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 of 31 March 2023 has been entered in full. Claims 1, 3-5, 11-13, 15-23 are amended. Claims 6-10 and 14 are cancelled. Claims 24 and 25 are added. Claims 1-5, 11-13, and 15-25 are under consideration in the instant application. Priority Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Information Disclosure Statement The information disclosure statements (IDS) submitted on 26 February 2026; 27 March 2024; 01 August 2023; and 31 March 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Drawings 1. The drawings are objected to for the following reasons: 1a . The instant drawings do not comply with 37 C.F.R. § 1.84(U)(1), which states that partial views of a drawing which are intended to form one complete view, whether contained on one or several sheets, must be identified by the same number followed by a capital letter. Figure 1 of the instant application, for example, is presented on 5 separate panels/pages. The five total sheets of drawings for Figure 1 should be renumbered ''Figures 1A-1 E ”. 1b . Furthermore, in Figure 1, the amino acid substitutions that are bolded are extremely difficult to discern from the amino acids in the rest of the sequence . The bolded amino acids also may not be reproduced if the case issues into a patent . It is suggested that the substitutions are further underlined or starred . Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance. Applicant is reminded that once the drawings are changed to meet the separate numbering requirement of 37 C.F.R. 1 1.84(U)(1), Applicant is required to file an amendment to change the Brief Description of the Drawings and the rest of the specification accordingly. Nucleotide and/or Amino Acid Sequence Disclosures REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES Items 1) and 2) provide general guidance related to requirements for sequence disclosures. 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted: In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying: the name of the ASCII text file; ii) the date of creation; and iii) the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying: the name of the ASCII text file; the date of creation; and the size of the ASCII text file in bytes; In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended). When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical. If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical. Specific deficiencies and the required response to this Office Action are as follows: 2. Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Specifically, the incorporation by reference paragraph does not identify the size of the text file in bytes . Rather, the paragraph indicates that the file is 49 KB (kilobytes). 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 incorporation-by-reference paragraph, 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 3. The disclosure is objected to because of the following informalities: 3a. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 64, line 18; page 65, lines 8 and 18 ) . 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. 3b. The Brief Description of the Drawings does not refer to Figures 3A, 3B, 4A, 4B, 6D, and 6E. 3c. The Brief Description of the Drawings for Figure 1 is not descriptive (see MPEP §608.01(f)). At page 8, line 33, the specification simply states, “Amino acid sequences”. The Brief Description should be amended to provide more detail as to what the sequences are and/or what specific features are included. 3d. The specification refers to “claims 1 to 3 ” at page 7, line 23 . Reference to claims 1 -3 should be deleted from the body of the specification because if the case is ever allowed and issues into a patent, the claim numbering is subject to change. Claim Objections 4. Claim s 1-5, 11-13, and 19 are ob jected to because o f the following informalities: 4a. Claims 1 -5, 11-13, and 19 recite the acronym “ oxMIF ” without first defining what it represents. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim. 4b. In claim 13, line 3, after the phrase “Fab’,”, the word “and” is extraneous and should be deleted. 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. 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. 5. Claim 2 is 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. 5a. Claim 2 is rejected as being indefinite because the claim references amino acid substitutions without reciting the specific variable domain (s) in which the substitutions are to be made. Claim 1, from which claim 2 depends, recites a light chain variable domain (SEQ ID NO: 9) and a heavy chain variable domain (SEQ ID NO: 6). Claim 1 recites specific and non-specific amino acid substitutions in both domains. Since the amino acid sequences of SEQ ID NOs: 6 and 9 are both larger than 100 amino acids in length, it is not clear which variable domains have substitutions W93F and/or W97Y introduced, as required by claim 2. For example, are the substitutions made in the light chain variable region only? The heavy chain variable region only? Is W93F in the light chain variable region and/or W97Y in the heavy chain variable region? Or, is W97Y in the light chain variable region and W93F in the heavy chain variable region? Claim Rejections - 35 USC § 112(a) 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. Written Description 6. Claim s 1-3, 13, and 15-25 are rejected und er 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. Claim 1, for example, is directed to a recombinant anti- oxMIF antibody or an