DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a DIV of 16/917,099, filed 30 June 2020 now patent 11,718,864; which is a DIV of 15/762,345, filed 22 March 2018 now patent 10,738,334; which is a 371 of PCT/IB2016/055666 filed 22 September 2016; which claims benefit of 62/396,475 filed 19 September 2016 and claims benefit of 62/222,555 filed 23 September 2015.
Claim Status
Claims 1-69 were previously cancelled, claim 74 is newly canceled, claims 70-73 are currently amended, claims 75-76 are new, and claims 70-73 and 75-76 have been considered on their merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Withdrawn Rejections
The claim rejections under 102 and 103 have been withdrawn due to Applicant’s amendments to the claims.
Claim Interpretation
The second wherein clause of claim 70, directed to the reduction of the level of synthesis of growth and/or productivity inhibitors produced by the cell, starting at the last paragraph of the claim, reads as an inherent result of the cells expressing the exogenous wild-type genes. Therefore, if the cell comprises the genes, it would necessarily possess these properties. Thus, the wherein clause of claim 70 is not considered limiting.
Response to Arguments
Applicant’s arguments, see the remarks, filed 26 June 2026, with respect to the rejections under 35 U.S.C. 102 and 103 have been fully considered and are persuasive. Specifically, the amendment to the claims, wherein the two or more exogenous wild-type genes include at least one of Auh or Ivd. The art rejections of record have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Panzer, Duan, and Fan. Any relevant arguments directed to previously utilized references will be responded to following the new rejections below.
Regarding the request for consideration of the information directed to the parental applications found on page 6 of the remarks, each case is examined on its own merits. However, all previously considered parental applications/patents have been considered, as requested.
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 70 and 71 are rejected under 35 U.S.C. 103 as being unpatentable over Baumgartner et al. (J Clin Invest. 2001, February 2001, of record) as evidenced by Grünert et al. (Orphanet Journal of Rare Diseases 2012, published 29 May 2012, of record) and in view of Panzer et al. (US 2004/0115629 A1, published 17 June 2004) and Duan et al. (Frontiers in Bioscience, Landmark, 20, 796-813, January 1, 2015).
This is a new rejection, necessitated by Applicant’s amendments to the claims. A response to Applicant' s traversal follows the new rejection below.
Regarding claims 70 and 71, Baumgartner teaches the molecular basis of human 3-
methylcrotonyl-CoA carboxylase (MCC) deficiency, which is a disorder of leucine catabolism (Abstract). Baumgartner teaches cloning of MCCA and MCCB cDNAs and the organization of their structural genes (Abstract). MCCA and MCCB were later renamed MCCC1 (formerly MCCA) and MCCC2 (formerly MCCB), as evidenced by Grünert (Grünert, p. 1, Background). Baumgartner teaches cloning full-length human wild-type MCCA and MCCB cDNAs into pCR Blunt II TOPO (p. 497, Construction of wild-type and mutant human MCCA/B expression vectors). Baumgartner teaches transferring the wild-type and mutant MCCA and MCCB constructs into a mammalian expression vector, pTracer-CMV2 (claim 71) at the EcoR I site (p. 497, Construction of wild-type and mutant human MCCA/B expression vectors). Baumgartner teaches the human wild-type MCCA and MCCB cDNAs subclones were electroporated into a SV40T transformed reference CG2 or CG1 cell line, human lymphoblastoid cell lines, to measure MCC activity (p. 501, Expression of MCCA and MCCB alleles). The CG2 or CG1 cells comprising the MCCA and MCCB cDNAs subclones read as mammalian cells comprising both MCCC1 and MCCC2. Baumgartner teaches wild-type MCCA and MCCB alleles restored MCC activity to 43% and 53% of untransfected control fibroblasts, respectively (p. 501, Expression of MCCA and MCCB alleles and Table 3).
Baumgartner teaches mammalian cells comprising both MCCC1 and MCCC2, however, does not teach wherein the two or more exogenous wild-type genes include at least one of Auh or Ivd.
