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: Election/Restrictions
Applicants’ election of Group I, claims 14-29, SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9; and as species capric acid, olive oil, oleic acid, decanal, E.coli BL21 and Saccharomyces cerevisiae with traverse for prosecution in reply filed on 05/04/2026 is acknowledged.
Applicants’ arguments regarding traversal have been considered, however examiner respectfully disagrees for the following reasons: (i) contrary to applicants’ arguments, the instant invention is rendered obvious by prior art (for details see 103 rejections below); and for reasons made of record in the restriction dated 03/04/2026 i.e., “a biotechnological method for producing at least one unsaturated aldehyde and its corresponding carboxylic acid and/or at least one saturated aldehyde and its corresponding carboxylic acid, wherein the method comprises providing at least one alpha-dioxygenase having an amino acid sequence according to SEQ ID NO: 1 or SEQ ID NO: 2, or an amino acid sequence having a similarity of 90% or more to SEQ ID NO: 1 or SEQ ID NO: 2, and at least one aldehyde dehydrogenase…; an amino acid sequence as the use of the indefinite article and “an” implies that there is more than one amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 and thus makes it unclear; is this recitation encompasses any subsequence within SEQ ID NO: 1 or SEQ ID NO: 2, as well as the full length sequence as claimed in Groups’ I-II does not share a corresponding special technical feature, because the prior art clearly teaches a biotechnological method for producing at least one unsaturated aldehyde and its corresponding carboxylic acid and/or at least one saturated aldehyde and its corresponding carboxylic acid, wherein the method comprises providing at least one alpha-dioxygenase and aldehyde dehydrogenase; see conversion of different fatty acids to fatty aldehydes utilizing alpha-dioxygenase and aldehyde dehydrogenase; applicants’ are directed to Buchhaupt et al., World J Microbiol Biotechnol., 2013, Vol. 29: 569-575 (see Abstract; Fig. 1, page 572; and entire document); and Kaehne et al., Appl Microbiol Biotechnol., 2011, Vol. 90: 989-995 (see Abstract; Fig. 1, page 990; Fig. 2-3, page 992; and entire document). Therefore, the shared technical feature of these claims and their method of use, does not constitute a special technical feature as defined in PCT Rule 13.2 as it is not a feature which defines a contribution of the claimed invention makes over the prior art”. Furthermore, applicants’ have not provided any arguments for species election and therefore “The election of the species may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species.
Should applicant traverse on the ground that the species are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the species to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103(a) of the other species”.
The examiner would like to reiterate that the applicants’ have elected Group I, claims 14-29, SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9; and as species capric acid, olive oil, oleic acid, decanal, E.coli BL21 and Saccharomyces cerevisiae and the other non-elected Group II and non-elected sequences and species of Group I cannot be rejoined with the elected Group I for reasons made of record in the Office-action dated 05/04/2026.
Additionally, if the examiner finds that the national stage application lacks unity of invention under 37 CFR 1.475, the examiner may in an Office Action require the applicant in the response to that action to elect an invention to which the claims shall be restricted. Such requirement may be made before any action at the discretion of the examiner. Examiner continues to maintain that “the PCT does not provide for multiple products or methods within single application”, therefore, unity of invention is lacking with regard to multiple products and multiple methods; see 37 CFR 1.475. 37 CFR 1.475 (d) also states: If multiple products, processes of manufacture or uses are claimed, the first invention of the category first mentioned in the claims of the application and the first recited invention of each other categories related thereto will be considered as the main invention in the claims, see PCT Article 17(3)(a) 1.47(c). 37 CFR 1.475(e) further states; the determination whether a group of invention is so linked as to form a single inventive concept shall be without regard to whether the inventions are claimed in separate claims or as alternative within a single claim. Thus, a comphrensive search of all inventions in Groups’ I-II, non-elected sequences and non-elected species would be a serious burden and contrary to applicants’ arguments, the requirement is still deemed proper and is therefore made FINAL.