antigen binding fragment thereof having reduced aggregation potential and reduced hydrophobicity, comprising the following variable domain s: (a) a light chain variable domain, wherein the light chain variable domain comprises: (i) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, or ( ii ) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with 1, 2, 3, 4, or 5 further amino acid substitutions, with the proviso that the tyrosine at position 36 is preserved; and (b) a heavy chain variable domain, wherein the heavy chain variable domain comprises: (i) SEQ ID NO: 6, (ii) SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, or (iii) SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with 1, 2, 3, 4 or 5 further amino acid substitutions, wherein amino acid positions are numbered according to Kabat, and wherein aggregation potential and hydrophobicity are reduced compared to an antibody or an antigen binding fragment thereof comprising SEQ ID NO: 6 and SEQ ID NO: 9 lacking the amino acid substitutions. The specification of the instant application teaches that it is the objective of the invention to improve antibodies or antigen binding fragment thereof targeting oxMIF (oxidized MIF) and having reduced aggregation propensity and hydrophobicity. The specification teaches that a functional variant may comprise a substitution, deletion and/or addition of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid residues, or a combination thereof, which substitutions, deletions and/or additions are conservative modifications and do not alter the antigen binding properties (page 19, lines 13-16). The specification continues to teaches that a functional variant as described herein comprises no more than or up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions, deletions and/or additions, which are conservative modifications and do not alter the antibody's function and that a functionally active variant as described herein comprises up to 15, preferably up to 10 or 5, amino acid substitutions, deletions and/or additions, which are conservative modifications and do not alter the antibody's function (page 19, lines 16-22). The examples of the specification disclose newly designed oxMIF antibodies with specific VH substitutions (L5Q, W97Y in SEQ ID NO: 6) and VL substitutions (M30L, F49Y, A51G, P80S, W93F in SEQ ID NO: 9) and combinations thereof (pages 42-43, Table 1). The specification teaches that the new antibodies bind soluble oxMIF and have reduced aggregation and hydrophobicity (Examples 1-2 , 8 ). Therefore, in view of the instant specification and claims, one alternative for the anti- oxMIF antibody light chain variable domain comprises SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with 1, 2, 3, 4, or 5 further amino acid substitutions , with the proviso that the tyrosine at position 36 is preserved . An additional alternative for the anti- oxMIF heavy chain variable domain comprises SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with 1, 2, 3, 4 or 5 further amino acid substitutions . However, the specification does not teach any further variant s/substitutions of the light and heavy chain variable region amino sequences other than the full-length amino acid sequences of SEQ ID NOs: 9 and 6, respectively or SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F ; and SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y . The first paragraph of 35 U.S.C. § 112 "requires a 'written description of the invention' which is separate and distinct from the enablement requirement." Vas-Cath Inc. v. Mahurkar , 935 F.2d 1555, 1563 (Fed. Cir. 1991). An adequate written description of a chemical invention "requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004); Regents of the Univ. of Cal. v. Eli Lilly & Co., Inc., 119 F.3d 1559, 1566 (Fed. Cir. 1997); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993). "A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F.3d at 923; Eli Lilly, 119 F.3d at 1568. Instead, the "disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described." Id. In addition, possession of a genus "may be achieved by means of a recitation of a representative number of [compounds] ... falling within the scope of the genus." Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 F.3d at 927. Thus, case law dictates that to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include actual reduction to practice, disclosure of drawings or structure chemical formulas, sufficient relevant identifying characteristics (such as, complete or partial structure, physical and/or chemical properties, and functional characteristics when coupled with a known or disclosed structure/function correlation), methods of making the claimed product, level of skill and knowledge in the art, predictability in the art, or any combination thereof. In the instant case, one factor present in the claims is a structural characteristic of an anti- oxMIF antibody comprising light chain and heavy chain variable domains, wherein the light chain variable domain comprises SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with 1, 2, 3, 4, or 5 further amino acid substitutions , with the proviso that the tyrosine at position 36 is preserved ; and wherein the heavy chain variable domain comprises SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with 1, 2, 3, 4 or 5 further amino acid substitutions . An additional factor present in the claims is a functional requirement that the anti- oxMIF antibody has reduced aggregation potential and reduced