CTNF 18/649,779 CTNF 75765 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claims 1-12 are under examination on the merits. Claim Objections 07-29-01 AIA Claim 1 is objected to because of the following informalities: the term “enzymatic” is spelled incorrectly . Appropriate correction is required. Claim Rejections - 35 USC § 112 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. 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. It is unclear how claim 6, is further limiting than its base claim 5, as both claims 5-6 have identical language. Claim 7 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. In claim 7, it is unclear what kind of enzymes are acyl-CoA hydrolase from E. coli, Haemophilus influenza etc. More specifically, applicant refers to said enzymes as alternatively a wild-type or homologous (see “or” language at the end of claim 7). It is unknown what alternative exists, if the claimed enzymes are neither “wild type” nor “homologous”. Claim 8 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. In claim 8, the hyperlink language recited at the end, is improper and indefinite (see 37 CFR section 1.57(d). Further, said claim refers to a series of enzymes by name and not by sequence composition and hence, the phrase “comprises at least one or more or all, of the conserved amino acid residues compared to the two of any …” recited in claim 8 fails to clarify the metes and bounds of acyl-CoA hydrolase amino acid sequences claimed because it is not possible to identify which specific conserved amino acids is referred to. Furthermore, for patentability purposes, said ambiguous homologous sequences cannot even be searched in the commercial and patent databases so that their contribution over the prior art can be assessed. 07-30-01 AIA 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 1-8, 10 and 12 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. Claim 1 (and its dependent claims 2-8, 10 and 12) are directed to a genus of Methylomicrobium host cells comprising a genus of heterologous hydrolases from all sources and species, wherein said genus is inadequately described in the disclosure, in terms of structure. The specification fails to teach how much structural homology exists across all acyl-CoA hydrolases from sources such as mammalian, fungal, bacterial, vertebrate etc. and at least how much structural homology among all said species (sources) is required to ensure successful incorporation of DNA encoding said enzymes with activity retention of expression product thereof, into the host cell claimed. Given the breadth of the heterologous enzymes (or DNA encoding them) claimed, some more information as to which regions of acyl-CoA hydrolase (or DNA encoding it) are critical such that said products can successfully be expressed in Methylomicrobium with activity retention, deems necessary that is currently lacking in the disclosure. All applicant provides are bacterial acyl-CoA hydrolases (or DNA encoding them, see claims 7-8 , which is a single species and this type of structural information is totally inadequate to fully describe the genus of Methylomicrobium host cell as claimed. Regarding claim 7-8, this lack of adequate structural information is even more serious. This is because in claim 7-8 (which are also indefinite, see above) applicant is claiming homologs of a series of bacterial acyl-CoA hydrolases (or DNA encoding them), having at least 70% identity to E. coli P0A8Z33, E. coli P0A8Y8 etc., (see [0055] of the specification) wherein once again, it is unknown which domains or regions therein are to be kept intact to ensure successful expression thereof with activity retention, in Methylomicrobium host cells. As applicant is aware, a single substitution in an enzyme amino acid sequence (or DNA encoding it) may result is its total lack of function and structural guidance in the case of homologs instantly claimed are extremely crucial and important. Since the host cells of claim 1 are inadequately described, a method of use thereof (see claim 12) is also inadequately described. In claim 10, applicant is referring to SEQ ID NO:1 substitution with a genus of amino acids with a bulky side chain. The specification does not describe the structural characteristics of these side chains. Given the fact that some bulky side chains of amino acids can be negatively or positively charged, or not at all and said side chains can be of different sizes, etc., some more structural information regarding said genus deems necessary that is currently lacking in the specification. All applicant has provided is phenylalanine (which is a single species ) and this kind of description also fails to satisfy the requirements of 112 first paragraph. Therefore, given the information provided and the breadth of instant claims, one of skill in the art cannot reasonably conclude that applicant had full possession of the invention before the effective filing of this application. