CTNF 18/820,925 CTNF 98127 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-fti AIA The present application is being examined under the pre-AIA first to invent provisions. Priority The instant application is a continuation of U.S. Application No. 17/217,706, filed March 30, 2021, which is a continuation of U.S. Application No. 16/412,791, filed May 15, 2019, now U.S. Patent No. 10,982,003, issued April 20, 2021; which is a continuation of U.S. Application No. 16/138,704, filed September 21, 2018, now abandoned; which is a continuation of U.S. Application No. 15/881,308, filed January 26, 2018, now abandoned; which is a continuation of U.S. Application No. 15/623,226, filed June 14, 2017, now abandoned; which is a continuation of U.S. Application No. 14/670,079, filed March 26, 2015, now U.S. Patent No. 9,714,293, issued July 25, 2017; which is a continuation of U.S. Application No. 13/945,531, filed July 18, 2013, now abandoned; which is a continuation of U.S. Application No. 12/852,377, filed August 6, 2010, now U.S. Patent No. 8,512,983, issued August 20, 2013; which claims priority under 35 USC § 119(e) and the benefit of U.S. Provisional Application No. 61/232,889, filed August 11, 2009. Benefit of priority claims to 8/11/2009 is acknowledged. Information Disclosure Statement 06-52 The information disclosure statement (IDS) submitted on 1/17/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Due to the large number of references cited (approximately 340), the references have been afforded a cursory review (e.g. title, Abstract, and keyword search), in accordance with the time provided for considering IDS submissions. If there are any particular references that the Applicant deems relevant to patentability, the Applicant is respectfully asked to point out and/or provide a brief description of such references. Copies of all of the cited Foreign Parents and NPL references appear to have been provided in the parent applications. Applicant’s assistance is requested in confirming that all of the referenced Foreign Applications and NPL documents are available from the prosecution history of the parent applications. Response to Amendment Applicant’s amendment to the claim filed 8/30/2024 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims. Claims 1-40 are cancelled. Claims 41-64 are pending and have been examined on the merits. 07-30-03-h AIA Claim Interpretation The following terms have been interpreted according to the B.R.I. as known to the art and in consideration of any special definitions in the specification: the specification [0067] defines a “batch culture”, recited in claim 52, as one in which all components for cell culturing (including the animal cells and all culture nutrients) are supplied to the culturing vessel at the start of the culturing process”; “dhfr − CHO cell”, recited in claim 53, refers to a dihydrofolate reductase (DHFR) deficient CHO cell ([0062] of the specification); “bevacizumab” is a recombinant humanized monoclonal IgG1 antibody against VEGF; “rituximab” is a genetically engineered chimeric murine/human monoclonal IgG antibody directed against the CD20 antigen; and “trastuzumab” is a humanized IgG monoclonal antibody that selectively binds with high affinity to the extracellular domain of the human epidermal growth factor receptor 2 protein, HER2). Claim Rejections - 35 USC § 112(b) 07-30-02 AIA 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. 07-34-01 Claim 41-64 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 41, 63, and 64 refer to a cell culture medium that is “essentially” free of glutamine. Clarification of the amount of glutamine that is encompassed by the claim language is requested. It is unclear what concentration would be essentially free of glutamine in the medium. Is the medium glutamine-free? Suggest stating glutamine-free medium. Claim 63 recites a “method of improving viability of a Chinese hamster ovary (CHO) host cell in a cell culture, the method comprising culturing the CHO host cell in a production phase cell culture medium...”. The claimed method, as presented, is indefinite because one would not be appraised of the metes and bounds of the claimed improvement. There are no means recited in the claim for one to determine if the viability of Chinese hamster ovary (CHO) host cells in the culture media has been improved. Further, there is no recitation of a base method or a control method for which the improved viability is to be compared to. The improved viability is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the phrase “improving viability” recited in the preamble of the claim is a relative term which renders the claim indefinite. For the purposes of comparing the claims to any relevant prior art, the claim element has been interpreted as a desired result recited in the preamble, and the main action step of the method is the culturing of the CHO cells in the defined production phase cell culture medium. Claim Rejections - 35 USC § 102 07-07-fti The following is a quotation of the appropriate paragraphs of pre-AIA 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 – 07-08-fti 07-08 (a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent. 07-09-fti 07-09 (b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States. 