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 1-15-26 election of the species of compound to be used in the claimed method of producing an antibody which is a polyanionic compound species of “an anionic polysaccharide,” wherein the sub-species of “anionic polysaccharide” is “a sulfated polysaccharide,” and wherein the sub-sub-species of “anionic polysaccharide” in the sulfated polysaccharide which is “dextran sulfate” 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)). Claims 1-20 are pending. Claims 1-3, 7-16 and 20 are under examination as they read on a method of producing an antibody comprising culturing in the presence of a polyanionic compound species of “an anionic polysaccharide,” wherein the sub-species of “anionic polysaccharide” is “a sulfated polysaccharide,” and wherein the sub-sub-species of “anionic polysaccharide” in the sulfated polysaccharide which is “dextran sulfate.” Claims 4-6 and 17-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1-15-26. 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. Claims 3 and 16 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. Claims 3 and 16 recite “wherein the sulfated polysaccharide is at least one selected from the group consisting of dextran sulfate and a salt thereof, glycosaminoglycan, and proteoglycan comprising a sulfate group.” The use of Markush - type language to refer to “dextran sulfate and a salt thereof” would be confusing to the ordinarily skilled artisan because , on the one hand it would be unclear if “dextran sulfate” and “a salt thereof’ are to be understood as separate choices where “dextran sulfate” refers to the anionic form of dextran in the absence of a counter-ion, such as Na + or K + , which is separate from the “salt thereof” form where the anionic dextran sulfate is ionically bound to, e.g., a Na+ counter-ion ; or , if on the other hand, in the alternative , the phrase “wherein the sulfated polysaccharide is at least one selected from the group consisting of dextran sulfate and a salt thereof , glycosaminoglycan” should instead be interpreted as referring to a single species which is “dextran sulfate in a salt form” wherein the skilled artisan is meant to equate the phrase “dextran sulfate and a salt thereof” with the phrase “dextran sulfate in a salt form?” 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. Claim(s) 1-3, 7-16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Maeta et al. (20180179298 , cited on an IDS ) in view of Park et al. (Biotechnol. Prog., 2016, Vol. 32, No. 5 , 1113-1122, cited on an IDS ) as evidenced by Heinz et al. (Adv Polym Sci (2006) 205: 199–291 , cited herewith ). Table 1 of Maeta shows the positions where mutations were introduced in light FR3 residues of the Example 1 antibodies anti-insulin antibody and anti-thyroid-stimulating hormone receptor (TSHR) antibody, i.e., at amino acid positions 63, 65, 67, 70, 72 of the light chain FR3 according to Chothia numbering. For example, at para 106 Maeta teaches “In order to introduce a mutation in FR3 defined by the Chothia method in the light chain of each antibody, PCR was carried out using the plasmid containing the wild-type anti-insulin antibody gene obtained in the above (1.1.3), the wild-type anti-TSHR antibody gene obtained in the above (1.2), and the primer represented by the following base sequence….a KS variant is a variant in which 5 amino acid residues of FR3 are mutated to lysine residues, a RS variant is a variant in which 5 amino acid residues of FR3 are mutated to arginine residues, and a R3 variant is a variant in which 3 amino acid residues ofFR3 are mutated to arginine residues.” At para 125 of Example 1, Maeta further teaches : “An antibody in which the 63rd, 65th, 67th, 70th and 72nd serine residues of the light chain FR3 defined by the Chothia method in the wild-type anti-insulin antibody and the wild-type anti-TSHR antibody were substituted with charged amino acid residues (aspartic acid residues, glutamic acid residues, lysine residues or arginine residues) was obtained. An antibody in which the 63rd, 65th and 67 th serine residues of the light chain FR3 defined by the Chothia method in the wild-type anti-insulin antibody were substituted with charged amino acid residues ( arginine residues) was obtained.” In Example 2 Maeta characterizes the affinity of the antibodies of Example 1 for their cognate antigens. At para 136 Maeta concludes: “From Table 3 and FIG. lA, the K D values of the R3 variant, the R 5 variant and the K 5 variant of the anti-insulin antibody were lower than the K D value of the wild type . The K D values of the D5 variant and the ES variant were higher than the K D value of the wild type. Therefore, as to the anti-insulin antibody, it was found that an antibody with affinity for an antigen improved