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 .
Election/Restrictions
Applicant’s election without traverse of Group 1 (a modified mammalian cell), Genus A (the gene combination is MYC, BAX, BAK, SIRT-1 and ICAM-1), and Genus B (the cell line is CHO) in the reply filed on 12/15/2025 is acknowledged.
Claim 8 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/15/2025.
Status of Claims
Claims 1-8 are currently pending; claims 9-21 have been cancelled.
Claims 1-7 are under consideration, as claim 8 is withdrawn.
Priority
Acknowledgment is made of applicant’s claim for benefit under 35 U.S.C. 119(e) of Provisional application No. 63/332,531, filed on 04/19/2022. The present application and all claims are being examined with an effective filing date of 04/19/2022. In future actions, the effective filing date may change due to amendments or further review of priority documents.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/02/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Objections
Claim 6 is objected to because of a typographical error, in reciting “expression of MAY”.
The claim should be amended to recite “expression of MYC”.
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 applicant regards as his invention.
Claim 6 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.
Claim 6 recites the limitation "the stable introduction of one or more nucleic acids encoding a heterologous protein”, for which there is insufficient antecedent basis. Neither claim 1 nor claim 6 previously introduce a stable introduction of nucleic acids or a heterologous protein. Additionally, it is unclear whether the recited introduction of one or more nucleic acids imposes any structural limitation on the claimed mammalian cell, whether it is intended to cause the reduced or eliminated expression of the recited genes, or whether such introduction is merely temporally or descriptively related to the claimed cell. As written, it is unclear whether claim 6 meaningfully further limits claim 1.
Due to the significant lack of clarity discussed above, claim 6 is not amenable to meaningful examination over the prior art. Accordingly, further examination of claim 6 with respect to the prior art is deferred pending clarification from the Applicant.
Appropriate response and clarification are requested.
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.
Claims 1-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted that MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow. Claim 1 has been broadly interpreted as a genus of modified mammalian cells, wherein expression of the MYC gene and one or more of the BAK, BAX, SIRT-1, and ICAM-1 genes has been reduced or eliminated (by any mechanism).
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) states that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions 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…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus, or by the establishment of ‘a reasonable structure-function correlation.’"
In the instant case, the claims broadly encompass a genus of mammalians cells modified wherein expression of MYC, BAX, BAK, ICAM-1, and/or SIRT-1 is reduced or eliminated. Such claim language reasonably includes multiple distinct mechanisms for achieving reduced expression, including but not limited to gene knockout, gene knockdown, transcriptional repression, post-transcriptional silencing, or other regulatory and cis or trans approaches. However, the specification demonstrates possession only of a single, highly specific example – namely CRISPR-Cas9 mediated gene knockouts in CHO host cells. While the specification provides working examples and experimental data involving CHO cells, including CHO cells comprising various combinations of reduced MYC, BAX, BAK, ICAM-1, and SIRT-1 expression, the disclosure is limited exclusively to targeted gene disruption, as exemplified by the RNP-based CRISPR Cas9 knockout experiments, and to TI CHO host cells. The specification does not describe or exemplify alternative means of reducing expression, nor does it provide guidance or data demonstrating that such alternative approaches were possessed by the inventors at the time of filing. Likewise, the specification does not describe or exemplify the claimed genetic modifications in any other mammalian cell type, nor does it provide experimental data, prophetic examples, or technical guidance demonstrating that the claimed modifications would function similarly in non-CHO mammalian cells.
Moreover, the specification does not set forth a structural or functional rationale explaining why the effects observed in CHO cells—such as altered cell cycle progression, reduced aggregation, enhanced viability, or increased recombinant protein production—would be expected to occur across mammalian cells generally. Nor does the specification explain why such effects would be expected to arise from reduced expression achieved through mechanisms other than the specific CRISPR-Cas9 mediated gene knockouts disclosed in the examples. Absent such disclosure, the specification does not demonstrate that the inventors were in possession of the claimed invention for mammalian cells as a genus.
Accordingly, because the specification describes only CHO cell embodiments and does not reasonably convey possession of the claimed invention across the full scope of modified mammalian cells, claims 1-7 lack adequate written description under 35 U.S.C. §112(a).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Moreno de Alboran et al. (Analysis of C-MYC Function in Normal Cells via Conditional Gene-Targeted Mutation, Immunity, Jan 2001, Vol. 14, pg. 45–55, herein “Moreno”, cited in PTO-892), Kumar et al. (Proliferation control strategies to improve productivity and survival during CHO based production culture, Cytotechnology (2007) 53:33–46, cited in PTO-892), and Misaghi et al. (WO2021262783, cited in the IDS).