Examiner would like to reiterate that the sequences in claims 14-16, 27 and 29 are considered to be unrelated, since each encoded polypeptide sequence claimed is structurally and functionally independent and distinct for the following reasons: each of these sequences has a unique polypeptide sequence identifier (SEQ ID NOs). As such the genus of polypeptide(s) sequences in each of claims 14-16, 27 and 29 are not considered to constitute a proper genus, and is therefore subject to restriction. Furthermore, in this case, a search of more than one of the polypeptide sequence(s) including the variants claimed in claims 14-16, 27 and 29 presents an undue burden on the Patent and Trademark Office due to the complex nature of the search in terms of computer time needed to perform the search and the subsequent analysis of the search results by the examiner. Searching structurally distinct molecules like polypeptide(s) having 90% sequence identity to the all the recited sequences in claims 14-16, 27 and 29 are not coextensive and the sequence search systems of the USPTO are at or near capacity, and search of multiple sequences in a significant number of patent applications is not practical, representing a real burden on the Office. Thus, a comphrensive search of each of the polypeptide(s) and their method of use would be a burden on the Office. The searches for any one invention are not required for and are not coextensive with the searches for any other invention, thereby creating an undue burden of search and examination. The results from a search of each of these inventions have different considerations with respect to the prior art. Burden Iies not only in the search of sequence databases, U.S. patents, but also in the search for Iiterature and foreign patents and in examination of the claim Ianguage and specification for compliance with the statutes concerning new matter, distinctness, written description and enablement. Thus, a comphrensive search of all inventions in Groups’ I-II would be a serious burden and contrary to applicants’ arguments, the requirement is still deemed proper and is therefore made FINAL.
Amended Claims 14-31 are pending in this application, elected Group I, claims 14-29, SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9; and as species capric acid, olive oil, oleic acid, decanal, E.coli BL21 and Saccharomyces cerevisiae, reading on the elected invention is now under consideration for examination; claims 30-31 and non-elected sequences and species of Group I 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/04/2026.
Priority
Acknowledgment is made of applicants’ claim for foreign priority under 35 U.S.C. 119(a)-(d). This application is a 371 of PCT/EP2022/073488 filed on 08/23/2022 and claims the priority date of EPO application 21193986.3 filed on 08/31/2021; however, no English translation of said foreign priority application has been provided. Therefore, the priority date for instant claims under consideration is deemed to be the filing date of 371 of PCT/EP2022/073488 filed on 08/23/2022.
Information disclosure statement
The information disclosure statement (IDS) submitted on 02/28/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statement is considered and initialed by the examiner.
Miscellaneous
A cursory review of the sequence search shows many applications filed by the current assignee of the instant application (SYMRISE AG) which disclose the polypeptides of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9. Furthermore, said SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9 correspond to different SEQ ID NOs designation in different applications. The examiner has made an earnest attempt at identifying double patenting issues in some of these applications as shown above. However, in view of the large number of applications already filed/matured into patents and the fact that new applications are being filed, the examiner hereby requests applicants’ collaboration in pointing out to the examiner those applications which could raise double patenting issues that the examiner has not been able to identify; specifically sequences with different SEQ ID NOs and having 100% sequence identity to SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9 of the instant application. Examiner would like to reiterate to applicants’, that it is their duty to disclose to the examiner any or all applications and allowed patents that either claims the same subject matter or related subject matter and those that are material to the prosecution of this instant application, such that double patenting can be avoided. Examiner urges the applicants’ to provide a list of their conflicting/related applications, identical to that claimed herein and a list of claims filed in other applications and take steps at their end to avoid double patenting.
Claims Objections
I. Claim 14 and claims 15-29 depending therefrom; claims 14-16, 27 and 29 are objected to, due to the following informality: Claims 14-16, 27 and 29 recites the phrase “… an amino acid sequence according to SEQ ID NO: 1, 5, and 9”, and “a nucleotide sequence according to SEQ ID NO: 3” as such, given that the claim language recites “… a nucleotide sequence”; and “an amino acid sequence”, it is deemed to encompass and read on polypeptides comprising “any two/dipeptide sequences of SEQ ID NO: 1, 3, 5, and 9 and having the recited activity. Examiner suggests amending the claim to recite “… the sequence”: and “the amino acid sequence” and “the polynucleotide sequence”. Appropriate correction is required. For examination purposes claims 14 and claims 15-29 depending therefrom are interpreted to encompass variants and mutants of the recited sequence(s).
