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 Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(a)-(d) and (f) or under 35 U.S.C. 120, 121, 365(a) or (b), or 386(a) is acknowledged. The present application is drawn from PCT/EP2022/060712, filed 4/22/2022; and claims benefit under 35 U.S.C. 119(a)-(d) to foreign application EP21170116.4, filed 4/23/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Status of Claims Claim s 1- 13 and 17-20 are pending and a re being examined on the merits. Claim Objections Claim FILLIN "Enter claim indentification information" \* MERGEFORMAT 9 is objected to because of the following informalities: Claim 9 recites “an electron to dense reagent”. As described in the specifications (pg. 3, line 9), the species of diagnostic agent is an “ electron-dense reagent” . Appropriate correction is required. Claim Rejections - 35 USC § 112 (b) 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. Claim s FILLIN "Enter claim indentification information" \* MERGEFORMAT 11, 13 and 19 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. Claim 11 recites wherein the therapeutically active moiety is selected for the group consisting of a monoclonal antibody or a fragment thereof, or derivatives thereof. A fragment of a monoclonal antibody may be considered to be a peptide with as few as any 2-3 amino acid residues. Does the claim encompass therapeutic moieties that are peptides comprising only 2 or 3 amino acid residues? Are such peptides considered members of the “group consisting of” the alternative species of therapeutic moieties? Further, claim 11 recites “or derivatives thereof.” It is unclear what species the derivatives are referring to; or what derivatives are encompassed. What is a derivative of an exosome, or what is a derivative of a CAR-T cell ? Without a clear understanding of the meaning of suitable fragments and/or derivatives, as they pertain to the various species of therapeutic moieties recited in the claims, the skilled artisan does not know the boundaries of the claim limitations. As the metes and bounds of the claim are unclear, claim 11 is rejected for indefiniteness. Claim 13 recites at least one moiety modulating pharmacokinetics is selected from the group consisting of an immunoglobulin or immunoglobulin fragment , or an unstructured amino acid sequence comprising amino acids alanine, glycine, serine and proline. An immunoglobulin fragment may be interpreted as a peptide consisting of as few as 2-3 amino acid residues, in which case it is unclear what relevance it has to being an immunoglobulin, or what 2-3 amino acid peptides are encompassed by the claim limitations. Regarding “an unstructured amino acid sequence comprising amino acids alanine, glycine, serine and proline”; the claim seems to be drawn to a coupling domain (e.g. a linker), as described in the specifications (pg. 14 lines 1-25 and again as a pharmacokinetic moiety pg. 15, lines 24-36). However, it is unclear whether any peptide comprising an alanine, glycine, serine or proline is encompassed; and if so, what the claim is limited to. Further, the claim recites wherein the unstructured sequence comprises alanine, glycine, serine and proline. Thus, as written, the unstructured sequence must comprise at least one of each of an alanine, glycine, serine and proline. Thus, a glycine/serine (G 4 S) linker, for example, is not encompassed by the unstructured sequence as claimed. Thus, it is unclear to the skilled artisan what unstructured sequences, or immunoglobulin fragments, are encompassed by the claims, and what is not. For example, if the claim limitations were drawn to a “half-life extending moiety, ” which may encompass a wide range of structures, fragments and/or sequences known in the art , it is clear to the artisan what the boundaries of the claim limitations are. As “fragments” and “unstructured sequences” are unclear, the metes and bounds of the claim are unclear and claim 13 is rejected for indefiniteness. Regarding claim FILLIN "Enter claim identification information" \* MERGEFORMAT 19 , the phrase " optionally " renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). It is unclear if the infectious diseases are limited to chronic viral infections or encompass any infectious disease. 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. Claims FILLIN "Enter claim identification information" \* MERGEFORMAT 1-13 and 17-20 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 following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions: The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice... reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly , 119 F.3d at 1568, 43 USPQ2d at 1406. 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. Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed. Independent claim 1 recites an anti-PD-L1 binding protein comprising an amino acid sequence having at least 90% identity to any one of SEQ ID NOs: 1-20. The proteins of SEQ ID NOs: 1-20 comprise Affilin ® proteins (specs., pg. 1, line 8), which are derived from a wildtype ubiquitin sequence (pg. 4, lines 13-19; Figure 1). Figure 1 depicts the 76 amino acid sequence of ubiquitin from which the anti-PD-L1 binding proteins are derived. For reference, SEQ ID NOs: 1-6 are all between 76-84 amino acids in total length; thus supporting that the 76 amino acid ubiquitin sequence provides the “scaffold” from which the proteins of the invention were derived, and which provides a significant structural basis of the proteins of the invention. A sequence having “at least 90% identity” to a sequence that is 76 amino acids in length allows for up to 7 amino acid residue substitutions; most of SEQ ID NOs: 1-20 have more than 76 amino acids, which would allow for greater than 7 amino acid substitutions in those embodiments. Note that SEQ ID NO s : 7 -9 and 17-20 are multimers of SEQ ID NOs: 10-16 (see Table 1, pg. 13); therefore the 13 sequences of Figure 1 (SEQ ID NOs: 1-6 and 10-16) are the representative sequences of SEQ ID NOs: 1-20 . Nonetheless, there is no teaching of which amino acid residues may be mutated, or which amino acids may be substituted in at any given residue. Therefore, the claims encompass a genus of binding proteins, which may have at least 7 amino acid mutations. Simultaneous randomized substitution of 20 different amino acids at 7 different residues encompasses at least 20 7 different embodiments. Thus, claim 1 is drawn to a genus of (at least) 20 7 different, unidentified, protein sequences which bind to PD-L1 with a binding affinity of at least 250 nM , and which inhibits the interaction of PD-L1 with PD1. Protein chemistry is probably one of the most unpredictable areas of biotechnology. It is known in the art that the relationship between the amino acid sequence of a protein (polypeptide) and its tertiary structure (i.e. its binding activity) are not well understood and are not predictable (see Ngo et al., in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz, et al., (ed.), Birkhauser , Boston, MA, pp. 433 and 492-495). There is no recognition in the art that partial sequence identity predicts biological function. It is known in the art that even a single amino acid change or differences in a protein's amino acid sequence can have dramatic effects on the protein's function. For example, conservative replacement of a single “lysine” reside at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein ( Burgess et al., J of Cell Bio. 111:2129-2138, 1990). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen ( Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988). These references demonstrate that even a single amino acid substitution or what appears to be an inconsequential chemical modification will often dramatically affect the biological activity and characteristic of a protein. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with reasonable expec tation of success are limited. Certain positions in the sequence are critical to the three-dimensional structure/function relationship, and these regions can tolerate only conservative substitutions or no substitutions. Residues that are directly involved in protein functions such as binding will certainly be among the most conserved ( Bowie et al. Science, 247:1306-1310, 1990, p. 1306, col.2). This i s f urther exempli fied , in the case of antibody design, in the Court decision in Abbvie ( Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions and which bound the target, but in no way allowed one to envisage the unique structure of Centocor’s antibodies which bound the same target but shared only 50% sequence similarity. Thus, when claiming a genus of proteins based on their binding to a common target, the representative examples must cover the full scope of structural variabilities which encompass all species variants that would bind the target. In support of the claimed genus of anti-PD-L1 binding proteins with at least 90% sequences identity to any of SEQ ID NOs: 1-20 the specifications disclose 13 embodiments, of SEQ ID NOs: 1-6 and 10-16 (Figure 1) . However, while the examples teach the mutations from the base ubiquitin sequence to get to the 13 embodiments, the examples do not teach which amino acid residues may be mutated in any of the 13 embodiments to generate further variants with >90% identity, or which amino acids may be substituted at any specific residue. Thus, the representative examples of the specifications