Kumar et al. teaches that “cells arrested at the end of G1-phase of cell cycle are metabolically more active and bigger in size than non-arrested cells”. Kumar further teaches that “the G1-phase of the cell cycle is considered the ideal time for increased production of recombinant proteins and G1 arrest has been used to increase the productivity in a number of commercially relevant cell lines such as hybridomas and CHO (pg. 34, left column).
Moreno teaches that Myc proteins are “members of a basic region/helix-loop-helix/leucine zipper (bHLHZip) transcription factor family and have been implicated in the regulation of cellular proliferation, differentiation, and apoptosis” (pg. 45, Introduction). Moreno further teaches that in fibroblasts, inactivation of myc results in reduced proliferation, increase in accumulation of cells in the G0/G1 stage of the cell cycle, and decrease of cells in S phase. Likewise, accumulation of B cells at the G0/G1 stage of the cell cycle was observed when c-myc is inactivated in B lymphocytes (pg. 46, bottom left-top right). Importantly, Moreno also teaches that such cells remain functional, disclosing “anti-CD40 treated c-myc deficient B cells express early activation markers” (pg. 50, Fig. 4).
Misaghi et al. teaches genetically modified mammalian cell lines, including CHO cells, with resistance to apoptosis in order to provide high productivity and robust performance in the production of a “product of interest”, including a recombinant polynucleotide and/or recombinant polypeptide. Specifically, Misaghi et al. teaches said cells comprising stable loss of function or attenuation of function mutations in BAX and BAK genes, further teaching that deletion in BAX and BAK genes results in reduction of undesired effects associated with undesired apoptotic activity, e.g., reduced viability and productivity of the cells (Specification, pg. 2-3). Misaghi et al. discloses BAX/BAK double knock out clones for antibody production (see all figures). Misaghi et al. also teaches the cell line comprises a polynucleotide encoding a product of interest, that the product of interest may be an antibody, wherein the antibody may be a multispecific antibody (pg. 3). Furthermore, Misaghi et al. teaches wherein the polynucleotide may be integrated in the cellular genome of the cell at a targeted location, into one or more pre-determined (targeted) recombinant recognition sites, such as LoxFas (pg. 33-34, 5.3 “Cell Lines”), correlating to the “target integration landing site” recited in claim 4.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, the teachings of Kumar et al. that cells arrested at the end of the G1 phase are larger, more metabolically active, and represent the ideal phase for increased recombinant protein production, and the teachings of Moreno that inactivation of MYC results in reduced proliferation and accumulation of cells in the G0/G1 phase of the cell cycle while maintaining cellular functionality, combined with the teachings of Misaghi et al. that genetically modified CHO cells, comprising double knockouts of the BAX and BAK genes, enables high productivity, increased cell viability and robust performance during recombinant protein production, including the production of multispecific antibodies from stably integrated heterologous polynucleotides at targeted genomic integration sites, would have motivated a person of ordinary skill in the art to further modify the mammalian cells of Moreno to knockout BAK and BAX genes, for the benefit of further improving recombinant protein production. There is a reasonable expectation of success because Kumar et al. teaches that cells arrested at the G1 phase are ideal and desirable for increased recombinant protein production, and Misaghi et al. demonstrates the successful recombinant production of antibodies in BAX and BAK double knockout CHO cells. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Thus, claims 1, 3-5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Moreno, Kumar et al., and Misaghi et al.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al., Moreno, and Misaghi et al., as applied to claim 1 above, further in view of Auslaender and Oswald (WO2020260327, herein “Auslaender”, cited in the IDS), and Louie et al. (Endothelial intercellular cell adhesion molecule 1 contributes to cell aggregate formation in CHO cells cultured in serum-free media. Biotechnol Progress. 2020; 36:e29251, cited in PTO-892).
The teachings of Kumar et al., Moreno and Misaghi et al. as they apply to claim 1, has already been discussed above. Briefly, Kumar et al. teaches that cells arrested at the G1 phase of the cell cycle are ideal for recombinant protein production, while Moreno teaches fibroblasts and B cells undergoing c-myc inactivation accumulate at the G0/G1 stage of the cell cycle and remain functional. Misaghi et al. teaches BAX and BAK double knockout CHO cells exhibit high productivity, increased cell viability and robust performance during recombinant protein production.