hydrophobicity. There is no identification of any particular sequence or structure of the antibody that must be conserved in order to provide the required functions of having reduced aggregation potential and reduced hydrophobicity (other than a light chain variable domain comprising SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and a heavy chain variable domain comprising SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y ) . Thus, the claims are drawn to a genus of anti- oxMIF antibodies that comprise light/heavy chain variable region sequence variants with any 1, 2, 3, 4, or 5 further amino acid substitutions (and polynucleotides encoding such). In this case, the specification fails to disclose and there is no art-recognized correlation between the structure of the genus of variant antibodies and polynucleotides encoding such and the functions of having reduced aggregation potential and reduced hydrophobicity . In other words, the specification does not teach the structure which results in an antibody with the claimed required characteristics. The description of newly designed oxMIF antibodies with specific VH substitutions (L5Q, W97Y in SEQ ID NO: 6) and VL substitutions (M30L, F49Y, A51G, P80S, W93F in SEQ ID NO: 9) and combinations thereof (pages 42-43, Table 1) are not adequate written description of an entire genus of anti- oxMIF antibodies that comprise a light chain variable domain comprising SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with any 1, 2, 3, 4, or 5 further amino acid substitutions , with the proviso that the tyrosine at position 36 is preserved ; and a heavy chain variable domain comprising SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with any 1, 2, 3, 4 or 5 further amino acid substitutions (and polynucleotides encoding such) that have reduced aggregation potential and reduced hydrophobicity . The art recognizes that protein function cannot be predicted from structure alone (Bork, 2000, Genome Research 10:398-400; Skolnick et al., 2000, Trends in Biotech. 18(1):34-39, especially p. 36 at Box 2; Doerks et al., 1998, Trends in Genetics 14:248-250; Smith et al., 1997, Nature Biotechnology 15:1222-1223; Brenner, 1999, Trends in Genetics 15:132-133; Bork et al., 1996, Trends in Genetics 12:425-427). See also Tokuriki et al. (Current Opinion in Structural Biology 19: 596-604, 2009), who teach that mutations are generally destabilizing. For instance, Tokuriki et al. teach at page 596, right column, last paragraph, that “as mutations accumulate, protein fitness declines exponentially...or even more than exponentially...So by the time an average protein accumulates, on average, five mutations, its fitness will decline to <20%.” Further, at page 598, left column, last paragraph, Tokuriki et al. note that 50% of mutations are destabilizing, and >15% of mutations are highly destabilizing, and of the about 5% of mutations that are stabilizing values...many of these mutations result in inactive protein. Fenton et al. (Medicinal Chemistry Research 29:1133-1146, 2020) also 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 nonconserved 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. Bhattacharya et al. ( PLoS ONE 12(3): e0171355, 2017) 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). Furthermore, it is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, William E., Fundamental Immunology, 3rd Edition, Raven Press, New York, Chapt . 8, pp. 292-295 (1993), under the heading “ Fv Structure and Diversity in Three Dimensions”). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA. Vol 79, page 1979, 1982 ; cited on the IDS of 26 February 2026 ) and Zhang et al. ( mAbs 7(1): 42-52, 2005; page 45, column 2)). Zhang et al. also indicate that minor variations in variable heavy and light chain CDR1s and CDR2s may lead to loss of antigen binding (page 46, column 1). It is noted that numerous other publications also acknowledge that conservative substitutions would in fact change the binding ability of antibodies, if not substantially reduce the affinity (see Vasudevan et al., Blood Cell Mol Dis 32: 176-181, 2004;; Brummell et al, Biochemistry 32: 1180-1187, 1993;; Kobayashi et al., Protein Engineering 12: 879-844, 1999;; Burks et al., PNAS 94: 412-417, 1997;; Jang et al., Mol Immunol 35: 1207-1217, 1998; Brorson et al. J Immunol 163: 6694-6701, 1999;; Colman, Res Immunol 145: 33-36, 1994;; Casset et al. Biochem Biophys Res Comm 307: 198-205, 2003;; Holm et al. Mol Immunol 44: 1075-1084, 2007). Thus, the state of the art recognized that it would be highly unpredictable that an antibody that binds oxMIF with light and heavy chain variable region s with any 1, 2, 3, 4, or 5 further amino acid substitutions as recited in the instant claims, would maintain its required conformation and would have the requisite antigen binding function. Applicant is reminded that generally, 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 ( Enzo Biochem , Inc . v. Gen-Probe Inc ., 323 F.3d 956 (Fed. Cir. 2002) ; Noelle v. Lederman , 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co ., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi , 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” ( Amgen page 1361). Vas-Cath Inc. v. Mahurkar , 19USPQ2d 1111, clearly states 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). See also, Amgen Inc. v. Sanofi , 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co ., 94 USPQ2d 1161 (Fed Cir. 2010). 