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 .
Applicants’ amendment to the claims filed on 3/30/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 15-31 are pending.
Claims 19-31 are newly added.
Claims 1-14 are canceled.
Election/Restrictions
Applicant’s election without traverse of Group II, encompassed by pending claims 15-31 in the reply filed on 3/30/2026 is acknowledged.
Claims 15-31 are pending.
Claims 1-14 are canceled.
Priority
Acknowledgement is made of this national stage entry of PCT/EP2022/068916 filed on 7/7/2022, which claims domestic priority to U.S. non-provisional application 18/578,581, filed on 97/7/2022, which claims foreign priority to European Patent Application Number EP21185143.1, filed on 7/12/2021. The certified copy has been filed in the present application on 1/11/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/11/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Rejections - 35 USC § 112
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 23, 25 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.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states 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. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 23 is drawn to the process for the production of ethanol, wherein the protein having transketolase activity comprises or consists of: an amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27; or a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27; or a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 having one or more mutations, substitutions, insertions and/or deletions when compared with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO:15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27. The structure of a process for producing ethanol comprising the remaining amino acids beyond 70% sequence identity to the recited SEQ ID NO’s are a large number of sequences. Furthermore, the structure of a process for producing ethanol comprising a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 having one or more mutations, substitutions, insertions and/or deletions when compared with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO:15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 are a large number of sequences as the recitation ‘having one or more mutations, substitutions, insertions and/or deletions’ encompass a large number of variation thereby also encompasses a large number of sequences.
Claim 25 is drawn to the process for the production of ethanol, wherein the recombinant yeast cell is a recombinant Saccharomyces cerevisiae yeast cell, functionally expressing a heterologous nucleic acid sequence encoding a protein having transketolase activity, wherein: the protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9; or the heterologous nucleic acid sequence comprises or consists of a nucleic acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10. The structure of a process for producing ethanol comprising an amino acid sequence equal to or more than 30% to equal to or less than 80% sequence identity to SEQ ID NO: 9 and a nucleic acid sequence equal to or more than 30% to equal to or less than 80% sequence identity to SEQ ID NO: 10 are a large number of sequences as there are a large number of nucleic acid sequences that encompasses more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10. Furthermore, it is unknown the process for producing ethanol wherein the amino acid sequences that are equal to or more than 30% to equal to or less than 80% sequence identity to SEQ ID NO: 9 as there are a large number of protein sequences that encompasses more than 30% to equal to or less than 80% sequence identity with the protein sequence of SEQ ID NO: 9.
In this case, the specification discloses the following representative protein having transketolase activity for producing ethanol as encompassed by the claims (i.e. the amino acid sequence of SEQ ID NO: 9, 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27). The specification discloses the following representative process for producing ethanol comprising protein having one of more mutations, substitutions, insertions and/or deletions as encompassed by the claims (i.e. the nucleic acid sequence of any such functional homologues has no more than 300, no more than 250, no more than 200, no more than 150, no more than 100, no more than 75, no more than 50, no more than 40, no more than 30, no more than 20, no more than 10 or no more than 5 nucleic acid mutations, substitutions, insertions and/or deletions as compared to such nucleic acid sequences). The specification discloses the following representative process for producing ethanol comprising nuclei acid sequence having transketolase activity as encompassed by the claims (i.e. SEQ ID NO: 10). Other than the above disclosed species, there is no prior art or disclosed teaching as to the large number of processes for producing ethanol comprising sequences that are the remaining amino acids (SEQ ID NO: 9, 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27) and nucleic acids (SEQ ID NO: 10) of the claimed transketolase.
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the disclosure fails to teach which amino acids out of the numerous possibilities encompass transketolase beyond the 70%. The disclosure fails to teach the protein and nucleic acid sequences beyond the 30%-80% sequence identity. Additionally, the disclosure fails to teach which amino acids are mutated, substituted, inserted and deleted out of the numerous possibilities that encompass transketolase.