Panzer teaches enzymes involved in the metabolism of the carbon skeleton of amino acids include both isovaleryl CoA dehydrogenase (IVD) and β-methylcrotonyl CoA carboxylase (MCCC2) (para. [0183]).
Duan teaches the metabolic roles for L-leucine, an essential branched-chain amino acid (BCAA), go far beyond serving exclusively as a building block for de novo protein synthesis (Abstract). Duan teaches growing evidence shows that leucine regulates protein and lipid metabolism in animals, specifically, leucine activates the mammalian target of rapamycin (mTOR) signaling pathway, including the 70 kDa ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1) to stimulate protein synthesis in skeletal muscle and adipose tissue and to promote mitochondrial biogenesis, resulting in enhanced cellular respiration and energy partitioning (Abstract). Duan teaches protein synthesis is the major energy-consuming process in the cell. In particular, both mRNA translation and ribosomal biogenesis processes, which are strongly affected by the mTOR pathway, consume high levels of cellular energy (p. 796, Introduction). Duan teaches BCAAs, especially leucine, are essentially important for the regulation of protein metabolism; the underlying mechanisms include: 1) providing the precursors and metabolic substrates required for polypeptide biosynthesis, 2) regulating the release of endocrine hormones (such as insulin, insulin like growth factor-1(IGF-1)), and 3) modulating the mTOR signaling pathway responsible for protein synthesis (p. 798, Section 3.2).
Therefore, it would have been obvious to one of ordinary skill in the art to include at least Mccc2 and Ivd in a mammalian cell for the purpose of increased protein production with a reasonable expectation of success because Baumgartner teaches mammalian cells comprising both MCCC1 and MCCC2, thus, demonstrating to ability of mammalian cells to express more than one exogenous wild-type gene found in the same metabolic pathway. One would be motivated to include at least Mccc2 and Ivd in a mammalian cell for the purpose of increased protein production because Panzer teaches enzymes involved in the metabolism of the carbon skeleton of amino acids include both IVD and MCCC2. Additionally, Duan teaches BCAAs, especially leucine, are essentially important for the regulation of protein metabolism; the underlying mechanisms including providing the precursors and metabolic substrates required for polypeptide biosynthesis and modulating the mTOR signaling pathway responsible for protein synthesis.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Regarding Applicant’s arguments directed to the claim rejections under 102 as it pertains to Baumgartner, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn because Baumgartner does not teach wherein one or more of the exogenous wild-type genes including one of Auh or Ivd. However, the new rejection above addresses this new limitation.
Claims 72, 73, and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Baumgartner et al. (J Clin Invest. 2001, February 2001, of record) as evidenced by Grünert et al. (Orphanet Journal of Rare Diseases 2012, published 29 May 2012, of record) and in view of Panzer et al. (US 2004/0115629 A1, published 17 June 2004) and Duan et al. (Frontiers in Bioscience, Landmark, 20, 796-813, January 1, 2015) as applied to claims 70 and 71 above, and further in view of Kariko et al. (WO 2011/071931 A2, published 16 June 2011, of record).
This is a new rejection, necessitated by Applicant’s amendments to the claims. A response to Applicant' s traversal follows the new rejection below.
Regarding claims 72, 73, and 75, Baumgartner as evidenced by Grünert in view of Panzer and Duan do not teach wherein the cells is a CHO (claim 72) or HEK (claim 73) cell and wherein the cell expresses a recombinant protein (claim 75).
However, Kariko teaches a method for inducing a mammalian cell to produce a recombinant protein (claim 75), comprising contacting the mammalian cell with an in vitro-synthesized RNA molecule encoding the recombinant protein (p. 20, lines 3-5). Kariko teaches the encoded recombinant protein is MCCC1, MCCC2, or IVD, wherein, each recombinant protein represents a separate embodiment (p. 61, lines 15 and 27; p. 63, line 18; p. 65, lines 13-14).
Kariko evaluated the impact of unique UTRs on enhancement of ΨmRNA translational efficiency and compared both enhanced and not enhanced in vitro protein production using EPO mRNA (p. 108, lines 21-24). Kariko teaches the efficiency of protein production from each mRNA was assessed in multiple cell types to include the mammalian cell lines, HEK293 (claim 73) and CHO (claim 72) (p. 108, lines 26-26).