do not teach which structural aspects may be altered. For example US Patent 10,858,405 teaches EGFR binding molecules based on ubiquitin mutants ( Affilin ®; abstract); including SEQ ID NO: 66 ( affilin 140077; col. 85; col. 128, claim 5). Patent ‘405 SEQ ID NO: 66 comprises instant SEQ ID NO: 14 with 92% sequence identity; only 5 amino acid residues are substituted. However, Patent ‘405 SEQ ID NO: 66 is drawn to an EGFR binding protein, and not a PD-L1 binding protein. Thus, the art demonstrates similar ubiquitin-derived binding proteins that have >90% sequence identity to instant SEQ ID NO: 14, yet bind an entirely different target. While the specifications disclose methods for screening binders using the phage display library (specs., pg. 19, Example 1) , it does not provide sufficient written description support as to the structures of all binders isolated from the screening the library . It is duly noted that the written description provision of 35 U.S.C. 112 is severable from its enablement provision. “The purpose of the written description requirement is broader than to merely explain how to ‘make and use;’ the 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.” MPEP section 2161. Section 2163(II)(A)(3)(a)(ii) of the MPEP states that the written description for a claimed genus may be satisfied through either a) a representative number of species, or b) disclosed correlation between function and structure. Here the applicants do not provide any variants of the selected species of SEQ ID NOs: 1-6 and 10-16 , in which mutations were made, which were reduced to practice . Applicants also do not identify the shared structural properties that would define the genus beyond the desired functionality ; currently the essential property of binding PD-L1 is imparted by the specific set of binding protein sequences that have been reduced to practice. Specifically, the physical features (or amino acid residues encoding said features) which impart the property of binding PD-L1 with a binding affinity of at least 250 nM , wherein the protein inhibits interaction of PD-L1 with PD-1, should be disclosed. Further, a description of the type and number of amino acid residue substitutions that may be made at such identified positions within the sequence, that result in “at least 90 %” sequence identity to a selected sequence, would be essential in determining the degree of variability that may be allotted in total sequence identity. This lack of definition complicates the determination of the boundaries of the claimed genus with regard to which, as of yet unidentified, species variants ( proteins with >90% sequence identity ) would be anticipated, a priori , by one skilled in the art, to fall within the scope of the claims. Without the identification of the necessary shared structural properties of all species variants that fall within the scope of the genus, it may be th at a generic protein sequence with < 90 % sequence identity would still bind PD-L1 with greater than 250 nM affinity , or conversely, that proteins with > 90 % sequence identity (such as Patent ‘405 SEQ ID NO: 66 ) would not bind PD-L1 . In view of this uncertainty , the lack of a representative number of examples of the claimed genus , and the lack of description of the necessary shared structural features which impart the desired functionality , claim 1 is rejected for lack of adequate written description support. Claims 2-13 and 17-20 are also rejected as they are dependent on rejected claim 1 but fail to rectify the lack of descriptive support . Allowable Subject Matter SEQ ID NOs: 1-20, of independent claim 1, have been searched and are free of the prior art of proteins comprising any of SEQ ID NOs: 1-20 with 100% sequence identity . Art of Interest Application 18/575,743, with common inventor Mathias Kahl, recites a protein of SEQ ID NO: 10 (claim 4), which has 100% sequence identity to instant SEQ ID NO: 10. However, the claims of application ‘743 are drawn to an affinity ligand that has a binding affinity of less than 100 nM for a ubiquitin mutein of SEQ ID NO s: 10-19 (claim 4). Double Patenting was considered, but the scope of the invention of application ‘743 is different from the instant application. Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JAMES R. MELCHIOR whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-4761 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8:00-5:00 CST . 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 Samira Jean-Louis can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 270-3503 . 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. /JAMES RYLAND MELCHIOR/ Examiner, Art Unit 1644 /NELSON B MOSELEY II/ Primary Examiner, Art Unit 1642