as compared to the wild type can be prepared by mutating 3 or 5 amino acid residues of FR3 to basic amino acid residues …. , ” and a para 137, “…[o]n the other hand, the K D value of the R 5 variant of the anti-TSHR antibody was comparable to the K D value of the wild type. That is, as to the anti-TSHR antibody, it is suggested that affinity does not change even when 5 amino acid residues of FR3 are mutated to basic amino acid residues.” Similar results are set forth in Example 5 at para 180 where, again like above in Example 2 , “…as to the anti-lysozyme antibody, it was found that an antibody with affinity for an antigen improved as compared to the wild type can be prepared by mutating 5 neutral amino acid residues of FR3 to basic amino acid residues . It was found that an antibody with affinity for an antigen reduced as compared to the wild type can be prepared by mutating 5 neutral amino acid residues of FR3 to acidic amino acid residues. These results were similar to those of the variant of the anti-insulin antibody in Example 2 . Therefore, it is suggested that, in the antibody whose electrical characteristic of CDR is neutral, it is possible to control the orientation of the antigen-binding site by electrostatic interaction caused by the introduction of a charged amino acid residue in FR3.” At para 55, Maeta further teaches “…in the production method of the present embodiment, the antibody obtained in the above substitution step is recovered. For example, a host cell expressing an antibody whose affinity for an antigen has been altered is dissolved in a solution containing an appropriate solubilizer to liberate the antibody in the solution. When the above host cell secretes an antibody whose affinity for an antigen has been altered into the medium, the culture supernatant is recovered. The liberated antibody can be recovered by methods known in the art such as affinity chromatography …. ” With respect to the particular type of host cell, at para 77 Maeta teaches “…The scope of the present disclosure also includes a host cell containing the vector. The type of the host cell is not particularly limited. The host cell can be appropriately selected from eukaryotic cells, prokaryotic cells, mammalian cells and the like.” At para 62 Maeta further teaches “The modified antibody may be an antibody recognizing any antigen. The antibody class may be IgG, IgA, IgM, IgD or IgE, and is preferably IgG.” To summarize, Maeta teaches a method for producing an antibody, e.g., an IgG antibody, comprising culturing an animal cell into which a gene encoding an antibody has been introduced whereby the animal cell produces the antibody, and then retrieving said antibody from the culture supernatant, wherein the antibody is an antibody in which at least 3 amino acid residues of framework region 3 (FR3), e.g., residues 63, 65 and 67, or wherein the antibody is an antibody in which at least 5 amino acid residues of framework region 3 (FR3), e.g., residues 63, 65, 67, 70 and 72, are substituted each independently with an arginine residue or a lysine residue, and wherein said substituted antibody has improved affinity for its cognate antigen as compared to the antibody before substitution of the FR3 amino acid residues. However, Maeta does not explicitly teach “a method for producing an antibody, comprising culturing in a presence of a polyanionic compound an animal cell into which a gene encoding an antibody has been introduced whereby the animal cell produces the antibody / a method for producing an antibody, comprising the steps of: culturing in vitro in a presence of a polyanionic compound an animal cell into which a gene encoding an antibody has been introduced to allow the animal cell to produce the antibody; and retrieving the antibody produced by the animal cell in the culturing step, wherein the polyanionic compound is at least one selected from the group consisting of an anionic polysaccharide and an anionic polyamino acid, and the antibody is an antibody in which at least 3 amino acid residues of framework region 3 (FR3) are substituted each independently with an arginine residue or a lysine residue” or dependent claims thereof. At page 1113, 1 st full paragraph of the Introduction Park teaches: “Chinese hamster ovary (CHO) cells are the predominant host used to produce therapeutic proteins including monoclonal antibodies (mAbs). 1 For large-scale commercial production of antibodies, CHO cells are adapted to grow to high densities (10 6 - 1 0 7 cells/mL) in single cell suspension cultures, which are readily scalable to over 10,000 L stirred tank bioreactors. 2–4 Despite considerable research on adaptation processes, CHO cells frequently form aggregates, especially in high density cultures, including fed-batch cultures. 