II. Recitation of “and/or” in claims 14-16, 22-23 and 26 makes the claim indefinite, as it is not clear what limitations must be present. Correction and clarification is required. Examiner suggests amending the claim to recite “…or …”.
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.
I. Claim 14 and claims 15-29 depending therefrom 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 pre-AIA the applicant regards as the invention.
Claims 14-16, 27 and 29 recites the phrase “… an amino acid sequence according to SEQ ID NO: 1, 5, and 9”, and “a nucleotide sequence according to SEQ ID NO: 3”, as such, given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on polypeptides comprising “any two/dipeptide sequences of SEQ ID NO: 1 and having recited activity. Examiner suggests amending the claim to recite “the amino acid sequence” and “the polynucleotide sequence”. Appropriate correction is required. For examination purposes claims 14-29 depending therefrom are interpreted to encompass variants and mutants of the recited sequence(s). The scope of the claims are unclear, as such it is unclear how homologous/identical to the amino acid sequences of SEQ ID NOs: 1, 5, and 9; and the polynucleotide sequence of SEQ ID NO: 3 a sequence of interest must be to be included within the scope of the claims and furthermore, it is not clear whether a full-length or a partial fragments of SEQ ID NOs: 1, 3, 5 and 9 is encompassed within the scope of the claims.
II. Claims 14-16, 22-23 and 26 and claims 15-29 depending therefrom 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 pre-AIA the applicant regards as the invention; recitation of “and/or” in claims 14-16, 22-23 and 26 makes the claims indefinite, as it is not clear what limitations must be present. The metes and bounds of claims 14-16, 22-23 and 26 and claims 15-29 depending therefrom are not clear and thus, it would not be possible to one of ordinary skill in the art to define the metes and bounds of the desired patent protection. The rejection may be overcome by amending the claims to recite “… or …”. Correction and clarification is required. Examiner suggests amending the claim to recite “…or …”.
III. Claims 20-21 and 24-25 is indefinite in the recitation of “...derivatives”, because the term “...derivatives” adds variability to the scope and as written can include variability of structures and microorganisms of undefined genotype/phenotype; as written, one cannot determine if the term refers to ‘functions of several real variables’ of the claimed structures and microorganisms or ‘structural variables’ of claimed derivative. However, the extent of variability allowed is unclear and not defined on record. For examination purposes, no patentable weight will be given to the term. It is not clear to the examiner as to what the phrase “…derivative…” means in the context of the above claims, is this synonymous with “obtained from specific source or having specific structures? or does it include natural and man-made variants of unlimited/undefined structures thereof from any source? Furthermore, literally while the term “derived” means to “to isolate from or obtain from a source”, the above term could also mean “to arrive by reasoning i.e., to deduce or infer” or also mean “to produce from another substance”. Accordingly, claims 20-21 and 24-25 are rejected. Clarification and correction is required.
IV. Claim 23 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 pre-AIA the applicant regards as the invention.
Regarding claim 23, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
I. Claims 14-29 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 14-29, as interpreted are directed to encompass in the claimed method: an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29) as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1, 5 and 9 but any fragment/subsequence within SEQ ID NOs: 1, 5 and 9 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 5 and 9 (as in claims 1 and 3-12; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation); and a method of producing at least one aldehyde and its corresponding carboxylic acid (as in claims 14-29).
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, 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”. As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that 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.
In the instant case, there is no structure associated with function with regard to the members of the genus of polypeptides and the encoding polynucleotides in the claimed method i.e., an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29) as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1, 5 and 9 but any fragment/subsequence within SEQ ID NOs: 1, 5 and 9 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 5 and 9 (as in claims 1 and 3-12; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation); and a method of producing at least one aldehyde and its corresponding carboxylic acid (as in claims 14-29).
No information, beyond the characterization of an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 1 and having alpha-dioxygenase activity and encoded by the polynucleotide sequence of SEQ ID NO: 3 in a specific cellular context E. coli BL21 cells (see Example 1-3, pages 19-20 of the specification) has been provided by the applicants’, which would indicate that they had possession of the claimed genus of polypeptides and the encoding polynucleotides in the claimed method i.e., an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29) as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1, 5 and 9 but any fragment/subsequence within SEQ ID NOs: 1, 5 and 9 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 5 and 9 (as in claims 1 and 3-12; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation); and a method of producing at least one aldehyde and its corresponding carboxylic acid (as in claims 14-29).