07-15-fti Claim s 41-42, 49-53, and 63-64 are rejected under pre-AIA 35 U.S.C. 102 (a)/(b) as being anticipated by Dyring et al. (1994; Observations on the influence of glutamine, asparagine, and peptone on growth and t-PA production of Chinese hamster ovary (DHO) cells. Cytotechnology 16: pp 37-42; on IDS submitted 1/17/2025- a complimentary copy is provided with this action) . Dyring et al. discloses the culturing of dhfr - CHO cells producing the recombinant protein t-PA in glutamine free (“Glutamine-free DMEM (Gibco)”), that is “supplemented with asparagine and/or glutamine to a total concentration of 10.2 mM or 5.1 mM. The ratio between glutamine and asparagine was: 1:0, 1:3, 1:1, 3:1 and 0:1.” (page 38, left col, under “ Media ”). Table 1, on page 39, in Dyring discloses particular embodiments of the culture compositions and media ingredients used, which includes inter alia : 0 gln with 5.1mM asn (row 9); 5.1mM gln with 0 asn (row 5); 0 gln with 10.2mM asn (row 14); 10.2mM gln with 0 asn (row 10). Figure 2 of Dyring discloses embodiments with 5mM asparagine or 5mM glutamine (see Materials and methods, pg 38, left-hand column), and it was found that the use of asparagine without glutamine resulted in a maximal output of t-PA with serum containing media. The cells were also tested for cell viability and growth (Figure 3) and for t-PA concentration over time (Figure 5) in various serum-free growth medias (i.e. those recited in Table 1). In the results demonstrated by Dyring et al., higher titers of t-PA were obtained when the media was supplemented with asparagine in place of glutamine (Figure 2, with serum-containing media). Dyring et al. postulates that “the results show, that it may be beneficial to substitute at least part of the glutamine with asparagine, if not for any other reason, it gives a more stable cultivation medium” (pg 41, Discussion, right hand column, last paragraph). Dyring thus discloses a production phase cell culture composition comprising Chinese hamster ovary (CHO) cells and a production phase cell culture medium (media used to produce t-PA recombinant protein), wherein the production phase cell culture medium comprises asparagine at a concentration in the range of 2.5 mM to 15 mM (5.1 mM or 10.2 mM), wherein the production phase cell culture medium is essentially free of glutamine, and therefore anticipates claim 41. Regarding claim 42, the asparagine concentrations disclosed in Dyring et al. include 10.2mM, which anticipates the claimed range of 10mM to 15mM asparagine. Regarding claim 49, Dyring discloses serum-free media that fulfill all of the limitations. Regarding claims 50 and 51, Dyring discloses that the media additional comprises: 3.5 g/L glucose, 3.7 g/L NaHCO 3 , 0.122 g/L Na-pyruvate, 17.25 mg/L L-proline, 5 mg/L transferrin, 1.22 mg/L Ethanolamine, 0.656 µg/L selenium, 2 g/L dextran, 2.383 g/L HEPES, 2 g/L PEG 20.000 , 0.566 ml 0.125 M mercaptoethanol, 8 g/L casein peptone, 5.7 mg/L stearic acid, 0.3 mg/L insulin, and 4 mg/L ZnCl 2 (page 38, left col, under “ Media ”). Dyring thus discloses that the composition further comprises at least one or more ingredients selected from the group consisting of: i) an energy source (e.g. pyruvate); ii) essential amino acids (e.g. L-Proline); iii) vitamins; iv) free fatty acids (e.g. stearic acid); and v) trace elements (e.g. selenium, zinc), as in claim 50; and at least one or more selected from the group consisting of: i) hormones and other growth factors; ii) salts and buffers (e.g. HEPES, NaHCO 3 ), as in claim 51. Regarding claim 52, Dyring discloses that “One of the advantages of using asparagine instead of glutamine is that large amounts of asparagine can be added from the beginning of the cultivation without the contribution from decomposition getting particularly high. When using glutamine, it is necessary to add small amounts at short intervals (fed-batch) in order to obtain an equivalent low ammonium concentration”. Thus, Dyring discloses a batch culture phase cell culture medium using asparagine, wherein in a large amount of asparagine is added at the initiate of the culture (i.e. a batch culture). Claim 53 recites that the CHO host cells are dhfr - CHO cells, which are used in Dyring. Dyring anticipates the method recited in claim 63 that comprises a step of culturing the CHO host cell in a production phase cell culture medium comprising asparagine at a concentration in the range of 2.5 mM to 15 mM (wherein Dyring teaches 5.1 mM and 10.2 mM), wherein the production phase cell culture medium is essentially free of glutamine. Here, the recitation of “improving cell viability” has been interpreted as a desired result in the preamble language, and the comparison to what cell viability is compared is not stated, as described in the 112(b) rejection above. Thus, the preamble language is not being considered as limiting the claim. The only required method step is the culturing of the CHO host cells in this particular media composition, as performed in Dyring. Regarding