DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicants’ amendment to the claims filed on 03/19/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 2-5 are cancelled.
4. Claims 1 and 6-10 are pending.
Election/Restrictions
5. Applicant’s election without traverse of Group I, claims 1 and 6-7 and the species, SEQ ID NO: 2 in the reply filed on 03/19/2026 is acknowledged.
6. Claims 8-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/19/2026.
Claims 1 and 6-7 are pending and will be examined to the extent that they read on the elected species, SEQ ID NO: 2.
Priority
7. Acknowledgement is made of applicant’s claim for foreign priority under 35 U.S.C. 119(a)-(d) to Japan Patent Application JP2021-016088, filing date 02/03/2021. The certified copy has been filed in the present application, filed on 08/02/2023.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d), a certified English translation of the foreign application must be submitted. See 37 CFR 41.154(b).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
8. The IDSs filed on 08/02/2023, 12/30/2024, and 02/13/2026 have been considered by the examiner and copies of the Form PTO/SB/08 are attached to the office action.
Claim Rejections - 35 USC § 112(b)
9. 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.
10. Claims 1 and 6-7 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.
Claims 1 and 6-7 are drawn in relevant part to a protein deamidating enzyme comprising a polypeptide as defined in any of (a) to (c) below: (a) a polypeptide including an amino acid sequence of any of SEQ ID NO: 2, or an amino acid sequence at positions 381-564 of SEQ ID NO: 2. The recitation of “an amino acid sequence of any of SEQ ID NO: 2…” is indefinite because the use of the grammatically indefinite article “an” as it relates to the sequence renders the metes and bounds of the claim undetermined. It is unclear whether the polypeptide “including an amino acid sequence” is intended to be the full length sequence of SEQ ID NO: 2 or fragments of said sequence. In the interest of compact prosecution, the claims will be interpreted as encompassing fragments of SEQ ID NO: 2 such that said sequence need only to share two contiguous amino acids with the claimed sequence. It is suggested that applicants clarify the meaning of the claims.
Claim Rejections - 35 USC § 112(a)
11. 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.
A. Written Description
12. Claims 1 and 6-7 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.
Claims 1 and 6-7 are drawn in relevant part to a protein deamidating enzyme comprising a polypeptide as defined in any of (a) to (c) below: (a) a polypeptide including an amino acid sequence of any of SEQ ID NO: 2, or an amino acid sequence at positions 381-564 of SEQ ID NO: 2; (b) a polypeptide including an amino acid sequence providing by substituting, adding, inserting, or deleting one or several amino acids to or from the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381 to 564 of SEQ ID NO: 2, the polypeptide having catalytic activity for a reaction of deamidating a glutamine residue of a protein; (c) a polypeptide including an amino acid sequence having sequence identity of 70% or more with the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381-564 of SEQ ID NO: 2.
In this case, the specification discloses an actual reduction to practice of the following representative species of the genus of “protein deamidating enzyme” as encompassed by the claims (i.e. a protein deamidating enzyme comprising the amino acid sequence of SEQ NOs: 1-11 and having glutaminase activity). Other than the above disclosed species there is no other drawings or structural formulas of the infinite polypeptides of any function as encompassed by the claims.
Applicants’ specification discloses in paragraph 0003 that protein-glutaminases are extremely peculiar enzymes that despite their high utility and interest, have not been newly discovered over a long period of time.
Huang et al. (CN107325977A, 11/07/2017; machine translation attached) discloses that glutaminases, proteases, and peptidoglutaminase can all be used for the deamidation of proteins; however, they all have certain drawbacks: excessive use of glutamine transferase can cause protein aggregation, proteases can hydrolyze proteins as a whole, have poor substrate specificity, and are prone to producing a bitter tase [see paragraph 0005]. Huang et al. further teach that due to the scarcity of glutaminase producing strains, research on the enzyme has been limited [see paragraph 0006].
Yamaguchi et al. (US Patent 7462477, 2008; examiner cited) discloses a glutaminase from the genus of Chryseobacterium that can act on glutamine in a protein [see Column 5]; however, Yamaguchi et al. teach that discovery of glutaminases and asparaginases that can act on a protein are limited [see columns 1-2].
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].
To this end, there is no prior art or disclosed teaching regarding the structure and additions, insertions, deletions, and substitutions to a protein deamidating enzyme as recited in the claims, and there is no disclosed or art recognized correlation between any structure other than the amino acid sequence of SEQ ID NOs: 1-11. Given what is known in the art about the likely outcome of substitutions on structure, conservation of structure is not necessarily a surrogate for conservation of function. In this case, there is no disclosed correlation between structure and function. Accordingly, one of skill in the art would not accept the disclosure of a protein deamidating enzyme comprising the amino acid sequence of SEQ ID NOs: 1-11 as being representative of all protein deamidating enzymes as encompassed by the claims. . As such, the specification, taken with the pre-existing knowledge in the art of amino acid substitution and enzymology, fails to satisfy the written description requirement of 35 U.S.C. 112(a).