The claimed genus of polypeptides and the encoding polynucleotides is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides and the encoding polynucleotides is adequately described by the disclosure of the structures of the amino acid sequence of SEQ ID NO: 1, 5, and 9 having associated activity/function, since one could use structural homology to isolate those encoding polypeptides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (i) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(ii) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340,) also 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 (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(iii) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Seffernick et al., (J. Bacteriol. 183(8): 2405-2410, 2001), teaches that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Broun et al., (Science 282:1315-1317, 1998), teaches that as few as four amino acid substitutions can convert an oleate 12-desaturase into a hydrolase and as few as six amino acid substitutions can transform a hydrolase to a desaturase.
As the claimed genera of polypeptides and encoding polynucleotides in the claimed method include widely variable structure and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
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. Applicants’ are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
II. Claims 14-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement, because the specification, while being enabling for the characterization of an isolated polypeptide comprising the amino acid sequence of SEQ ID NO: 1 and having alpha-dioxygenase activity and encoded by the polynucleotide sequence of SEQ ID NO: 3 in a specific cellular context E. coli BL21 cells (see Example 1-3, pages 19-20 of the specification), does not reasonably provide enablement for genus of polypeptides and the encoding polynucleotides in the claimed method i.e., an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29) as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1, 5 and 9 but any fragment/subsequence within SEQ ID NOs: 1, 5 and 9 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 5 and 9 (as in claims 1 and 3-12; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation); and a method of producing at least one aldehyde and its corresponding carboxylic acid (as in claims 14-29). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
The breadth of claims includes overly broad genus, applicants’ disclose no direction or guidance on how to design and make any polypeptide and the encoding polynucleotide of undefined structure having desired activity as noted in the breadth above. Thus, instant specification and prior art failed to describe how to make and use the claimed genus of polypeptides and the encoding polynucleotides sufficiently. Although, it is possible to display and create any protein structure in computer (in silico) and manipulate in any possible way, such as inserting any amino acid(s) into preexisting three-dimensional scaffold; the creation of desired catalytic/biologic activity in a solution is highly unpredictable.
According to MPEP § 2164.02: “All questions of enablement are evaluated against the claimed subject matter. The focus of the examination inquiry is whether everything within the scope of the claim is enabled.”; “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Nevertheless, not everything necessary to practice the invention need be disclosed. In fact, what is well-known is best omitted. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991). All that is necessary is that one skilled in the art be able to practice the claimed invention, given the level of knowledge and skill in the art. Further the scope of enablement must only bear a “reasonable correlation” to the scope of the claims. See, e.g., In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).”; and “As concerns the breadth of a claim relevant to enablement, the only relevant concern should be whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims. > AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003); < In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). See also Plant Genetic Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003) (alleged “pioneer status” of invention irrelevant to enablement determination).”
Instant claims are so broad such that, instant disclosure of instant specification and a general knowledge in the art are not commensurate with the scope of instant claims for one skilled in the art to make and use claimed invention without undue experimentation. As noted above, the breadth of instant claims encompass an overly broad genus of undefined structure including variants, mutants and homologs.
Therefore, taking into consideration the extremely broad scope of the claims, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, and the high degree of unpredictability of the prior art in regard to structural variability and its effect on function, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of genus of polypeptides and the encoding polynucleotides in the claimed method i.e., an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29) as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1, 5 and 9 but any fragment/subsequence within SEQ ID NOs: 1, 5 and 9 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 5 and 9 (as in claims 1 and 3-12; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation); and a method of producing at least one aldehyde and its corresponding carboxylic acid (as in claims 14-29); and a method of producing any protein, comprising any heterologous nucleic acid molecule of undefined and unlimited structures and encoding said protein of undefined and unlimited structures having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Although the claims are examined in the light of the specification, specification cannot be read into the claims, i.e., the limitations of the specification cannot be read into the claims (see MPEP 2111 R-5).
Claim Rejections: 35 USC § 103
The following is a quotation of 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 of this title, 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 negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 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.
