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 .
DETAILED ACTION
Application Status
This application is a 371 of PCT/US2022/053772, filed on 06/21/2024.
Claims 1, 3, 11, 20, 23, 27, 31, 34-35, 51, 55, 57, 62, 68, 70, 80, 82, and 84-85 are currently pending.
The preliminary amendment filed on 05/26/2026, amending claims 1, 11, 20, 57, and 70, canceling claims 2, 4-10, 12-19, 21-22, 24-26, 28-30, 32-33, 36-50, 52-54, 56, 58-61, 63-67, 69, 71-79, 81, and 83, and adding new claims 84-85 is acknowledged.
Election/Restriction
Applicant's election without traverse of Group I, Claims 1, 3-4, 11, 20, 23, 27, 31, 34-35, 51, and 55, drawn to a microbial cell for producing one or more lactones, the microbial cell expressing an enzyme having fatty acid hydroxylase activity, wherein the microbial cell is engineered relative to a parent strain to have one or more modifications selected from: (a) a decrease in expression and/or activity of one or more enzymes involved in fatty acid activation and degradation, (b) a decrease in expression and/or activity of one or more 3-oxidation and/or peroxisome enzymes; (c) a modification in expression and/or activity of one or more lipases; (d) a decrease in expression and/or activity of o-oxidation enzymes; and (e) a decrease in expression and/or activity of one or more acyl-CoA synthetase enzymes;(f) an increase in metabolic NADPH supply; (g) a decrease in expression and/or activity of one or more neutral lipid biosynthesis enzymes; and/or (h) a decrease in expression and/or activity of one or more of citric acid cytoplasmic exporter, and one or more NADPH dependent aldehyde reductases, in the response filed on 05/26/2026 is acknowledged.
Claims 57, 62, 68, 70, 80, 82, and 84-85 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicants request for rejoinder is noted. However, current claims of elected Group I are not allowable at this time. When Group I would be allowable, rejoinder request would be evaluated at that time.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1, 3-4, 11, 20, 23, 27, 31, 34-35, 51, and 55 are present for examination.
Priority
Acknowledgement is made of applicants claim for priority of US Provisional application 63/293,357, filed on 12/23/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/21/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is considered by the examiner. The signed copy of 1449 is enclosed herewith.
Drawings
Drawings submitted on 06/21/2024 are accepted by the Examiner.
Specification objections
The disclosure is objected to because of the following informalities:
Specification The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 24). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code.
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.
See MPEP 2173.05(s), which states:
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).”
Claim 11 is rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 11 is indefinite in the recitation of Tables…..or figures in the claims (see, claim 11) which renders the claims indefinite and not permitted at all unless a special circumstances. Clarification and correction is required.
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.
A. Written Description
Claims 1, 3-4, 11, 20, 23, 27, 31, 34-35, 51, and 55 are rejected under 35 U.S.C. 112(a), 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is directed to a variant of a microbial cell for producing one or more lactones, the microbial cell expressing an enzyme having fatty acid hydroxylase activity and comprising a cytochrome P450 domain that is at least 80% identical to amino acids 1 to 461 of SEQ ID NO: 1 and a cytochrome P450 reductase (CPR) domain that is at least 80% identical to a sequence selected from SEQ ID NOS: 53, 57, and 58; wherein the microbial cell is engineered relative to a parent strain to have one or more modifications selected from: (a) a decrease in expression and/or activity of one or more enzymes involved in fatty acid activation and degradation, (b) a decrease in expression and/or activity of one or more p-oxidation and/or peroxisome enzymes; (c) a modification in expression and/or activity of one or more lipases; (d) a decrease in expression and/or activity of co-oxidation enzymes; and (e) a decrease in expression and/or activity of one or more acyl-CoA synthetase enzymes;(f) an increase in metabolic NADPH supply; (g) a decrease in expression and/or activity of one or more neutral lipid biosynthesis enzymes; and (h) a decrease in expression and/or activity of one or more of citric acid cytoplasmic exporter, and one or more NADPH dependent aldehyde reductases.
The Court of Appeals for the Federal Circuit has held that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).
Thus, Claim is drawn to any variant of a microbial cell for producing one or more any kind of lactones, the microbial cell expressing any enzyme having any fatty acid hydroxylase activity derived from any sources having no structural feature, and comprising any cytochrome P450 domain that is at least 80% identical to amino acids 1 to 461 of SEQ ID NO: 1, i.e., 20% non-identity, and any cytochrome P450 reductase (CPR) domain that is at least 80% identical to a sequence selected from SEQ ID NOS: 53, 57, and 58, i.e., 20% non-identity of any cytochrome P450 domain, and any cytochrome P450 reductase (CPR) domain, used to make a variant microbial cell tp produce lactones, i.e., 20% non-identity to SEQ ID NO: 1, and SEQ ID NO: 53 of the that encompasses many variant cytochrome P450 domain having hydroxylase activity, and any cytochrome P450 reductase (CPR) domain enzymes derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, i.e. No Structure-Function correlation, which is required to fulfill the Written Description (WD) requirement.
As discussed in the written description guidelines the Written Description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Furthermore, the genus of polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides are adequately described by the disclosure of the structures of prior art. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., (2003) highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer, it is difficult to state criteria for successful prediction of function, since function is a vague concept. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (1999) teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev L., (2002) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Claims are drawn to very broadly any variant of a microbial cell for producing one or more any kind of lactones, the microbial cell expressing any enzyme having any fatty acid hydroxylase activity derived from any sources having no structural feature, and comprising any cytochrome P450 domain that is at least 80% identical to amino acids 1 to 461 of SEQ ID NO: 1, i.e., 20% non-identity, and any cytochrome P450 reductase (CPR) domain that is at least 80% identical to a sequence selected from SEQ ID NOS: 53, 57, and 58, i.e., 20% non-identity of any cytochrome P450 domain, and any cytochrome P450 reductase (CPR) domain, used to make a variant microbial cell tp produce lactones, i.e., 20% non-identity to SEQ ID NO: 1, and SEQ ID NO: 53 of the that encompasses many variant cytochrome P450 domain having hydroxylase activity, and any cytochrome P450 reductase (CPR) domain enzymes derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, whose structures are not fully described in the specification. No information, beyond the characterization of variant lipases enzymes has been provided, which would indicate that applicants had possession of the claimed genus. The specification does not contain sufficient disclosure of the structure with function of all the any cytochrome P450 hydroxylase domain, and any cytochrome P450 reductase (CPR) domain enzymes, within the scope of the claimed genus. The genus of polypeptides claimed is a large variable genus including many mutants, variant and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated enzymes (variant hydroxylase and reductase) within the scope of these claims. The specification discloses the structure of only few representative species of the claimed genus, which is insufficient to put one of skill in the art in possession of the attributes and features of all species within the claimed genus. Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
The prior arts of interest: i) Maseme et al. (CYP505E3: A Novel Self-Sufficient w-7 In-Chain Hydroxylase. Angew. Chem. Int. Ed. 2020, 59, 10359-10362), and ii) Smit et al. (Process for the modification of the alkanes, fatty acids, and fatty alcohols. US 2020/0248213A1, publication 08/06/2020).
Conclusion
Status of the claims:
Claims 1, 3-4, 11, 20, 23, 27, 31, 34-35, 51, and 55 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Primary Patent Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656
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