claim 64, Dyring also discloses a cell culture medium for the production of a polypeptide in a production phase by a Chinese hamster ovary (CHO) host cell, the cell culture medium comprising asparagine at a concentration in the range of 2.5 mM to 15 mM (e.g. 5.1 mM and 10.2 mM), wherein the cell culture medium is essentially free of glutamine. There is nothing in the reference to indicate that the media is not “ready to use”. In fact, Dyring successfully cultures CHO cells in these media for recombinant protein production. For the reasons discussed above, Dyring is deemed to anticipate claims 41-42, 49-53, and 63-64, which are herein rejected under pre-AIA 35 U.S.C. 102 . Claim Rejections - 35 USC § 103 07-20-fti The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-fti The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-20-02-fti This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a). 07-21-fti Claim 43 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Dyring et al. (1994; Cytotechnology 16: pp 37-42, of record) . Dyring et al. discloses the culturing of dhfr - CHO cells producing the recombinant protein t-PA in glutamine free (“Glutamine-free DMEM (Gibco)”), that is “supplemented with asparagine and/or glutamine to a total concentration of 10.2 mM or 5.1 mM. The ratio between glutamine and asparagine was: 1:0, 1:3, 1:1, 3:1 and 0:1.” (page 38, left col, under “ Media ”). Table 1, on page 39, in Dyring discloses particular embodiments of the culture compositions and media ingredients used, which includes inter alia : 0 gln with 5.1mM asn (row 9); and 0 gln with 10.2mM asn (row 14), as discussed above. Dyring thus teaches a production phase cell culture composition comprising Chinese hamster ovary (CHO) cells and a production phase cell culture medium (media used to produce t-PA recombinant protein), wherein the production phase cell culture medium comprises asparagine at a concentration in the range of 2.5 mM to 15 mM (specifically at 5.1 mM or 10.2 mM), wherein the production phase cell culture medium is essentially free of glutamine. Regarding claim 43, the asparagine concentrations disclosed in Dyring et al. include concentrations at specifically 5.1mM and 10.2mM (see e.g. Table 1). Thus, Dyring does not explicitly teach that the claimed composition having an asparagine concentration of 10mM. Regardless, to one of ordinary skill in the art, prior to the time of the invention, it would have been obvious over the teachings of Dyring to produce the claimed cell culture composition comprising a Chinese hamster ovary (CHO) host cell and a glutamine-free production phase cell culture medium comprising asparagine at a concentration of 10 mM. The determination of an optimum concentration of the result-effective variable asparagine would have been a matter of routine optimization within the conditions taught in Dyring. MPEP § 2144.05 discusses “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”, and “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”. MPEP § 2144.05 also describes that the determination of suitable or effective concentration of a known composition (or performing a known method) can be determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal results, as these are variable parameters attainable within the art. “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller , 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, in the instant case, arriving at the claimed concentration of 10mM asparagine, when a concentration of 10.2mM is taught as suitable in Dyring, would have been prima facie obvious with a reasonable expectation of success as Dyring teaches using glutamine-free media having concentrations of both 5.1mM and 10.2mM successfully for production of the recombinant protein from CHO cells, the same cells and conditions as in the instant claim. Accordingly, the invention of claim 43 as a whole would have been prima facie obvious, especially in the absence of sufficient, clear, and convincing evidence to the contrary . 07-21-fti Claim s 54-62 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Dyring et al. (1994; Cytotechnology 16: pp 37-42, of record), as applied to claim 41 above, further in view of Kallmeier, (US PGPub 20060003405, cited on IDS filed 1/17/2025) and Lazar, (US PGPub 20050054832, cited on IDS filed 1/17/2025) . The teachings of Dyring include all of those discussed above. Dyring teaches a production phase cell culture composition comprising Chinese hamster ovary (CHO) cells and a production phase cell culture medium used to produce therapeutic tPA recombinant protein, wherein the production phase cell culture medium comprises asparagine at a concentration in the range of 2.5 mM to 15 mM (at 5.1 mM or 10.2 mM), wherein the production phase cell culture medium is essentially free of glutamine, as recited in claim 41. However, Dyring does not teach nor reasonably suggest a composition wherein the CHO host cell comprises one or more nucleic acids encoding a therapeutic IgG antibody, nor does the reference disclose that the IgG antibody is one of the alternatives in claims 56-62. Kallmeier teaches methods of expressing