Auslaender teaches recombinant mammalian cells, including CHO cells, in which endogenous SIRT-1 has been reduced or completely knocked out. Auslaender further teaches that reduction or knockout of SIRT-1 results in improved recombinant productivity (“increased productivity for heterologous polypeptides”), reduces lactate production by the cells, and a reduction in viability decline at the end of fed-batch fermentation (“extended high viability levels during cultivation”) (Abstract, and Specification, pg. 3).
Louie et al. teaches that ICAM-1 promotes cell aggregation in suspension-cultured CHO cells, resulting in reduced viability. Louie et al. further teaches “knocking out (KO) the ICAM-1 gene (pg. 3, left column) significantly decreased cell aggregate formation in the culture media without anti-cell-aggregation reagent” (Abstract).
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, the teachings of Auslaender, that knockout of endogenous SIRT-1 in CHO cells increases productivity of heterologous polypeptides, reduces lactate accumulation, and extends cell viability, would have motivated a person of ordinary skill in the art to further modify the modified cells obvious by Kumar et al., Moreno and Misaghi et al., to further improve recombinant protein production and increase cell viability by reducing or eliminating expression of the SIRT-1 gene. Said practitioner would further be motivated to further modify said obvious cell, to reduce or eliminate ICAM-1 expression, in view of Louie et al.’s disclosure that ICAM-1 promotes cell aggregation in cultured CHO cells. There is a reasonable expectation of success because each of the applied references independently demonstrates successful recombinant protein expression in CHO cells following modification of the respective claimed genes, and the combined modifications address complementary and non-conflicting cellular limitations relating to apoptosis resistance, metabolic efficiency, aggregation control, and cell-cycle optimization. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Thus, claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al., Moreno, and Misaghi et al., further in view of Auslaender and Louie et al.
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 1-2, 4 and 6-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-7 of copending Application No. 18966005 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘005 claims drawn to a modified CHO or HEK cell wherein the transcriptional activity of the genes encoding procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 (PLOD1), procollagen- lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) and procollagen-lysine,2-oxoglutarate 5- dioxygenase 3 (PLOD3) has been permanently reduced, wherein further the transcriptional activity of one or more or all of the MYC gene or/and the BAX gene, or/and the BAK gene, or/and ICAM-1 gene, or/and the SIRT-1 genes has been permanently reduced, anticipate and/or render obvious instant claims 1-2, 4 and 6, drawn to a modified mammalian cell wherein the expression of the MYC gene and one or more of the BAK, BAX, SIRT-1 and ICAM-1 genes has been reduced or eliminated.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18919812 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘812 claims, drawn to a modified Chinese Hamster Ovary (CHO) cell where, prior to the modification, the CHO cell comprises two or more endogenous retrovirus (ERV) loci selected from:(a) CHERV-lb (Genbank Accession No. MN527960, SEQ ID NO. 8);(b) CHERV-2g (Genbank Accession No. MN527961, SEQ ID NO. 9);(c) ETC109F (30021-39247 of SEQ ID NO. 10);(d) CHERV-3g (Genbank Accession No. MN527962, SEQ ID NO. 11); and(e) an ERV locus comprising a sequence having at least 90% identity to any one of (a)-(d), and where the modification comprises inactivation of two or more of the ERV loci of (a)-(e), wherein the modified cell is generated from a recombinant cell that expresses a recombinant product of interest, wherein the recombinant product of interest is encoded by an exogenous nucleic acid sequence integrated in the cellular genome of the CHO cell at one or more targeted locations, wherein the targeted location is at least about 90% homologous to a sequence of a portion of the contig sequence of one of the contigs NW_006874047.1, NW_006884592.1, NW_006881296.1, NW_003616412.1, NW_003615063.1, NW_006882936.1, and NW_003615411.1, or to a sequence selected from SEQ ID Nos. 1-7, wherein the modified CHO cell comprises gene knock-outs selected from: a) BAX; BAK; ICAM-1; GGTA1; CMAH; LPL; LPLA2; and PPT1; b) BAX; BAK; ICAM-1; SIRT-1; GGTA1; CMAH; LPL, LPLA2; and PPT1; c) BAX; BAK; ICAM- ACTIVE 124492715.1 102 1; SIRT-1; MYC; GGTA1; CMAH; LPL; LPLA2; and PPT1; d) BAX; BAK; ICAM-1; SIRT-1; MYC; anticipate and/or render obvious instant claims 1-2, 4-7, drawn to a modified mammalian cell wherein the expression of the MYC gene and one or more of the BAK, BAX, SIRT-1 and ICAM-1 genes has been reduced or eliminated.