Accordingly, one of skill in the art would not accept the disclosure of a process for producing ethanol comprising functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27; a process for producing ethanol comprising a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 having one or more mutations, substitutions, insertions and/or deletions; a process for producing ethanol comprising protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9; or the heterologous nucleic acid sequence comprises or consists of a nucleic acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10 as being representative of all transketolase as encompassed by the claims. As such, the specification, taken with the pre-existing knowledge in the art of transketolase, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 112
Claims 23, 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a process for producing ethanol comprising SEQ ID NO: 9, 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 in yeast cells being representative of homologues of transketolase protein and SEQ ID NO: 10 being a representative of homologues of transketolase nucleic acids, it does not reasonably provide enablement for all methods for producing ethanol comprising protein and nucleic acids homologues of transketolase with 70% sequences identity to SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27; it does not provide enablement of all processes for ethanol production comprising amino acid sequence homologues of transketolase having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9; it does not provide enablement for all a process for producing ethanol comprising nucleic acid sequence homologues of transketolase having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10. 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/or use the invention commensurate in scope with these claims.
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
(A)The breadth of the claims
Claim 23 is drawn to the process for producing ethanol, wherein the protein having transketolase activity comprises or consists of: an amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27; or a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27; or a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 having one or more mutations, substitutions, insertions and/or deletions when compared with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO:15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27. The structure of a process for producing ethanol comprising transketolase functional homologue beyond 70% sequence identity to the recited SEQ ID NO’s are a large number of sequences. Furthermore, the structure of a process for producing ethanol comprising functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 having one or more mutations, substitutions, insertions and/or deletions when compared with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO:15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 are a large number of sequences as the recitation ‘having one or more mutations, substitutions, insertions and/or deletions’ encompass a large number of variation thereby also encompass a large number of sequences.
Claim 25 is drawn to the process for producing ethanol, wherein the recombinant yeast cell is a recombinant Saccharomyces cerevisiae yeast cell, functionally expressing a heterologous nucleic acid sequence encoding a protein having transketolase activity, wherein: the protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9; or the heterologous nucleic acid sequence comprises or consists of a nucleic acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10. The structure of a process for producing ethanol comprising an amino acid sequence equal to or more than 30% to equal to or less than 80% sequence identity to SEQ ID NO: 9 and a nucleic acid sequence equal to or more than 30% to equal to or less than 80% sequence identity to SEQ ID NO: 10 are a large number of sequences as it is unknown the nucleic acids the encompass more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10. Furthermore, the structure of a process for producing ethanol comprising amino acid sequences that are equal to or more than 30% to equal to or less than 80% sequence identity to SEQ ID NO: 9 is a large number of sequences.
B) The nature of the invention; C)The state of the prior art; (D) The level of one of ordinary skill; and (E) The level of predictability in the art: As noted above, the scope of the claimed amino acids of the CRISPR nuclease is a large number of sequences. The structure of the claimed transketolase for the production of ethanol are a large number of sequences.
It is well-known in the prior art that the amino acid sequence of a polypeptide determines the polypeptide’s functional properties. The positions within a protein's sequence where modifications can be made with a reasonable expectation of success in obtaining a polypeptide having the desired activity/utility are limited in any protein and the result of such modifications is highly unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g., multiple substitutions. The reference of Singh et al. (Current Protein and Peptide Science, 2017; examiner cited) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes [see p. 7, column 1, top]. The reference of Zhang et al. (Structure, 2018; examiner cited) discloses that a mutation of a residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide [p. 1475, column 1].
It is well-known in the art that even a single amino acid alteration can alter the folding of a polypeptide. See, e.g., MPEP 2144.08.II.A.4.(c), which states, “[i]n the area of biotechnology, an exemplified species may differ from a claimed species by a conservative substitution (“the replacement in a protein of one amino acid by another, chemically similar, amino acid... [which] is generally expected to lead to either no change or only a small change in the properties of the protein.” Dictionary of Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)). The effect of a conservative substitution on protein function depends on the nature of the substitution and its location in the chain. Although at some locations a conservative substitution may be benign, in some proteins only one amino acid is allowed at a given position. For example, the gain or loss of even one methyl group can destabilize the structure if close packing is required in the interior of domains. James Darnell et al., Molecular Cell Biology 51 (2d ed. 1990).”
