenton et al. state that while it is well known that most substitutions at conserved amino acid positions (which they call “toggle” switches) abolish function, it is also true that substitutions at non-conserved positions (which they call “rheostat” positions) are equally capable of affecting protein function. They conclude that substitutions at rheostat positions have highly unpredictable outcomes on the activities and specificities of protein-based drugs (see entire reference)( Rheostat positions: A new classification of protein positions relevant to pharmacogenomics Medicinal Chemistry Research 29:1133-1146; 2020). Bhattacharya et al. state that the range of possible effects of even single nucleotide variations at the protein level are significantly greater than currently assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge (p. 18)( Impact of genetic variation on three - dimensional structure and function of proteins PLoS ONE 12(3): e0171355; 2017). See also Tokuriki et al. (Stability effects of mutations and protein evolvability, Current Opinion in Structural Biology, 19:596-604, 2009). In addition, when multiple mutations are introduced, there is even less predictability. As the number of modified sites increases, the number of possible variants, and hence the degree of experimentation required, increases exponentially. As plural substitutions are introduced, their interactions with each other and their effects on the structure and function of the protein become progressively less predictable. For evidence thereof, see Guo et al., who state that the effects of mutations on protein function are largely additive (page 9207, left column, full paragraph 2)( Guo et al. Protein tolerance to random amino acid change. PNAS USA 101(25):9205-10; 2004). While the claimed human serum albumin binding polypeptide is not an antibody, the specification teaches that the instant polypeptide must still bind to desired target proteins with high affinity and specificity, in a similar manner to monoclonal antibodies. The art recognizes that the formation of an intact antigen-binding site of all antibodies requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (see entire reference)( Al Qaraghuli et al. Antibody ‑ protein binding and conformational changes: identifying allosteric signaling pathways to engineer a better effector response. Nature Scientific Reports 10:13969, 2020). Rudikoff et al. provides an example of how even a conservative change to a single amino acid residue in a CDR region binding site of an antibody can ablate antigen binding (see, for example, Abstract) (Single amino acid substitution altering antigen-binding specificity Proc. Natl. Acad. Sci. USA, 79: 1979-1983, March 1982). The state of the art evidences the unpredictability of the effects of mutation s on p olypeptides structure and function. There is a lack of structure-function correlation in polypeptide molecules . Regarding a representative number of species: the instant specification fails to describe a representative number of species to provide adequate written description of the claimed genus as per MPEP § 2163. There must be enough species that are representative of the full breadth of the genus. The instant specification teaches 7 species of polypeptides which bind human serum albumin (HSA) at pH 7.4. with a Kd less than 1 x 10-6M (Table 4). The Examiner does not see wherein the instant polypeptides bind HSA at a pH of 6.0 with a Kd that is at least one log less than the Kd for binding to HSA at pH 7.4. For example, the specification at Table 4 teaches HSA-18 (SEQ ID NO: 110) has a Kd of 36.1 nM at a pH of 7.4. A n entire log less than 36.1 nM would be 3.61 nM. Besides HSA-22 (SEQ ID NO:112), the Examiner does not see wherein the instant polypeptides bind HSA at a pH of 6.0 with a Kd that is at least ½ log less than the Kd for binding to HSA at pH 7.4. At any rate, a disclosure of 7 species with some of said species having the claimed biological function, is not representative of an entire genus of polypeptides comprising an unlimited number of amino acid residue insertions, substitutions and/or deletions, while having the associated biological function of binding to human serum albumin (HSA) with a Kd of 1x10-6 M or less at pH 7.4 AND at pH 6 binding to HSA with a Kd that is at least half a log (or one log) less than the Kd for binding to HSA at pH 7.4 AND having a serum half-life in human patients of greater than 10 hours AND having a serum half-life in human patients of greater than 50% of the serum half-life of HSA. The disclosed species is not representative of the genus because the genus is highly variant and encompasses an unlimited number of individual and combination changes . T he instant specification fails to describe a sufficient variety of species to reflect the variation within the genus. There must be enough species that are representative of the full breadth of the genus . The claims depend on a recited property, where the claim covers every conceivable structure for achieving the stated property, while the instant specification fails to describe any species with sufficient identifying characteristics such that one skill in the art could visualize or recognize the identity of the claimed subject matter. The level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which of those molecules have the claimed activity . Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, the full breadth of the claims do not meet the written description provision of 35 U.S.C. §112, first paragraph. Claim Rejections - 35 USC § 102 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 1, 4, 5 and 36 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhong et al. (US 2021/0230242; published July 29, 2021, priority date June 18, 2018). Zhong et al. teach the Kd of anti-HSA antibodies that bind human serum albumin (HSA) at pH 7.4. Zhong et al. teach that Table 9 shows the calculated Kd of three different anti-HSA antibodies at pH 7.4. Zhong et al. teach the anti-HSA antibody (i.e. polypeptide) binds to human serum albumin (HSA) with less than Kd of 1 x 10-6M at pH 7.4 (para 0555 and Table 9)( applies to claim 1 ). Chemical compounds and their properties are inseparable (In re Papesch , 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh , 362 F.2d 821, 150 USPQ 300 (CCPA 1966)). Therefore, the anti-HSA antibody which binds human serum albumin at pH 7.4. with a Kd less than 1 x 10-6M, as taught by Zhong et al., would have the functional properties of having a serum half-life in human patients of greater than 10 hours and a serum half-life in human patients of greater than 50% of the serum half-life of HSA ( applies to claims 4 and 5 ). Zhong et al. teach pharmaceutical compositions comprising the anti-HSA antibody (paras 10, 17, 116- 117)( applies to claims 36 ). Claims 1, 6, 9, 10 and 36 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Basran et al. (Reference submitted by Applicant; US 2021/0163599; published June 3, 2021, priority date April 11, 2018) The applied reference has a common Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. Basran et al. teach a polypeptide wherein the amino acid sequence is represented in general formula III (i.e. SEQ ID NO: 167)( para 274)( applies to claims 6, 9 and 10 ). Because claims 6, 9 and 10 depend and further limit claim 1. The polypeptide would have the biological function of binding to human serum albumin (HSA) with a Kd of 1x10-6 M or less at pH 7.4, and at pH 6 binds to HSA with a Kd that is at least half a log less than the Kd for binding to HSA at pH 7.4 ( applies to claim 1 ). Basran et al. teach pharmaceutical compositions suitable for therapeutic use in a human patient comprising the polypeptide and a pharmaceutically acceptable carrier (paras 0009, 0097, 0209, 0255-0256, 0263 and 0274)( applies to claim 36 ). Allowable Subject Matter Claim objection A sequence search has revealed no prior art for SEQ ID Nos: 110-116 and 138. Claim 22 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims . Conclusions Claims 1, 3-6, 8-10, 12, 13, 15, 21, 27 and 36 are rejected. Claim 22 is objected to . No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT REGINA M DEBERRY whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0882 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9:00-6:30 pm (alt Fri) . 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, FILLIN "SPE Name?" \* MERGEFORMAT Joanne Hama can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 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. /R. M.D / Examiner, Art Unit 1647 3/ 30 /2026 /JOANNE HAMA/ Supervisory Patent Examiner, Art Unit 1647