The protein expression example taught by Kariko was utilizing EPO mRNA and provided embodiments including encoded recombinant proteins MCCC1, MCCC2, or IVD, however, it would have been obvious to one of ordinary skill in the art to utilize the CHO or HEK cells to express the IVD and MCCC2 as suggested by the teachings of Baumgartner in view of Panzer and Duan with a reasonable expectation of success because both CHO and HEK cells are well-known in the art to commonly be utilized as producer cell lines. One of ordinary skill could modify the cells of Kariko to express more than one exogenous wild-type gene utilizing basic laboratory techniques. One would be motivated to utilize the CHO or HEK cells to express the IVD and MCCC2 as both cell lines are very-well known in the art and widely used in the biopharmaceutical industry.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Traversal
Regarding Applicant’s arguments directed to the claim rejections under 103 as it pertains to Kariko, have been fully considered and are persuasive. Therefore, the rejection has been withdrawn because Kariko does not teach mammalian cell comprising two or more exogenous
wild-type genes and wherein one or more of the exogenous wild-type genes including one of Auh or Ivd. However, the new rejection above addresses this new limitation.
Claims 76 is rejected under 35 U.S.C. 103 as being unpatentable over Baumgartner et al. (J Clin Invest. 2001, February 2001, of record) as evidenced by Grünert et al. (Orphanet Journal of Rare Diseases 2012, published 29 May 2012, of record) and in view of Panzer et al. (US 2004/0115629 A1, published 17 June 2004), Duan et al. (Frontiers in Bioscience, Landmark, 20, 796-813, January 1, 2015) Kariko et al. (WO 2011/071931 A2, published 16 June 2011, of record) as applied to claims 70-73 and 75 above, and further in view of Fan et al. (Biotechnology and Bioengineering, Vol. 112, No. 3, March 2015, IDS ref.).
This is a new rejection, necessitated by Applicant’s amendments to the claims.
Regarding claim 76, Baumgartner as evidenced by Grünert in view of Panzer, Duan, and Kariko do not teach where the recombinant protein or heterologous recombinant protein is an antibody.
However, Fan teaches the interplay between cell growth, cell metabolism, IgG synthesis and glycosylation and metabolic level will benefit bioprocess optimization (p. 522, 2nd column). Fan teaches Chinese hamster ovary (CHO) cells are extensively used for the production of recombinant antibodies as a result of their robust growth and the potential to produce non-immunogenic antibodies with glycosylation patterns similar to humans (p. 521, Introduction). Fan teaches producer CHO cells, amino acid metabolism as it relates to antibody production (p. 521, Introduction). Fan teaches CHO cells are widely used for antibody production and the monoclonal antibody mAb industry (p. 521, Introduction).
Therefore, it would have been obvious to one of ordinary skill in the art to utilize CHO cells to produce a recombinant antibody with a reasonable expectation of success because Fan teaches CHO cells are extensively used for the production of recombinant antibodies. One would be motivated to utilize CHO cells to produce a recombinant antibody because Fan teaches CHO cells are extensively used for the production of recombinant antibodies as a result of their robust growth and the potential to produce non-immunogenic antibodies with glycosylation patterns similar to humans and Kariko teaches a method for inducing a mammalian cell to produce a recombinant protein, comprising contacting the mammalian cell with an in vitro-synthesized RNA molecule encoding the recombinant protein wherein the encoded recombinant protein is MCCC1, MCCC2, or IVD. Additionally, Kariko teaches both mammalian cell lines HEK293 and CHO cells can be utilized to efficiently produce recombinant proteins of interest.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Relevant prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Pietiläinen et al. (PLoS Medicine, Vol. 5, Issue 3, March 2008)
Pietiläinen teaches genes common to the degradation of all BCAAs, i.e., leucine,
isoleucine and valine (BCAT2, BCKDHB) and those specific for the degradation of leucine (MCCC1, MCCC2, AUH).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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