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of functional homologues of transketolase for producing ethanol comprising (i.e. the amino acid sequence of SEQ ID NO: 9, 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 and the nucleic acid sequence of SEQ ID NO: 10). Other than the above disclosed species, there is no prior-art or disclosed teaching of a process for producing ethanol as to the large number of sequences comprising functional transketolase homologues for the production of ethanol. Other than the above disclosed species, there is no prior-art or disclosed teaching of a process for producing ethanol comprising functional transketolase homologues through genetic modification of genes encoding proteins or post-translational modifications, etc. via any modification technique such as deletion, mutation, etc. for the production of ethanol. Other than these working examples, the specification fails to disclose any other processes for producing ethanol comprising working examples of functional transketolase homologues for production of ethanol.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. 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 claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of 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).
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.
Claims 17-18, 21, 23, 26 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 17 (claim 18 dependent thereof), the phrase " at least partly carried out" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. It is not clear if the items/phrases followed by this phrase are to be considered as claim limitations. Appropriate correction is suggested. See MPEP § 2173.05(d). Appropriate correction is suggested.
Regarding claim 21, the phrase "wherein a native nucleic acid sequence encoding for a protein having transketolase activity is under control of the promoter" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. Based on how the claim is recited, it is unclear if Applicant intends a native nucleic acid sequence encoding for a protein having transketolase activity to be part of the process of independent claim 15 or an additional limitation due to the recitation ‘a native nucleic acid…’ of which indicates an additional nucleic acid apart from the claimed nucleic acid within the independent claim 15, upon which claim 21 depends. It is recommended that Applicant amend the claim language to “further comprising a native nucleic acid sequence encoding for a protein having transketolase activity is under control of the promoter" as said limitation, ‘a native nucleic acid…’ is not further limiting.
Regarding claim 23 the phrase " a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 at least 70% sequence identity with the amino acid sequence of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27; a functional homologue of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27 having one or more mutations, substitutions, insertions and/or deletions," renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear if Applicant is referring to a full-length or a fragment with the recitation ‘a functional homologue thereof.’ Said amino acid sequence can encompass any amino acid sequence fragment comprises SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or SEQ ID NO: 27. See MPEP § 2173.05(d).
Regarding claim 26, the phrase "wherein a native nucleic acid sequence encoding for a protein having transketolase activity has been disrupted or deleted" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. Based on how the claim is recited, it is unclear if Applicant intends a native nucleic acid sequence encoding for a protein having transketolase activity has been disrupted or deleted to be part of the process of independent claim 15 or an additional limitation due to the recitation ‘a native nucleic acid…’ of which indicates an additional nucleic acid apart from the claimed nucleic acid within the independent claim 15, upon which claim 26 ultimately depends. It is recommended that Applicant amend the claim language to “wherein the native nucleic acid sequence encoding for a protein having transketolase activity has been disrupted or deleted."
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 15-18, 20-24, 26-31 is rejected under 35 U.S.C. 103 as being unpatentable over Maris et al (EP-3318624-A2, date published: 9/5/2018, Examiner cited) {herein Maris} as evidenced by Kobayashi et al (2017, J Ind Microbiol Biotechnol, Examiner cited) {herein Kobayashi}, Gerstenschlager et al (1993, Eur. J. Biochem., Examiner cited) {herein Gerstenschlager}, Pretorius et al (1991, Taylor & Francis, Examiner cited) {herein Pretorius} and Klein et al (2017, environmental microbiology, Examiner cited) {herein Klein).
Claims 15-18, 20-24, 26-31 are drawn to a process for the production of ethanol, comprising converting a carbon source using a recombinant yeast cell functionally expressing: a) a heterologous nucleic acid sequence encoding a protein having ribulose-1,5- phosphate carboxylase/oxygenase activity (EC4.1.1.39; Rubisco), a heterologous nucleic acid sequence encoding a protein having phosphoribulokinase activity (EC2.7.1.19; PRK) and one or more nucleic acid sequences encoding for molecular chaperones for the protein having ribulose-1,5-phosphate carboxylase/oxygenase activity; and b) a nucleic acid sequence encoding a protein having transketolase activity (EC 2.2.1.1), wherein the expression of the nucleic acid sequence encoding the protein having transketolase activity is under control of a promoter having an anaerobic/aerobic expression ratio for the transketolase of 2 or more.