5,6 …. Large aggregates in recombinant CHO (rCHO) cell cultures can be detrimental to therapeutic protein production by creating heterogeneous cell population and product quality, which is characterized by nutrient limitations and ultimately loss of cell viability and productivity. 9 ” Park tested the effects of adding various concentration of various molecular weight forms of dextran sulfate (DS) to the cultures of two recombinant CHO cell lines (rCHO) that produce mAbs, “SM-0.025” and “CS13-1.00” (see page 111, 1 st para). As shown in Tables 1 and 2, the maximum mAb concentration (MMC) that resulted from culturing each of the “SM-0.025” and “CS13-1.00” cell lines in the presence of the various concentration of various molecular weight forms of dextran sulfate were generally higher than control cultures lacking DS. In general, the level of DS ranged from 0.1 g/L to 1.0 g/L. At page 1120, last full paragraph – page 1121, 1 st full paragraph Park concludes: “DS addition did not negatively affect the three quality attributes , including aggregation, charge variation, and N-glycosylation of mAbs for both cell lines…. For both cell lines, DS addition affected the charge variation of mAbs. Depending on the MW and concentration, DS addition decreased the basic charge variants in mAbs .” “…it was reported that higher copper concentration in culture media resulted in higher levels of basic charge variants. 43 Thus, decreased copper concentration, resulting from the binding of copper ions to highly sulfated DS, may also responsible in part for decreased levels of basic charge variants in SM-0.025 and CS13-1.00 cell cultures. Overall, the addition of DS produced a positive effect on mAb quality .” “ In conclusion, the addition of DS in rCHO cell cultures, regardless of the MW and concentration of DS used, improved cell growth and viability…. to maximize the beneficial effect of DS addition on mAb production, the MW and concentration of DS should be optimized for each specific rCHO cell line . ” Given the reference teachings it would have been obvious to the ordinarily skilled artisan that the method for producing an antibody, e.g., an IgG antibody, comprising culturing an animal cell into which a gene encoding an antibody has been introduced whereby the animal cell produces the antibody, and then retrieving said antibody from the culture supernatant, wherein the antibody is an antibody in which at least 3 amino acid residues of framework region 3 (FR3), e.g., residues 63, 65 and 67, or wherein the antibody is an antibody in which at least 5 amino acid residues of framework region 3 (FR3), e.g., residues 63, 65, 67, 70 and 72, are substituted each independently with an arginine residue or a lysine residue, and wherein said substituted antibody has improved affinity for its cognate antigen as compared to the antibody before substitution of the FR3 amino acid residues described by Maeta could be improved by expressing said antibodies from CHO cells, since expression and purification of mAbs from this cell type is widely used for large-scale commercial production of antibodies , and further by growing said mAb expressing CHO cells in the presence of dextran sulfate which is present at various molecular weights (MW, e.g., at 4,000 Da, 15,000 Da or 40,000 Da), at various concentrations from 0.1 g/L to 1.0 g/L, with the expectation that determination of the optimal DS MW and optimal DS concentration is an art-recognized results effective variable as illustrated by the teachings of Park. A reason one of ordinary skill in the art would have been motivated to produce the antibodies of Maeta in CHO cells grown in the presence of DS was because, as described by Park, the presence of DS optimized for MW and concentration increases mAb production and quality, e.g., by diminishing the amount of basic charge variants due to “oxidation of unstable amino acid residues (methionine, cysteine, lysine, histidine, and tryptophan) or C-terminal lysine/glycine amidation. 39,40 ” Note that as evidenced by Heinze at page 219, 1 st paragraph , “dextran sulfate” is synonymous with “dextran sulfuric acid half ester and its sodium salt” meaning that dextran sulfate is necessary present as a sodium salt when in its powder form prior to addition to the cell culture at which point it becomes an aqueous solution form of dextran sulfate . In view of the reference teachings it was apparent that one of ordinary skill in the art would have had a reasonable expectation of success in arriving at the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT ZACHARY S SKELDING whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-9033 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9-5 EST . 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ZACHARY S SKELDING/ Primary Examiner, Art Unit 1644