Claims 14-29 are rejected under 35 U.S.C. 103(a) as being unpatentable over (i) Fraatz et al., (US 10,767,198 B2; PCT filed 11/28/2015, in IDS) and further in view of Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention, Riebel-Bommarius et al., (US 7,163,815 B2) disclosing a NAD(P)H oxidase having 100% sequence identity to SEQ ID NO: 5 of the instant invention and Vedai M., (UniProtKB/TrEMBL Accesion#Q56694, 06/20/2001) disclosing an aldehyde dehydrogenase having 100% sequence identity to SEQ ID NO: 9 of the instant invention (see provided sequence alignments).
Claims 14-29, as interpreted encompass a genus of polypeptides and the encoding polynucleotides in the claimed method i.e., an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29) as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1, 5 and 9 but any fragment/subsequence within SEQ ID NOs: 1, 5 and 9 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 5 and 9 (as in claims 1 and 3-12; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation); and a method of producing at least one aldehyde and its corresponding carboxylic acid (as in claims 14-29).
Regarding claims 14-26 and 28, the reference of Fraatz et al., (US 10,767,198 B2; PCT filed 11/28/2015) disclose method for producing branched aldehydes, the method comprising the following steps: (a) providing a culture of one or more fungi of the genus Conidiobolus and producing biomass containing branched carboxylic acids in free and/or bound form; (b) extracting the biomass from step (a) to produce a first intermediate containing free and/or bound carboxylic acids; (c) chemically, enzymatically or microbially hydrolyzing the bound carboxylic acids from the first intermediate; (d) treating the first intermediate with a reducing agent of a chemical nature to convert the free and/or bound carboxylic acids into the corresponding alcohols and separating one or more alcohols from interfering by-products and producing the chemically produced second intermediate containing these alcohols as a mixture or in enriched form; (e) treating the first intermediate with a reducing agent of a biological nature to convert the free and/or bound carboxylic acids into the corresponding aldehydes having the same number of carbon atoms compared to the free and/or bound carboxylic acids or into the corresponding aldehydes having a reduced number of carbon atoms by one compared to the free and/or bound carboxylic acids and producing the biologically produced second intermediate containing these aldehydes; (f) treating the chemically produced second intermediate with an oxidizing agent of a chemical nature to convert the free and/or bound alcohols into the corresponding aldehydes; and (g) removing interfering by-components from the fractions obtainable after step(s) (d) and/or (e) and/or (f) (see Abstract; Fig. 1, Fig. 6; and entire document), said method includes the use of polypeptides comprising an alpha-dioxygenase activity, an aldehyde dehydrogenase and a lipase (see Fig. 6, reproduced below).
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In said method, said aldehyde includes 12-methyltridecanal (col. 2, lines 5-36; and Fig.6); and raw materials of alcohols and aldehydes comprising C13-C18.E (Fig. 7A, 7C), microorganisms are a fungus including recombinant Saccharomyces sp., and a bacterium such as E. coli BL21 producing the enzymes of interest and a commercial source of lipase (see Examples: 3-12, cols. 8-14).
However, Fraatz et al., (US 10,767,198 B2; PCT filed 11/28/2015) are silent regarding an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29).
Regarding claims 14-16, 27 and 29, the following references disclose the functional and structural elements of the instant invention: Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention, Riebel-Bommarius et al., (US 7,163,815 B2) disclosing a NAD(P)H oxidase having 100% sequence identity to SEQ ID NO: 5 of the instant invention and Vedai M., (UniProtKB/TrEMBL Accesion#Q56694, 06/20/2001) disclosing an aldehyde dehydrogenase having 100% sequence identity to SEQ ID NO: 9 of the instant invention (see provided sequence alignments).
Therefore, using the indications of Fraatz et al., as a reference, it would have been easy for a person skilled in the art to use the polypeptides and the encoding DNA of Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention, Riebel-Bommarius et al., (US 7,163,815 B2) disclosing a NAD(P)H oxidase having 100% sequence identity to SEQ ID NO: 5 of the instant invention and Vedai M., (UniProtKB/TrEMBL Accesion#Q56694, 06/20/2001) disclosing an aldehyde dehydrogenase having 100% sequence identity to SEQ ID NO: 9 of the instant invention (see provided sequence alignments) to transform microorganisms of interest such as a fungus and use the generated transformant to produce aldehydes and corresponding carboxylic acids. As such, disclosure of Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention, Riebel-Bommarius et al., (US 7,163,815 B2) disclosing a NAD(P)H oxidase having 100% sequence identity to SEQ ID NO: 5 of the instant invention, clearly suggests to a skilled artisan to modify the teachings of Fraatz et al., and incorporate the enzymes from Walter et al, Riebel-Bommarius et al., and Vedai M., as claimed in the instant application in the claimed compositions and method of use as in the instant invention. One of ordinary skill in the art would have a reasonable expectation of success, since polypeptides having alpha-dioxygenase, aldehyde dehydrogenase, NADH oxidase and lipase, method of making and using said polypeptides are well known in the art.