With respect to claims 15, 18, 20-22, 24, 26-27, 29, Maris teaches a process for the production of ethanol (para 0007) by recombinant yeast (para 0001), Saccharomyces cerevisiae (para 102) grown in medium comprising glucose (para 0102) as a carbon source (para 0006). Said recombinant yeast cell functionally expresses one or more recombinant, in particular heterologous, nucleic acid sequences encoding a ribulose-1,5-biphosphate carboxylase oxygenase (Rubisco) and a phosphoribulokinase (PRK) (para 0017). The micro-organism also comprises a heterologous nucleic acid sequence encoding a first prokaryotic chaperone for said polypeptide (para 0092). Furthermore, said yeast comprises a heterologous nucleic acid sequence functionally expressing a polypeptide selected from the group consisting of transketolases (para 0092) under anaerobic conditions (Maris claim 14). The heterologous nucleic acid sequence may be substantially modified from its native form in composition and/or genomic locus by deliberate human intervention (para 0046) and is operably linked to a promoter functional in the yeast (para 0036). Said promoter may be substantially modified from its original form (para 0046). As such, it would be obvious to one of ordinary skill in that art that said promoter is synthetic as Maris teaches it is substantially modified, thereby not naturally occurring. Evidentiary reference of Gerstenschlager et al is cited to demonstrate that Saccharomyces cerevisiae natively expressed transketolase gene (abstract). As such, it is the Examiner’s position that said construct would necessarily be comprised of heterologous nucleic acid sequence encoding for the protein having transketolase activity in addition to a native nucleic acid sequence encoding for a protein having transketolase activity, as Maris does not teach said native gene is knocked-out. The method may be carried out under aerobic, oxygen-limited or anaerobic conditions (para 0083). Absent evidence otherwise, it is the Examiner’s position that said promoter has an anaerobic/aerobic expression ratio for the transketolase as Maris teaches the expression of the heterologous nucleic acids in anaerobic/aerobic environments. Maris further teaches the promoter may be inducible, thereby the rate of transcription of the gene would be increased in response to an inducible agent (para 0048). As such, it would be obvious to one of ordinary skill in that art to induce the promoter of the transketolase gene as the over expression of said gene would necessarily result in increased production of ethanol as it is known by those of ordinary skill in the art that transketolase functions in the pentose pathway for the production of ethanol. Supporting the Examiner’s position is the evidentiary reference of Kobayashi et al, which recites the overexpression of transketolase results in increased production of ethanol (abstract). As such, it is the Examiner’s position that the expression ratio of transketolase would necessarily be 2 or more, as recited in the instant application claim 15. Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. The functionality of the enzymes is tested by use of an assay system comprising a recombinant yeast cell comprising an expression vector for the expression of the homologue in yeast with said expression vector comprising a heterologous nucleic acid sequence operably linked to a promoter functional in the yeast (para 0036). The skilled person will be able to derive there from how suitable candidate homologues may be found and, optionally upon codon(pair) optimization, will be able to test the required functionality of such candidate homologues using a suitable assay system as (para 0036). A suitable homologue represents a polypeptide having an amino acid sequence similar to a specific polypeptide of at least 70 %, similarity and having the required enzymatic functionality (para 0036). Said homologue refers to a polypeptide comprising said specific sequence with the proviso that one or more amino acids are substituted, deleted, added, and/or inserted, and which polypeptide has (qualitatively) the same enzymatic functionality for substrate conversion (para 0036). With respect to nucleic acid sequences, the term functional homologue is meant to include nucleic acid sequences which differ from another nucleic acid sequence due to the degeneracy of the genetic code and encode the same polypeptide sequence (para 0036).