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-21-aia AIA Claim (s) 1-8 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Shetty et al., “Shetty” (US2015/0315599, 11/2015) . Shetty in [0058], discloses that its invention relates to developing and using engineered and/or evolved methylotrophs capable of utilizing C1 compounds to produce a desired product. According to Shetty, its application provides for the engineering of a methylotroph, for example, Paracoccus denitrificans, Paracoccus versutus or Paracoccus zeaxanthinifaciens, or other organism suitable for commercial large-scale production of fuels and chemicals, that can efficiently utilize C1 compounds (such as methane , see [0059 and 0092]) as a substrate for growth and for chemical production provides cost-advantaged processes for manufacturing of carbon-based products of interest. The organisms can be optimized and tested rapidly and at reasonable costs. Said publication also provides guidance for the engineering of a methylotroph to include one or more additional or alternative pathways for utilization of C1 compounds to produce central metabolites for growth and/or other desired products. In [0104], Methylomicrobium alcaliphilum , is disclosed to be among the host cells which may be utilized by Shetty. Under “Production of Ethylene, Propylene, 1-Butene, 1,3-Butadiene, Acrylic Acid, Etc. as the Carbon-Based Products of Interest” section, in [0154], Shetty recites: in some embodiments, the engineered and/or evolved methylotroph of the present invention is engineered to produce propylene as the carbon-based product of interest and in [0155], reports that E.coli enzymes (or DNA encoding them) such as that corresponding to E.C. 3.1.2.20 (which inherently comprise short/long chain acyl-CoA hydrolases of this invention and are inherently a “homologue” of E. coli EntH of this invention) may be transformed or imported into said methylotrophs. Therefore, given the teachings of Shetty, before the effective filing of this application and depending on the source of methane substrate, one of ordinary skill in the art can reasonably envisage starting with the carbon based products production method of Shetty and utilize its Methylomicrobium alcaliphilum, which has been transformed or transfected with EC 3.1.2.20 enzyme family of acyl-CoA hydrolase (or DNA encoding it) to convert methane into one or more products disclosed in [0097] of Shetty; wherein said products include malonic acid, rendering this invention obvious. Finally, one of ordinary skill in the art has a reasonable expectation of success in converting methane with the engineered Methylomicrobium alcaliphilum of Shetty to produce malonic acid (or salts thereof) of Shetty because such procedures were fully established in the prior art, before the effective file of this application. With respect to claim 3-4, it appears that the specific strains of Methylomicrobium alcaliphilum claimed are not unique as they are not deposited with a specific deposit number under the terms of any treaty including Budapest treaty. Therefore, the patentably contribution of said strains over a generic Methylomicrobium alcaliphilum strain and a method of use thereof cannot be determined and hence, claims 3-4 are also added to this rejection. Allowable Subject Matter Claims 9 and 11 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. This is because, a genetically modified Methylomicrobium alcaliphilum strain comprising SEQ ID NO:1 with one or more substitutions (optionally with phenylalanine) at the following positions, namely P49, G51, A60, H89, H90 and I116 is novel and non-obvious. Further, the prior art fails to suggest such specifically claimed genetically modified Methylomicrobium strain. Hence, said modified strain is also non-obvious. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex. 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, Melenie L Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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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. /MARYAM MONSHIPOURI/Primary Examiner, Art Unit 1651 Application/Control Number: 18/649,779 Page 2 Art Unit: 1651 Application/Control Number: 18/649,779 Page 3 Art Unit: 1651 Application/Control Number: 18/649,779 Page 4 Art Unit: 1651 Application/Control Number: 18/649,779 Page 5 Art Unit: 1651 Application/Control Number: 18/649,779 Page 6 Art Unit: 1651 Application/Control Number: 18/649,779 Page 7 Art Unit: 1651 Application/Control Number: 18/649,779 Page 8 Art Unit: 1651 Application/Control Number: 18/649,779 Page 9 Art Unit: 1651
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