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). A “mere wish or plan” to obtain the claimed invention is not sufficient ( Centocor Orth Biotech, Inc. v. Abbott Labs , 636 F.3d 1341 (Fed. Cir. 2011); Regents of the Univ. of California , 119 F.3d at 1566). In the instant application, the skilled artisan cannot envision the detailed chemical structure of the antibody variants (and polynucleotides encoding such) of the encompassed claims, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. 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 antibody (and polynucleotide encoding such) is required. See Fiers v. Revel , 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. , 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird , 30 USPQ2d 1481 at 1483. 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, only a recombinant anti- oxMIF antibody or antigen binding fragment comprising (a) a light chain variable domain, wherein the light chain variable domain comprises: (i) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F ; and (b) a heavy chain variable domain, wherein the heavy chain variable domain comprises: (i) SEQ ID NO: 6, or (ii) SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, but not the full breadth of the claims meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). See also Ariad Pharm., Inc. v. Eli Lilly & Co. , 598 F.3d 1336, 1355 (Fed. Cir. 2010). Scope of Enablement 7. Claim s 1-3, 13, and 15-25 are 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 recombinant anti- oxMIF antibody or antigen binding fragment comprising (a) a light chain variable domain, wherein the light chain variable domain comprises: (i) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F ; and (b) a heavy chain variable domain, wherein the heavy chain variable domain comprises: (i) SEQ ID NO: 6, or (ii) SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, does not reasonably provide enablement for an anti- oxMIF antibody comprising light and heavy chain variable domains, wherein the light chain variable domain comprises (i) SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with 1, 2, 3, 4, or 5 further amino acid substitutions , with the proviso that the tyrosine at position 36 is preserved ; and (ii) wherein the heavy chain variable domain comprises SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with 1, 2, 3, 4 or 5 further amino acid substitutions . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. Claim 1, for example, is directed to a recombinant anti- oxMIF antibody or an antigen binding fragment thereof having reduced aggregation potential and reduced hydrophobicity, comprising the following variable domains: (a) a light chain variable domain, wherein the light chain variable domain comprises: (i) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, or ( ii ) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with 1, 2, 3, 4, or 5 further amino acid substitutions, with the proviso that the tyrosine at position 36 is preserved; and (b) a heavy chain variable domain, wherein the heavy chain variable domain comprises: (i) SEQ ID NO: 6, (ii) SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, or (iii) SEQ ID NO:6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with 1, 2, 3, 4 or 5 further amino acid substitutions, wherein amino acid positions are numbered according to Kabat, and wherein aggregation potential and hydrophobicity are reduced compared to an antibody or an antigen binding fragment thereof comprising SEQ ID NO: 6 and SEQ ID NO: 9 lacking the amino acid substitutions. The specification of the instant application teaches that it is the objective of the invention to improve antibodies or antigen binding fragment thereof targeting oxMIF (oxidized MIF) and having reduced aggregation propensity and hydrophobicity. The specification teaches that a functional variant may comprise a substitution, deletion and/or addition of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid residues, or a combination thereof, which substitutions, deletions and/or additions are conservative modifications and do not alter the antigen binding properties (page 19, lines 13-16). The specification continues to teaches that a functional variant as described herein comprises no more than or up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid substitutions, deletions and/or additions, which are conservative modifications and do not alter the antibody's function and that a functionally active variant as described herein comprises up to 15, preferably up to 10 or 5, amino acid substitutions, deletions and/or additions, which are conservative modifications and do not alter the antibody's function (page 19, lines 16-22). The examples of the specification disclose newly designed oxMIF antibodies with specific VH substitutions (L5Q, W97Y in SEQ ID NO: 6) and VL substitutions (M30L, F49Y, A51G, P80S, W93F in SEQ ID NO: 9) and combinations thereof (pages 42-43, Table 1). The specification teaches that the new antibodies bind soluble oxMIF and have reduced aggregation and hydrophobicity (Examples 1-2, 8). Thus, in view of the instant specification and claims, one alternative for the anti- oxMIF antibody light chain variable domain comprises SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with 1, 2, 3, 4, or 5 further amino acid substitutions , with the proviso that the tyrosine at position 36 is preserved . An additional alternative for the anti- oxMIF heavy chain variable domain comprises SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with 1, 2, 3, 4 or 5 further amino acid substitutions . However, the specification does not teach any variant s/substitutions of the light and heavy chain variable region amino sequences other than the full-length amino acid sequences of SEQ ID NOs: 9 and 6, respectively or SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F; and SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y. The art recognizes that protein function cannot be predicted from structure alone (Bork, 2000, Genome Research 10:398-400; Skolnick et al., 2000, Trends in Biotech. 