a recombinant protein comprising steps of culturing a CHO cell transfected with an expression vector and harvesting the product protein (Abstract, [0012]-[0014]). Kallmeier teaches a recombinant product includes any protein of interest, e.g. therapeutic proteins such as interleukins or enzymes or subunits of multimeric proteins such as antibodies or fragments thereof and that “more preferably, the first or product protein is an antibody or engineered antibody or a fragment thereof, most preferably it is an Immunoglobulin G (IgG) antibody ” ([0015]). Kallmeier also teaches that (for some embodiments) glutamine in the medium or feed is mostly substituted by its equivalents and/or precursors, that is asparagine and/or glutamate” ([0029]). Kallmeier thus establishes that CHO cells can be used in glutamine-free media to produce IgG antibodies. Lazer, drawn to the production of optimized antibody fragments, Fc fragments, Fc fusions, and method for their generation (Abstract), teaches CHO cell culture methods (Example 12, [0299]) and teaches that the produced antibodies may be nonhuman, chimeric, humanized, or fully human (see para [0080]). Lazer additionally teaches that antibodies known to the art at the time of the invention include, among others, ([0107], and claim 32) the following: trastuzumab, an anti-HER2/neu antibody ([0012], [0107]); rituximab, an anti-CD20 antibody ([0006], [0107]); and bevacizumab, an anti-VEGF antibody ([0107]). Therefore, to one of ordinary skill in the art at or before the time the invention was made, it would have been prima facie obvious to modify the protein production composition having a glutamine-free media comprising asparagine as taught in Dyring according to the teachings of Kallmeier and Lazer, by substituting CHO cells that produce a therapeutic IgG antibody for the recombinant CHO cells that express tPA used in Dyring, for the express purpose of generating medically useful IgG antibodies, as taught in Kallmeier, and it would have been obvious to produce a chimeric, humanized, or human IgG antibody according to the teachings of Lazer, including any therapeutically useful IgG antibodies known to the art. Lazer and Kallmeier are analogous to the instant invention as each are directed to production of antibodies using CHO cell culture. One would have been motivated by the teachings of Lazer and Kallmeier to produce any of these monoclonal antibodies known to the art using an improved CHO cell culture method, such as the methods using the glutamine-free culture media that is taught in Dyring. Further, Dyring teaches that serum-free and glutamine-free media with substituted asparagine has benefits such as the ability to add a large bolus of asparagine, and this avoids the problems of ammonia produced by glutamine in typical culture. MPEP § 2143, KSR rationale B) states that an invention is obvious when the substitution of one known element for another yields predictable results to one of ordinary skill in the art. In the instant case, the production of recombinant proteins in CHO cells in a composition equivalent to that of the instant claims is taught in Dyring, and the production of IgG antibodies in CHO cells is clearly well-established in the art, as demonstrated in Kallmeier and Lazer, thus it would have been a matter of substituting the recombinant protein sequence (changing the transfected polynucleotide vector) for any of the therapeutic antibodies known in the art, such as the specific ones named in claims 57-62, as taught in Lazer. Further, at least the production of one or more of the therapeutic antibodies- particularly anti-HER2 antibodies; anti-CD20 antibodies; or anti-VEGF antibodies- named in claim 56 would have been obvious over the combination of Dyring, Kallmeier, and Lazer. From the teachings of the cited references, it is apparent that there would have been a reasonable expectation of success in combining the teachings of Dyring, Kallmeier, and Lazer to arrive at the claimed invention because molecular cloning, CHO cell transfection, and CHO cell antibody production are well known techniques in the art, as evidenced by Kallmeier and Lazer. Further, the use of glutamine-free media supplemented with asparagine for CHO cells is established by the teachings of Drying and further discussed in embodiments of Kallmeier. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, as evidenced by the cited references, especially in the absence of evidence to the contrary. Nonstatutory Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 41-43 and 49-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 8,512,983 . Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent claims recite production methods requiring recombinant CHO cells in glutamine-free production culture media, with asparagine at or around the same concentrations recited in the instant claims. The instant independent claims recite a production phase cell culture composition comprising CHO host cells and a production phase cell culture medium, wherein the production phase cell culture medium comprises asparagine at a concentration in the range of 2.5 mM to 15 mM, wherein the production phase cell culture medium is essentially free of glutamine (as in claim 41), a ready-to-use cell culture medium (as in claim 64), and a method of improving viability of a CHO host cells in the product cell culture media (claim 63). The 8,512,983 patent recites a process for producing a polypeptide in a mammalian host cell expressing said polypeptide, comprising culturing the mammalian host cell in a production phase of the culture in a glutamine-free production culture medium containing asparagine, wherein the asparagine is added at a concentration in the range of 7.5 mM to 15 mM, in claim 1. Claim 2 of the reference patent recites that the asparagine is added at a concentration in the range of 7.5 mM to 10 mM, reference claim 4 recites that the host cell is a Chinese Hamster Ovary (CHO) cell, and reference claim 5 recites that host cell is a dhfr - CHO cell. Claim 25 of the ’983 patent recites a ready-to-use glutamine-free cell culture medium containing asparagine for the production of a polypeptide in a production phase, wherein the asparagine is at a concentration in the range of 7.5 mM to 15 mM. Thus, the instant claims 41-43, 53, 63, and 64 are deemed anticipated by the subject matter of the ’983 patent claims. Regarding the instant claims 49-52, claims 6-9 of the reference application recite that: the production medium is serum-free; the production culture medium comprises one or more ingredients selected from the group consisting of 1) an energy source; 2) essential amino acids; 3) vitamins; 4) free fatty acids; and 5) trace elements; the production culture medium additionally comprises one or more ingredients selected from the group consisting of: 1) hormones and other growth factors; 2) salts and buffers; and 3) nucleosides; and the production phase is a batch or fed batch culture phase. Regarding claims 54-56, claims 14 and 17 of the reference application recites that the produced polypeptide is an antibody or antibody fragment which comprises a therapeutic antibody or a biologically functional fragment thereof, while claim 16 recites that the antibody or antibody fragment is chimeric, humanized or human. Reference claim 18 recites a number of therapeutic antibodies, including but not limited to anti-HER2 antibodies anti-CD20 antibodies; anti-IL-8 antibodies; and anti-VEGF antibodies. One of ordinary skill in the art would recognize or determine from the art and the detailed description in the reference applications specification that many of these “therapeutic antibodies” encompass therapeutic IgG antibodies. Thus, claim 54 would have been obvious over the claimed subject matter of the reference claims, particularly over the antibodies disclosed in the reference claim 18. The production of therapeutic IgG antibodies would have been a matter of judicious selection among medically useful polypeptide products known in the art. Likewise, claims 55 and 56 would have been prima facie obvious, if not anticipated, by the subject matter of claims 16-18 in the ’983 application. Regarding claims 57-62, the production of any of these specific antibodies would have been prima facie obvious in view of the recited subject matter in claims 18 and 19 of the reference application (claim 19 recites that “said therapeutic antibody is an antibody binding to a HER receptor, VEGF... CD20”). The specific antibodies of trastuzumab, rituximab, and bevacizumab would have been prima facie obvious to select to one having ordinary skill as these were well-recognized efficacious antibodies for HER2, CD20, and VEGF. The selection of these specific embodiments would have been a matter of judicious selection and routine optimization to one having ordinary skill, in view of all of the claimed subject matter of the reference claim. For at least these reasons, claims 41-43 and 49-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over the subject matter of US 8,512,983. Claims 41-45 and 49-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-76 of U.S. Patent No. 9,714,293. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent claims recite production methods requiring recombinant CHO cells in glutamine-free production culture media, with asparagine at or around the same concentrations recited in the instant claims. The 9,714,293 patent recites a process for producing a polypeptide in a host cell expressing said polypeptide, comprising culturing the host cell in a production phase of the culture in a glutamine-free production culture medium containing asparagine and aspartic acid, wherein the asparagine is added at a concentration in the range of 7.5 mM to 15 mM and wherein the aspartic acid is added at a concentration in the range of 1 mM to 10 mM in claim 1. Claim 3 recites further comprising determining one or more of cell viability, culture longevity, specific productivity and final recombinant protein titer following isolation. Claim 5 of the reference patent recites that the asparagine is added at a concentration in the range of 7.5 mM to 10 mM, reference claim 6 recites that the asparagine is 10mM, reference claim 41 recites that the host cell is a Chinese Hamster Ovary (CHO) cell, and