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-13 of copending Application No. 18489274 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘274 claims, drawn to a modified mammalian cell, wherein the cell is modified to reduce or eliminate the expression of one or more endogenous products relative to the expression of the endogenous products in an unmodified cell, wherein the one or more endogenous products:(a) promotes apoptosis of the modified cell during cell culture; (b) promotes clumping and/or aggregation of the modified cell during cell culture; (c) is not essential for the growth, survival, and/or productivity of the modified cell during cell culture;(d) promotes non-human glycosylation patterns in a recombinant protein product produced by the modified cell during cell culture; (e) can co-purify with the product of interest produced by the modified cell during cell culture;(f) promotes branched chain amino acid catabolism; and/or (g) requires removal by purification for product quality and/or safety reasons, wherein the cell is modified to reduce or eliminate the expression of one or more endogenous products relative to the expression of the endogenous products in an unmodified cell, wherein the one or more endogenous products is selected from endogenous virus-like particles such as retrovirus- like particles (RVLPs) and/or the endogenous protein group consisting of: BCL2 Associated X, Apoptosis Regulator (BAX); BCL2 Antagonist/Killer 1 (BAK); Intercellular Adhesion Molecule 1 (ICAM-1); Protein Kinase R-like ER Kinase (PERK); Sirtuin 1 (SIRT-1); MYC Proto-Oncogene, BHLH Transcription Factor (MYC); Glycoprotein Alpha- Galactosyltransferase 1 (GGTA1); Cytidine Monophosphate-N-Acetylneuraminic Acid Hydroxylase (CMAH); Branched Chain Keto Acid Dehydrogenase El alpha subunit (BCKDHA); Branched Chain Keto Acid Dehydrogenase El beta subunit (BCKDHB); Lipoprotein lipase (LPL); Phospholipase A2 group XV (LPLA2); Palmitoyl-protein thioesterase 1 (PPT1); and Lipase A (Lysosomal acid lipase/cholesteryl ester hydrolase, Lipase) (LIPA), anticipate and/or render obvious instant claims 1-2, 4-7 drawn to a modified mammalian cell wherein the expression of the MYC gene and one or more of the BAK, BAX, SIRT-1 and ICAM-1 genes has been reduced or eliminated.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8-10, 14 and 13 of copending Application No. 17483587 (reference application) in view of Auslaender (WO2020260327, cited in the IDS).
Copending application ‘587 claims a method for producing a heterologous polypeptide comprising the steps of a) cultivating a CHO cell comprising a deoxyribonucleic acid encoding the heterologous polypeptide, and b) recovering the heterologous polypeptide from the cell or the cultivation medium, wherein the expression of at least the endogenous gene MYC has been reduced or knocked- out in said CHO cell and the expression of the heterologous polypeptide is increased. Application ‘587 further claims wherein the heterologous polypeptide is an antibody. The copending application does not teach wherein expression of one or more of the BAK, BAX, SIRT-1, and ICAM-1 genes has been reduced or eliminated.
Auslaender teaches recombinant mammalian cells, including CHO cells, in which endogenous SIRT-1 has been reduced or completely knocked out. Auslaender further teaches that reduction or knockout of SIRT-1 results in improved recombinant productivity (“increased productivity for heterologous polypeptides”), reduces lactate production by the cells, and a reduction in viability decline at the end of fed-batch fermentation (“extended high viability levels during cultivation”) (Abstract, and Specification, pg. 3). Auslaender further teaches wherein the host cell comprises an integrated landing site (pg. 31) and wherein the recombinant polypeptide is an antibody, including multispecific antibodies (pg. 5 and 20).
Before the effective filing date of the claimed invention, the teachings of Auslaender that reduction or knockout of SIRT-1 in CHO cells results in improved recombinant productivity of heterologous polypeptides (including antibodies) would have motivated a person of ordinary skill in the art to modify the claimed method of application ‘587 to also knockout the SIRT-1 gene for improved production of the heterologous polypeptide. There is a reasonable expectation of success because Auslaender independently demonstrates successful recombinant protein expression in CHO cells following modification of said cell by completely knocking out SIRT-1, resulting in improved recombinant productivity and cell viability. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is in condition for allowance.
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/NAGHMEH NINA MOAZZAMI/ Examiner, Art Unit 1652
/RICHARD G HUTSON/ Primary Examiner, Art Unit 1652