18(1):34-39, especially p. 36 at Box 2; Doerks et al., 1998, Trends in Genetics 14:248-250; Smith et al., 1997, Nature Biotechnology 15:1222-1223; Brenner, 1999, Trends in Genetics 15:132-133; Bork et al., 1996, Trends in Genetics 12:425-427). See also Tokuriki et al. (Current Opinion in Structural Biology 19: 596-604, 2009), who teach that mutations are generally destabilizing. For instance, Tokuriki et al. teach at page 596, right column, last paragraph, that “as mutations accumulate, protein fitness declines exponentially...or even more than exponentially...So by the time an average protein accumulates, on average, five mutations, its fitness will decline to <20%.” Further, at page 598, left column, last paragraph, Tokuriki et al. note that 50% of mutations are destabilizing, and >15% of mutations are highly destabilizing, and of the about 5% of mutations that are stabilizing values...many of these mutations result in inactive protein. Indeed, Tokuriki et al. conclude that “a more comprehensive understanding of how mutations affect protein fitness within living cells is needed, including their combined effects on function, thermodynamic and kinetic stability, and clearance through aggregation and degradation” (see page 602, left column, 2nd paragraph). Fenton et al. (Medicinal Chemistry Research 29:1133-1146, 2020) also 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 nonconserved 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. Bhattacharya et al. ( PLoS ONE 12(3): e0171355, 2017) 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). Furthermore, when multiple mutations are introduced, there is even less predictability. For evidence thereof, see Guo et al. (PNAS USA 101(25):9205-10, 2004), who state that the effects of mutations on protein function are largely additive (page 9207, left column, full paragraph 2). Fenton et al. supra, also acknowledge this (see abstract). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). Even minor changes in the amino acid sequences of the heavy and light variable regions may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc Natl Acad Sci USA. Vol 79, page 1979, 1982 ; cited on the IDS of 26 February 202 6 ) and Zhang et al. ( mAbs 7(1): 42-52, 2005; page 45, column 2)). Zhang et al. also indicate that minor variations in variable heavy and light chain CDR1s and CDR2s may lead to loss of antigen binding (page 46, column 1). A dditionally, it is not well established in the art that all variable domains are amenable to modifications much less even conservative. Numerous publications acknowledge that conservative substitutions would in fact change the binding ability of antibodies if not substantially reduce the affinity. Brummell et al. (Biochemistry 32:1180-1187 (1993)) found that mutagenesis of the four HCDR3 contact residues for the carbohydrate antibody (Salmonella B O-polysaccharide) in no instance improved affinity but 60% of the mutants resulted in a 10-fold drop in binding constant (affinity electrophoresis value of 0.85), while still other mutants were lower (Table 1 and p. 1183, Col. 2, ¶2 to p . 1184, Col. 1, ¶1). Brummell demonstrate that no substitution retained antigen binding affinity similar to the wild type antibody despite targeted, conservative substitutions in known contact sites. Kobayashi et al. (Protein Engineering 12:879-844 (1999)) disclose that a scFv for binding a DNA oligomer containing a (6-4) photoproduct with Phe or Tyr substitutions at Trp 33 retained “a large fraction of the wild-type binding affinity, while the Ala substitution diminished antigen binding” (Table 1). However, Kobayashi et al. note “replacing Trp 33 with Phe or Ala alters the local environment of the (6-4) photodimer since binding is accompanied by large fluorescence increases that are not seen with the wild-type scFv ” (p. 883, Col. 2, ¶3). Burks et al. (PNAS 94:412-417 (1997)) disclose scanning saturation mutagenesis of the anti-digoxin scFv (26-10) which also binds digitoxin and digoxigenin with high affinity and with 42-fold lower affinity to ouabain. One hundred fourteen mutant scFvs were characterized for their affinities for digoxin, digitonin, digoxignenin and oubain . Histogram analysis of the mutants (Figure 2) reveals that “not all residues are optimized in even high affinity antibodies such as 26-10, and that the absence of close contact with the hapten confers higher plasticity, i.e., the ability to tolerate a wider range of substitutions without compromising binding (p. 415, Col. 2, ¶4- p. 416, ¶1). Vasudevan et al. (Blood Cells Mol Diseases 32: 176-181, 2004) indicate that the single amino acid substitution at position 108 in the H3 loop of monoclonal antibody AP7.4 alters the shape of the loop and changes the binding specificity from integrin αIIbβ3 to integrin αvβ3 (page 177, column 1; Table 1; page 180 through page 181, column 1). Colman (Research in Immunol. 