With respect to claims 17, 30-31, the evidentiary reference of Pretorius is cited to demonstrate that Saccharomyces cerevisiae natively expresses glucoamylase (abstract), of which is a saccharolytic enzyme. Furthermore, the evidentiary reference of Klein is cited to demonstrate that glycerol dehydrogenase (EC 1.1.1.6), dihydroxyacetone kinase and glycerol transporters are native to Saccharomyces cerevisiae (page 880, column 2, para 2; page 886, column 2, para 1). Maris teaches other suitable enzymes that have not (yet) been classified in a specified class but may be classified as such, are meant to be included. As such, it would be obvious to one of ordinary skill in that art that Saccharomyces cerevisiae taught by Maris would necessarily be comprised of a nucleic acid sequence that expresses glucoamylase (EC 3.2.1.20 or 3.2.1.3), glycerol dehydrogenase (EC 1.1.1.6), dihydroxyacetone kinase (E.C. 2.7.1.28 or E.C.2.7.1.29) and glycerol transporters as Maris teaches glycerol is a major by-product during anaerobic production of ethanol by S. cerevisiae, which is undesired as it reduces overall conversion of sugar to ethanol (para 0010). Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 23, Maris teaches a heterologous nucleic acid sequence encoding a polypeptide from an autotrophic organism of which are transketolases (Maris claim 14). Absent evidence otherwise, it is the Examiner position that Maris teaches a protein having transketolase activity that comprises a functional homologue of SEQ ID NO: 11 having one or more mutations, substitutions, insertions and/or deletions when compared with the amino acid sequence of SEQ ID NO: 11 as recited in the instant application claim 23, as it is the Examiner’s position that said recitation encompasses any transketolase with at least 2 contiguous amino acids that are the same as SEQ ID NO: 11 (appendix B). It is also noted that the recitation ‘having one or more mutations, substitutions, insertions and/or deletions’ is sufficiently broad as one or more mutations, substitutions, insertions and/or deletions encompasses a large number of sequences and variability. As such, since Maris teaches functional transketolases (SEQ ID NO: 31), it would be obvious to one of ordinary skill in that art that said transketolases would also include any of the SEQ ID NO’s recited in the instant application claim 23 having one or more mutations, substitutions, insertions and/or deletions since Maris teaches a protein having transketolase activity (Maris, claim 14), of which the recited SEQ ID NO’s encompass (instant application claim 23).
With respect to claim 28, Maris teaches a process wherein the expression cassette of the specific Rubisco form II chaperones from T. denitrificans cbbQ2 and cbbO2, and chaperones groEL and groES from E. coli were codon optimized. The expression cassettes contained a yeast constitutive
promoters (para 0101).
However, Maris does not teach the process of claim 16, wherein the process is at least partly carried out in a medium comprising glucose in a glucose concentration of 25g/L or more (claim 16).
With respect to claim 16, although the reference of Maris does not explicitly teach the limitations of claim 16 (glucose concentration of 25g/L or more), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the concentration of the glucose depending on the particular application. It would be routine for one to arrive at the glucose concentration for the application they intend on using the medium. Therefore, the above invention would have been prima facie obvious.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Maris er al (EP-3318624-A2, date published: 9/5/2018, Examiner cited) {herein Maris} as applied to claims 15-18, 20-24, 26-31 in view of Bont et al (EP 2663645B1, Date of Publication: 17.12.2014, Examiner cited) {herein Bont} as evidenced by Gerstenschlager et al (1993, Eur. J. Biochem., Examiner cited) {herein Gerstenschlager}, Pretorius et al (1991, Taylor & Francis, Examiner cited) {herein Pretorius} and Klein et al (2017, environmental microbiology, Examiner cited) {herein Klein).
Claim 19 is drawn to the process according to claim 15, wherein the promoter is the promoter of a gene selected from the list consisting of: FET4, ANB1, YHR048W, DAN1, AAC3, TIR2, DIPS, HEM13, YNR014W, YAR028W, FUN 57, COX5B, OYE2, SUR2, FRDS1, PIS1, LAC1, YGR035C, YAL028W, EUG1, HEM14, ISU2, ERG26, YMR252C, SML1, TIR2, TIR4, TIR3, PAU7, PAU5, YLL064C, YGR294W, DAN3, YIL176C, YGL261C, YOL161C, PAU1, PAU6, DAN2, YDR542W, YIR041W, YKL224C, PAU3, YLL025W, YOR394W, YHL046C, YMR325W, YAL068C,YPL282C, PAU2, and PAU4.