reference claim 42 recites that host cell is a dhfr - CHO cell. Thus, the instant claims 41-45, 53, 63, and 64 are deemed anticipated by the subject matter of the ’293 patent claims. Regarding the instant claims 49-52, claims 7-10 of the reference application recite that: the production medium is serum-free; the production culture medium comprises one or more ingredients selected from the group consisting of 1) an energy source; 2) essential amino acids; 3) vitamins; 4) free fatty acids; and 5) trace elements; the production culture medium additionally comprises one or more ingredients selected from the group consisting of: 1) hormones and other growth factors; 2) salts and buffers; and 3) nucleosides; and the production phase is a batch or fed batch culture phase. Regarding claims 54-56, claims 66-69 of the reference application recites that the produced polypeptide is an antibody or antibody fragment which comprises a therapeutic antibody or a biologically functional fragment thereof (e.g. claim 69), while claim 68 recites that the antibody or antibody fragment is chimeric, humanized or human. Reference claims 70 and 71 recite a number of therapeutic antibodies, including but not limited to anti-HER2 antibodies anti-CD20 antibodies; anti-IL-8 antibodies; and anti-VEGF antibodies. One of ordinary skill in the art would recognize or determine from the art and the specification of the reference application specification that many of these therapeutic antibodies are IgG antibodies. Thus, instant claim 54 would have been obvious over the claimed subject matter of the reference claims, particularly over the antibodies disclosed in the reference claims 70 and 71. The production of therapeutic IgG antibodies would have been a matter of judicious selection among medically useful polypeptide products known in the art. Likewise, instant claims 55 and 56 would have been prima facie obvious, if not anticipated, by the subject matter of claims 66-71 in the reference application. Regarding claims 57-62, the production of any of these specific antibodies would have been prima facie obvious in view of the recited subject matter in claims 71 and 72 of the reference application. Claim 72 recites that the therapeutic antibody is selected from the group consisting of bevacizumab, rituximab, and trastuzumab. For at least these reasons, claims 41-45 and 49-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over the subject matter of US 9,714,293. Claims 41-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 10,982,003 . Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent claims recite production methods requiring recombinant CHO cells in glutamine-free production culture media, with asparagine at or around the same concentrations recited in the instant claims. The 10,982,003 patent recites a process for producing an antibody in a Chinese hamster ovary (CHO) host cell expressing said antibody, comprising culturing the CHO host cell in a production phase of the culture in a glutamine-free production culture medium containing asparagine (reference claim 1), wherein the asparagine is added at a concentration in the range of 2.5 mM to 15 mM (reference claim 2). Claim 16 recites further comprising determining one or more of cell viability, culture longevity, specific productivity and final antibody titer following isolation. Claim 3 of the reference patent recites that the asparagine is added at a concentration in the range of 7.5 mM to 10 mM, reference claim 4 recites that the asparagine is 10mM, and reference claim 14 recites that host cell is a dhfr - CHO cell. Thus, the instant claims 41-43, 53, 63, and 64 are deemed anticipated by the subject matter of the ’003 patent claims. Regarding claims 44 and 45, claims 5 and 6 of the reference application recite identical concentrations of aspartic acid. Regarding claims 46 and 47, claims 7 and 8 of the reference application recite identical concentrations of glutamate. Regarding the instant claim 48, reference claim 9 recites that a) the asparagine is added at a concentration of 10 mM, b) the aspartic acid is added at a concentration of 10 mM, and c) the glutamate is added at a concentration of 1 mM. Regarding the instant claims 49-52, claims 10-13 of the reference application recite that: the production medium is serum-free; the production culture medium comprises one or more ingredients selected from the group consisting of 1) an energy source; 2) essential amino acids; 3) vitamins; 4) free fatty acids; and 5) trace elements; the production culture medium additionally comprises one or more ingredients selected from the group consisting of: 1) hormones and other growth factors; 2) salts and buffers; and 3) nucleosides; and the production phase is a batch or fed batch culture phase. Regarding claims 54-56, claims 18-21 of the reference application recites that the produced polypeptide is an antibody or antibody fragment which comprises a therapeutic antibody or a biologically functional fragment thereof (e.g. claim 20), while claim 19 recites that the antibody or antibody fragment is chimeric, humanized or human. Reference claims 21 and 22 recite