145:33-36 (1994)) teach that single amino acid changes within the interface of an antibody-antigen complex are important and that inasmuch as the interaction can tolerate amino acid sequence substitutions, “a very conservative substitution may abolish binding” while “in another, a non-conservative substitution may have very little effect on the binding” (p. 35, Col. 1, ¶1). Relevant art teaches that while CDR3 is important for antigen-binding, the conformations of other CDRs as well as framework residues also influence binding. Wu et al. (J Mol Biol. 294: 151-162, 1999) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col) but certain residues have been identified as important for maintaining conformation. Sela- Culang et al. (Front Immunol 4: 302, 2013) also teach that it is now well-established that some of the framework residues may play an important role in antigen binding (page 7, column 1, last full paragraph through entirety of column 2). The level of skill required to generate the antibodies is that of a molecular immunologist, and one of ordinary skill in the art would have been required to identify candidate amino acid residues for substitution in the light and heavy chain variable regions, perform the mutagenesis on the light and heavy chain variable regions, produce and express the modified antigen-binding agents, and measure binding characteristics (e.g., binding specificity, equilibrium dissociation constant (K D ), dissociation and association rates (K off and K on respectively), and binding affinity and/or avidity compared with the parent binding agent). The technology to perform these experiments was available at the time of application filing, but the amount of experimentation required to generate even a single light/heavy chain variable region-modified antibody meeting all of the claim limitations would not have been routine, much less could one of ordinary skill in the art predict that any one or combination of all the light/heavy chain variable region amino acid substitutions encompassed by the claims would result in just any antibody or antigen binding fragment thereof having retained the binding activity to oxMIF , as well as having reduced aggregation potential and reduced hydrophobicity . Because of this lack of guidance in the instant specification, the extended experimentation that would be required to determine which amino acid sequences and modifications would be acceptable to retain occluding structural and functional activity, and the fact that the relationship between the sequence of a protein/peptide and its tertiary structure (i.e. its activity) are not well understood and are not predictable, it would require an undue amount of experimentation for one of skill in the art to arrive at the large number of light and heavy chain variable region sequences of the encompassed claims. Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the genus of anti- oxMIF antibodies that comprise a light chain variable domain comprising SEQ ID NO: 9 w ith 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with any 1, 2, 3, 4, or 5 further amino acid substitutions , with the proviso that the tyrosine at position 36 is preserved ; and a heavy chain variable domain comprising SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with any 1, 2, 3, 4 or 5 further amino acid substitutions (and polynucleotides encoding such) in the claims in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher , 166 USPQ 19 24 (CCPA 1970). Due to the large quantity of experimentation necessary to generate and screen oxMIF antibodies that comprise light/heavy chain variable region sequence variants with any 1, 2, 3, 4, or 5 further amino acid substitutions that are still capable of binding oxMIF and have reduced aggregation and hydrophobicity ; the lack of direction/guidance presented in the specification regarding same; lack of working examples; the teachings of the prior art; the complex nature of the invention; the unpredictability of the effects of heavy/light chain alterations on antibody activity; and the breadth of the claims, undue experimentation would be required of the skilled artisan to use the claimed invention. 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 . 8. Claim s 1 , 2, 4 , 5, 13, 15 , 18 - 2 3, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-9, 11, 13-16, and 21-27 of copending Application No. 18/275,179 . Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims recite the same recombinant anti- oxMIF antibody or antigen binding fragment thereof that has reduced aggregation potential and reduced hydrophobicity; nucleic acids encoding such; and a method of treating cancer by administering such antibody . Claim 1 of the instant application recites a recombinant anti- oxMIF antibody or an antigen binding fragment thereof having reduced aggregation potential and reduced hydrophobicity, comprising the following variable domains: (a) a light chain variable domain, wherein the light chain variable domain comprises: (i) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, or ( ii ) SEQ ID NO: 9 with 1, 2, 3, 4, or 5 amino acid substitutions selected from M30L, F49Y, A51G, P80S and W93F, and with 1, 2, 3, 4, or 5 further amino acid substitutions, with the proviso that the tyrosine at position 36 is preserved; and (b) a heavy chain variable domain, wherein the heavy chain variable domain comprises: (i) SEQ ID NO: 6, (ii) SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, or (iii) SEQ ID NO: 6 with 1 or 2 amino acid substitutions selected from L5Q and W97Y, and with 1, 2, 3, 4 or 5 further amino acid substitutions, wherein amino acid positions are numbered according to Kabat, and wherein a