The teachings of Maris as applied to claims 15-18, 20-24, 26-31 are set forth in the 103 rejection above.
However, Maris does not teach the process of claim 19, wherein the process according to claim 15, wherein the promoter is the promoter of a gene selected from the list consisting of: FET4, ANB1, YHR048W, DAN1, AAC3, TIR2, DIPS, HEM13, YNR014W, YAR028W, FUN 57, COX5B, OYE2, SUR2, FRDS1, PIS1, LAC1, YGR035C, YAL028W, EUG1, HEM14, ISU2, ERG26, YMR252C, SML1, TIR2, TIR4, TIR3, PAU7, PAU5, YLL064C, YGR294W, DAN3, YIL176C, YGL261C, YOL161C, PAU1, PAU6, DAN2, YDR542W, YIR041W, YKL224C, PAU3, YLL025W, YOR394W, YHL046C, YMR325W, YAL068C,YPL282C, PAU2, and PAU4 (claim 19).
With respect to claim 19, Bont teaches a process wherein the promoter ANB1 in S. cerevisiae controls the expression of enzymes such as transketolase (para 0040; 0089) for the production of ethanol (para 0001).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to apply the teachings of Maris et al. of a process for the production of ethanol (para 0007) by recombinant yeast (para 0001) by using a carbon source (para 0006) or combine the teachings of Bont because Bont teaches a process wherein ANB1 in S. cerevisiae controls the expression of enzymes such as transketolase (para 0040; 0089) for the production of ethanol (para 0001).
One of ordinary skill in the art would be motivated to either use the teachings of Maris et al. by itself or combine the teachings of Maris and Bont because Bont provides the motivation for Maris to try using the ANB1 promoter for the expression of transketolase, as Bont teaches ANB1 is insensitive to catabolite (glucose) repression and active under anaerobic conditions (para 0040). One of ordinary skill in the art knowing the benefit of efficient ethanol production based on the teachings of Maris and Bont would have a reasonable expectation of success to try using ANB1 as the promoter within S. cerevisiae for the expression of transketolase as Bont teaches ANB1 is insensitive to catabolite (glucose) repression and active under anaerobic conditions and do not require xylose or arabinose for induction (para 0040), thereby making it a more efficient and effective promoter for the expression of transketolase.
One of skill in the art would have a reasonable expectation of success to make and use the claimed transketolase gene with a ANB1 promoter for the production of ethanol because Maris provides the basic construct and its uses and methods of making it. Reference of Bont provides the teachings for making a transketolase construct under the ANB1 promoter (para 0001, 0040, 0089). Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Maris et al (EP-3318624-A2, date published: 9/5/2018, Examiner cited) {herein Maris} as applied to claims 15-18, 20-24, 26-31 in view of Luo et al (WO 2018112638 A1, Date Published: 28 June 2018, Examiner cited) {herein Luo} as evidenced by Gerstenschlager et al (1993, Eur. J. Biochem., Examiner cited) {herein Gerstenschlager}, Pretorius et al (1991, Taylor & Francis, Examiner cited) {herein Pretorius} and Klein et al (2017, environmental microbiology, Examiner cited) {herein Klein).
Claim 25 is drawn to the process according to claim 22, wherein the recombinant yeast cell is a recombinant Saccharomyces cerevisiae yeast cell, functionally expressing a heterologous nucleic acid sequence encoding a protein having transketolase activity, wherein:- the protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9; or - the heterologous nucleic acid sequence comprises or consists of a nucleic acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10.
The teachings of Maris as applied to claims 15-18, 20-24, 26-31 are set forth in the 103 rejection above.
However, Maris does not teach the process of claim 25, wherein the recombinant yeast cell is a recombinant Saccharomyces cerevisiae yeast cell, functionally expressing a heterologous nucleic acid sequence encoding a protein having transketolase activity, wherein: the protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9; or - the heterologous nucleic acid sequence comprises or consists of a nucleic acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the nucleic acid sequence of SEQ ID NO: 10 (claim 25).