Therefore, claims 14-29 are rejected under 35 U.S.C. 103(a) as being unpatentable over (i) Fraatz et al., (US 10,767,198 B2; PCT filed 11/28/2015, in IDS) and further in view of Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention, Riebel-Bommarius et al., (US 7,163,815 B2) disclosing a NAD(P)H oxidase having 100% sequence identity to SEQ ID NO: 5 of the instant invention and Vedai M., (UniProtKB/TrEMBL Accesion#Q56694, 06/20/2001) disclosing an aldehyde dehydrogenase having 100% sequence identity to SEQ ID NO: 9 of the instant invention (see provided sequence alignments).
Double Patenting rejection
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 14-29 are provisionally rejected on the ground of nonstatutory double patenting over amended claims 1-4, 6-10 and 16-17 (dated 05/14/2026) of co-pending Application No. 17/910,649 (US 2023/0407349 A1) and in view of Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention. This is a provisional double patenting rejection because the patentably indistinct claims have not in fact been patented.
The subject matter claimed in the instant application is fully disclosed in the referenced co-pending application and would be covered by any patent granted on that co-pending application since the referenced co-pending application and the instant application are claiming common subject matter, as follows: “a genus of polypeptides and the encoding polynucleotides in the claimed method i.e., an amino acid sequence according to SEQ ID NO: 1 having alpha-dioxygenase activity and any aldehyde dehydrogenase of undefined and unlimited structures (as in claims 14 and 16); a nucleic acid according to SEQ ID NO: 3 encoding said alpha-dioxygenase (as in claim 15); an amino acid sequence according to SEQ ID NO: 5 having NADH oxidase activity (as in claim 27); and an amino acid sequence according to SEQ ID NO: 9 having aldehyde dehydrogenase activity (as in claim 29) as such, the term “an amino acid sequence” in broadest reasonable interpretation encompasses not only SEQ ID NO: 1, 5 and 9 but any fragment/subsequence within SEQ ID NOs: 1, 5 and 9 due to the recitation of indefinite article “an”; given that the claim language recites “an amino acid sequence”, it is deemed to encompass and read on “any two/dipeptide sequences of SEQ ID NOs: 1, 5 and 9 (as in claims 1 and 3-12; also see claims objections and 35 U.S.C. 112(b), rejection above for claim interpretation); and a method of producing at least one aldehyde and its corresponding carboxylic acid (as in claims 14-29)”. The recited amended claims 1-4, 6-10 and 16-17 (dated 05/14/2026) of co-pending Application No. 17/910,649 (US 2023/0407349 A1) also encompass, “…a genus of polypeptides and the encoding polynucleotides in the claimed method i.e., a polypeptide having alpha-dioxygenase activity, a polypeptide having aldehyde dehydrogenase, a polypeptide having NADH oxidase activity and a polypeptide having aldehyde dehydrogenase activity”; said reference polypeptides having 100% sequence identity to SEQ ID NO: 5 and SEQ ID NO: 9 of the instant invention (see provided sequence alignments), as claimed in claims 14-29 of the instant application and falls entirely within the scope of claims 1-4, 6-10 and 16-17 (dated 05/14/2026) of co-pending Application No. 17/910,649 (US 2023/0407349 A1) and in view of Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention (see provided sequence alignment). Additionally Walter et al., (UniProtKB/TrEMBL Accesion#A0A6M0SDT9, 10/07/2020) disclosing an alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention; said reference provides Teaching, Suggestion and Motivation for adding alpha-dioxygenase having 98.0% sequence identity to SEQ ID NO: 1 of the instant invention in the claimed method of the instant invention. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
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