a number of therapeutic antibodies, including but not limited to anti-HER2 antibodies anti-CD20 antibodies; anti-IL-8 antibodies; and anti-VEGF antibodies. One of ordinary skill in the art would recognize or determine from the art and the specification of the reference application specification that many of these therapeutic antibodies are IgG antibodies. Thus, instant claim 54 would have been obvious over the claimed subject matter of the reference claims, particularly over the antibodies disclosed in the reference claims 21 and 22. The production of therapeutic IgG antibodies would have thus been a matter of judicious selection among medically useful polypeptide products known in the art. Likewise, instant claims 55 and 56 would have been prima facie obvious, if not anticipated, by the subject matter of claims 18-22 in the reference application. Regarding claims 57-62, the production of any of these specific antibodies would have been prima facie obvious in view of the recited subject matter in claims 23-24, and 29-32 of the reference application. For at least these reasons, claims 41-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over the subject matter of US 10,982,003. Claims 41-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,103,975 ; Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent claims recite production methods requiring recombinant CHO cells in glutamine-free production culture media, with asparagine at or around the same concentrations recited in the instant claims. The reference patent U.S. 12,103,975 claims are drawn to “process for producing a therapeutic IgG antibody in a Chinese hamster ovary (CHO) host cell expressing said antibody, wherein the process comprises culturing the CHO host cell in a production phase of the culture, wherein the culture is essentially free of glutamine, and wherein the culture comprises asparagine provided at a concentration of 10 mM” (as in claim 1 therein). Claim 13 of the ’975 patent recites further comprising determining one or more of cell viability, culture longevity, specific productivity and final antibody titer following isolation. Claim 7 of the ’975 patent recites that host cell is a dhfr - CHO cell. Thus, the instant claims 41-43, 53, 63, and 64 are deemed anticipated by the subject matter of the ’975 patent claims. Regarding claims 44 and 45, claims 2 and 3 of the reference application recite identical concentrations of aspartic acid. Regarding claims 46 and 47, claims 4 and 5 of the reference application recite identical concentrations of glutamate. Regarding the instant claim 48, reference claim 6 recites that the asparagine is at a concentration of 10 mM from claim 1), the aspartic acid is at a concentration of 10 mM, and the glutamate is at a concentration of 1 mM. Regarding the instant claims 49-52, claims 8-11 of the reference application recite that: the production medium is serum-free; the production culture medium comprises one or more ingredients selected from the group consisting of 1) an energy source; 2) essential amino acids; 3) vitamins; 4) free fatty acids; and 5) trace elements; the production culture medium additionally comprises one or more ingredients selected from the group consisting of: 1) hormones and other growth factors; 2) salts and buffers; and 3) nucleosides; and the production phase is a batch or fed batch culture phase. Regarding claims 54, claim 1 of the reference patent recites that the produce polypeptide is a therapeutic IgG antibody. Regarding claim 55, claim 15 recites that the antibody or antibody fragment is chimeric, humanized or human. Regarding claims 56-62, reference claim 16 recites a number of therapeutic antibodies, including but not limited to anti-HER2 antibodies anti-CD20 antibodies; anti-IL-8 antibodies; and anti-VEGF antibodies. Regarding claims 57-62, the production of any of these specific antibodies would have been prima facie obvious in view of the recited subject matter in claims 17-22 of the reference application. For at least these reasons, claims 41-64 are rejected on the grounds of nonstatutory double patenting as being unpatentable over the subject matter of US 12,103,975. Claims 41-58 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,351,641 . Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent claims recite production methods requiring recombinant CHO cells in glutamine-free production culture media, with asparagine at or around the same concentrations recited in the instant claims. The reference patent U.S. 12,351,641 claims are drawn to processes for producing a therapeutic IgG antibody in a Chinese hamster ovary (CHO) host cell expressing said therapeutic IgG antibody, wherein the process comprises culturing the CHO host cell in a production phase culture medium that is essentially free of glutamine, wherein the production phase culture medium comprises asparagine provided at a concentration in the range of 2.5 mM to 15 mM (see independent reference claims 1, 16, 21, and 26). The produced antibodies in the ’641 claims include pertuzumab (claim 1), omalizumab (claim 21), and ocrelizumab (claim 26), among other therapeutic IgG