With respect to claim 25, Luo teaches a recombinant Saccharomyces cerevisiae yeast cell, functionally expressing a heterologous nucleic acid sequence encoding a protein having transketolase (Tkl1p) activity, wherein: the protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9 for production of ethanol (table 3, abstract, para 009, 0010, 00108, page 31, appendix A). Furthermore, Luo teaches the enzyme or protein can be fragments of an enzyme or protein of the xylose metabolic pathway such as Metschnikowia Tkl1p (transketolase) (para 00113).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to apply the teachings of Maris et al. of a process for the production of ethanol (para 0007) by recombinant yeast (para 0001) using a carbon source (para 0006) or combine the teachings of Luo because Luo teaches a recombinant Saccharomyces cerevisiae yeast cell, functionally expressing a heterologous nucleic acid sequence encoding a protein having transketolase (Tkl1p) activity, wherein: the protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9 for production of ethanol (table 3, abstract, para 009, 0010, 00108, page 31, appendix A).
One of ordinary skill in the art would be motivated to either use the teachings of Maris et al. by itself or combine the teachings of Luo because Luo provides the motivation for Maris to substitute the transketolase gene of the invention for Tkl1p, taught by Luo, as Luo teaches the nucleic acid encoding Metschnikowia Tkl 1p is codon optimized for expression in S. cerevisiae (para 00124). MPEP 2143.I.B states “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art.” One of ordinary skill in the art knowing the benefit of transketolase for the production of ethanol based on the teachings Maris and Luo would have a reasonable expectation of success to substitute the transketolase taught by Maris with the transketolase taught by Luo, Tkl1p, as it is known by those of ordinary skill in the art that codon optimization enhances protein production by replacing rare codons with frequently used ones, matching the host organism's bias to increase translational efficiency. Thereby said Tkl1p would boost protein yield, improve stability and minimize the misfolding of transketolase within Saccharomyces cerevisiae during ethanol production.
One of skill in the art would have a reasonable expectation of success to make and use the claimed transketolase gene with a ANB1 promoter for the production of ethanol because Maris provides the basic construct and its uses and methods of making it. Reference of Luo provides the teaching of a recombinant Saccharomyces cerevisiae yeast cell, functionally expressing a heterologous nucleic acid sequence encoding a protein having transketolase (Tkl1p) activity, wherein: the protein having transketolase activity comprises or consists of an amino acid sequence having in the range of equal to or more than 30% to equal to or less than 80% sequence identity with the amino acid sequence of SEQ ID NO: 9 for production of ethanol (table 3, abstract, para 009, 0010, 00108, page 31, appendix A). Therefore there would be a reasonable expectation of success to arrive at the above invention. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
Status of Claims
Claims 15-31 are pending.
Claims 1-14 are canceled.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 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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/ERICA NICOLE JONES-FOSTER/Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
Appendix A
Instant Application SEQ ID NO: 11 vs Luo SEQ ID NO: 31
Query Match 71.8%; Score 2530; Length 677;
Best Local Similarity 69.9%;
Matches 474; Conservative 91; Mismatches 109; Indels 4; Gaps 4;
Qy 5 TDIDKLAVSTIRILAVDTVSKANSGHPGAPLGMAPAAHVLWSQMRMNPTNPDWINRDRFV 64
:|||:||:||||:|||| |:||||||||||||:||||| :| :|: || ||||:||||||
Db 2 SDIDQLAISTIRLLAVDAVAKANSGHPGAPLGLAPAAHAVWKEMKFNPKNPDWVNRDRFV 61
Qy 65 LSNGHAVALLYSMLHLTGYDLSIEDLKQFRQLGSRTPGHPE-FELPGVEVTTGPLGQGIS 123
|||||| ||||:|||| |:|:|::|||||||| |:|||||| ||:|| ||||||||||||
Db 62 LSNGHACALLYAMLHLYGFDMSLDDLKQFRQLNSKTPGHPEKFEIPGAEVTTGPLGQGIS 121
Qy 124 NAVGMAMAQANLAATYNKPGFTLSDNYTYVFLGDGCLQEGISSEASSLAGHLKLGNLIAI 183
||||:|:|| |||:|| | :||:||| ||||||| ||::||||||||||:| ||||
Db 122 NAVGLAIA QKQFAATFNKDDFAISDSYTYAFLGDGCLMEGVASEASSLAGHLQLNNLIAF 181
Qy 184 YDDNKITIDGATSISFDEDVAKRYEAYGWEVLYVENGNEDLAGIAKAIA QAKLSKDKPTL 243
:|||||:|||:| ::| ||| ||||||||: | :| |: || |:|:|| || || ||||
Db 182 WDDNKISIDGSTEVAFTEDVLKRYEAYGWDTLTIEKGDTDLEGVAQAIKTAKASK-KPTL 240
Qy 244 IKMTTTIGYGSLHAGSHSVHGAPLKADDVKQLKSKFGFNPDKSFVVPQEVYDHYQKTILK 303
|::|| |||||| |:| ||||||| ||:|||| ||||:| |||||||||||:| |::|
Db 241 IRLTTIIGYGSLQQGTHGVHGAPLKPDDIKQLKEKFGFDPTKSFVVPQEVYDYY-GTLVK 299
Qy 304 PGVEANNKWNKLFSEYQKKFPELGAELARRLSGQLPANWESKLPTYTAKDSAVATRKLSE 363
| ::||| | :|||| || ||||| |:|| :| |||||| | :|||||||
Db 300 KNQELESEWNKTVESYIQKFPEEGAVLARRLKGELPEDWAKCLPTYTADDKPLATRKLSE 359
Qy 364 TVLEDVYNQLPELIGGSADLTPSNLTRWKEALDFQPPSSGSGNYSGRYIRYGIREHAMGA 423
| : : :||||||||||| ||||| : :||||| :| |||:|||||||:||| |||
Db 360 MALIKILDVVPELIGGSADLTGSNLTRAPDMVDFQPPQTGLGNYAGRYIRYGVREHGMGA 419
Qy 424 IMNGISAFGANYKPYGGTFLNFVSYAAGAVRLSALSGHPVIWVATHDSIGVGEDGPTHQP 483
|||||: ||| :: |||||||||||||||||||||| ||||||||||||:|||||||||
Db 420 IMNGIAGFGAGFRNYGGTFLNFVSYAAGAVRLSALSHLPVIWVATHDSIGLGEDGPTHQP 479
Qy 484 IETLAHFRSLPNIQVWRPADGNEVSAAYKNSLESKHTPSIIALSRQNLPQLEGSSIESAS 543
||||||||: ||| |||||||||||||||:::|| || |:||:||||||| |||:| ||
Db 480 IETLAHFRATPNISVWRPADGNEVSAAYKSAIESTSTPHILALTRQNLPQLAGSSVEKAS 539
Qy 544 KGGY-VLQDVANPDIILVATGSEVSLSVEAAKTLAAKNIKARVVSLPDFFTFDKQPLEYR 602
||| | | | :|:||:||||::|::||| | : ||| |||| || |||||||:||
Db 540 TGGYTVYQTTDKPAVIIVASGSEVAISIDAAKKLEGEGIKANVVSLVDFHTFDKQPLDYR 599
Qy 603 LSVLPDNVPIMSVEVLATTCWGKYAHQSFGIDRFGASGKAPEVFKFFGFTPEGVAERAQK 662
|||||| ||||||||::: | ||:|: ||::|||||||| :::||| |||||||:|| |
Db 600 LSVLPDGVPIMSVEVMSSFGWSKYSHEQFGLNRFGASGKAEDLYKFFDFTPEGVADRAAK 659
Qy 663 TIAFYKGDKLISPLKKAF 680
|: |||| |:||| :||
Db 660 TVQFYKGKDLLSPLNRAF 677
Appendix B
Instant Application SEQ ID NO: 11 vs Luo SEQ ID NO: 31
Query Match 71.8%; Score 2530; DB 1; Length 677;
Best Local Similarity 69.9%;
Matches 474; Conservative 91; Mismatches 109; Indels 4; Gaps 4;
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641
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Prosecution Insights