antibodies (see e.g. those of claim 16). Further, claim 2 of the ’641 patent recites that asparagine is provided at a concentration in the range of 7.5 mM to 15 mM and claim 3 specifically recites 10 mM asparagine. Claim 10 of the ’641 patent recites further comprising determining one or more of cell viability, culture longevity, specific productivity and final antibody titer following isolation. Claims 4, 19, 24, and 29 of the ’641 patent recites that host cell is a dhfr - CHO cell. Thus, the instant claims 41-43, 53, 54, 63, and 64 are deemed anticipated by the subject matter of the ’641 patent claims. Regarding claims 44 and 45, claims 11 and 12 of the reference application recite identical concentrations of aspartic acid. Regarding claims 46 and 47, claims 13 and 14 of the reference application recite identical concentrations of glutamate. Regarding the instant claim 48, reference claim 15 recites that aspartic acid is at a concentration of 10 mM, that glutamate is at a concentration of 1 mM, while claim 3 recites that the concentration of asparagine is 10 mM. Based on the encompassed subject matter of the reference patent claims, the instantly claimed combination is not patentably distinct from the compositions disclosed therein. Regarding the instant claims 49-52, claims 5-8 of the reference application recite that: the production medium is serum-free; the production culture medium comprises one or more ingredients selected from the group consisting of 1) an energy source; 2) essential amino acids; 3) vitamins; 4) free fatty acids; and 5) trace elements; the production culture medium additionally comprises one or more ingredients selected from the group consisting of: 1) hormones and other growth factors; 2) salts and buffers; and 3) nucleosides; and the production phase is a batch or fed batch culture phase. Regarding the instant claim 54, claim 1 of the reference patent recites that the produced polypeptide is a therapeutic IgG antibody. Regarding claim 55, the reference claims do not explicitly recite that the antibody or antibody fragment is chimeric, humanized or human, however, examination of the encompassed therapeutic antibodies, based on well-known knowledge in the art and disclosures of the reference specification, would indicate that one or more of the recited specific antibodies are human or humanized (i.e. they recognize human antigens for therapeutic purposes). The claimed subject matter would have been obvious over the specific embodiments of the reference patent. Regarding the instant claim 56, the reference claims recite that the produced therapeutic antibody is can be, inter alia , an anti-CD20 antibody (e.g. also see ocrelizumab as in reference claim 26), a HER dimerization inhibitor (HDI) antibody; a HER2 binding antibody (e.g. pertuzumab as in reference claim 1), or an anti-CD4 antibody. Therefore, claim 56, as well as claims 57 and 58, are found unpatentable over the claims of the reference application. For at least these reasons, claims 41-58 are rejected on the grounds of nonstatutory double patenting as being unpatentable over the subject matter of US 12,351,641. Conclusion No claims are allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm 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. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anand Desai can be reached at 571-272-0947. 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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. /A.T.M./Examiner, Art Unit 1655 /ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655 Application/Control Number: 18/820,925 Page 2 Art Unit: 1655 Application/Control Number: 18/820,925 Page 3 Art Unit: 1655 Application/Control Number: 18/820,925 Page 4 Art Unit: 1655 Application/Control Number: 18/820,925 Page 5 Art Unit: 1655 Application/Control Number: 18/820,925 Page 6 Art Unit: 1655 Application/Control Number: 18/820,925 Page 7 Art Unit: 1655 Application/Control Number: 18/820,925 Page 8 Art Unit: 1655 Application/Control Number: 18/820,925 Page 9 Art Unit: 1655 Application/Control Number: 18/820,925 Page 10 Art Unit: 1655 Application/Control Number: 18/820,925 Page 11 Art Unit: 1655 Application/Control Number: 18/820,925 Page 12 Art Unit: 1655 Application/Control Number: 18/820,925 Page 13 Art Unit: 1655 Application/Control Number: 18/820,925 Page 14 Art Unit: 1655 Application/Control Number: 18/820,925 Page 15 Art Unit: 1655 Application/Control Number: 18/820,925 Page 16 Art Unit: 1655 Application/Control Number: 18/820,925 Page 17 Art Unit: 1655 Application/Control Number: 18/820,925 Page 18 Art Unit: 1655 Application/Control Number: 18/820,925 Page 19 Art Unit: 1655 Application/Control Number: 18/820,925 Page 20 Art Unit: 1655 Application/Control Number: 18/820,925 Page 21 Art Unit: 1655 Application/Control Number: 18/820,925 Page 22 Art Unit: 1655 Application/Control Number: 18/820,925 Page 23 Art Unit: 1655 Application/Control Number: 18/820,925 Page 24 Art Unit: 1655 Application/Control Number: 18/820,925 Page 25 Art Unit: 1655 Application/Control Number: 18/820,925 Page 26 Art Unit: 1655
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