B. Scope of Enablement
13. Claims 1 and 6-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling for a protein deamidating enzyme comprising the amino acid sequence of SEQ NOs: 1-11 and having glutaminase activity does ont reasonably provide enablement for all protein deamidating enzymes as encompassed by the claims. 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: Claims 1 and 6-7 are drawn in relevant part to a protein deamidating enzyme comprising a polypeptide as defined in any of (a) to (c) below: (a) a polypeptide including an amino acid sequence of any of SEQ ID NO: 2, or an amino acid sequence at positions 381-564 of SEQ ID NO: 2; (b) a polypeptide including an amino acid sequence providing by substituting, adding, inserting, or deleting one or several amino acids to or from the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381 to 564 of SEQ ID NO: 2, the polypeptide having catalytic activity for a reaction of deamidating a glutamine residue of a protein; (c) a polypeptide including an amino acid sequence having sequence identity of 70% or more with the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381-564 of SEQ ID NO: 2. In view of the indefiniteness of the of the grammatically indefinite article “an” as it relates to the sequence, the structure and function of the claimed polypeptide is unlimited. The structure of the polypeptide having a substitution, addition, deletion, or insertion that results in a polypeptide having catalytic activity for a reaction of deamidating a glutamine residue of protein is unlimited. The structure of the polypeptide that is capable of accepting up to 30% sequence variation and still result in a protein deamidating enzyme is unlimited.
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 structure and function of the claimed protein deamidating enzyme is unlimited.
Applicants’ specification discloses in paragraph 0003 that protein-glutaminases are extremely peculiar enzymes that despite their high utility and interest, have not been newly discovered over a long period of time.
Huang et al. (CN107325977A, 11/07/2017; machine translation attached) discloses that glutaminases, proteases, and peptidoglutaminase can all be used for the deamidation of proteins; however, they all have certain drawbacks: excessive use of glutamine transferase can cause protein aggregation, proteases can hydrolyze proteins as a whole, have poor substrate specificity, and are prone to producing a bitter tase [see paragraph 0005]. Huang et al. further teach that due to the scarcity of glutaminase producing strains, research on the enzyme has been limited [see paragraph 0006].
Yamaguchi et al. (US Patent 7462477, 2008; examiner cited) discloses a glutaminase from the genus of Chryseobacterium that can act on glutamine in a protein [see Column 5]; however, Yamaguchi et al. teach that discovery of glutaminases and asparaginases that can act on a protein are limited [see columns 1-2].
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.
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).”
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].
(F) The amount of direction provided by the inventor and (G) The existence of working examples: The specification discloses the following working examples of protein deamidating enzyme, i.e. a protein deamidating enzyme comprising the amino acid sequence of SEQ NOs: 1-11 and having glutaminase activity. Other than these working examples, the specification fails to disclose any other working examples of protein deamidating enzymes. Moreover, the specification fails to provide guidance regarding what additional modifications to said protein deamidating enzyme that results in the desired activity.
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).
Claim Rejections - 35 USC § 101
14. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
15. Claims 1 and 6-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature base product without significantly more. The claim(s) recite(s) in relevant part to a protein deamidating enzyme comprising a polypeptide as defined in any of (a) to (c) below: (a) a polypeptide including an amino acid sequence of any of SEQ ID NO: 2, or an amino acid sequence at positions 381-564 of SEQ ID NO: 2; (b) a polypeptide including an amino acid sequence providing by substituting, adding, inserting, or deleting one or several amino acids to or from the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381 to 564 of SEQ ID NO: 2, the polypeptide having catalytic activity for a reaction of deamidating a glutamine residue of a protein; (c) a polypeptide including an amino acid sequence having sequence identity of 70% or more with the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381-564 of SEQ ID NO: 2. This judicial exception is not integrated into a practical application because given the breadth of the claim encompassing fragments of any protein deamidating enzymes, it is sufficiently broad to encompass any protein deamidating enzyme such the glutaminase from the genus of Chryseobacterium that can act on glutamine in a protein as disclosed by Yamaguchi et al. (US Patent 7462477, 2008; examiner cited). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional limitations only serve to limit the function of the enzyme, which is a feature inherent to the enzyme itself. Even assuming arguendo that the claims were limited to the full length sequence of SEQ ID NO: 2, this interpretation is not sufficient to transform the enzyme into something that is markedly different from its natural counterpart as the specification in Table 1 discloses that the full length SEQ ID NO: 2 is from Halobacteriovoraceae bacterium, and provides no evidence that this is not a natural deamidase enzyme. As such the claims are not patent eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 102
16. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
17. Claim(s) 1 and 6-7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yamaguchi et al. (US Patent 7462477 B2, 12/09/2008; examiner cited).
18. Claims 1 and 6-7 are drawn in relevant part to a protein deamidating enzyme comprising a polypeptide as defined in any of (a) to (c) below: (a) a polypeptide including an amino acid sequence of any of SEQ ID NO: 2, or an amino acid sequence at positions 381-564 of SEQ ID NO: 2; (b) a polypeptide including an amino acid sequence providing by substituting, adding, inserting, or deleting one or several amino acids to or from the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381 to 564 of SEQ ID NO: 2, the polypeptide having catalytic activity for a reaction of deamidating a glutamine residue of a protein; (c) a polypeptide including an amino acid sequence having sequence identity of 70% or more with the amino acid sequence of any of SEQ ID NO: 2 or the amino acid sequence at positions 381-564 of SEQ ID NO: 2.
19. With respect to claim 1, Yamaguchi et al. teach a protein deamidating enzyme from Chrysobacterium having catalytic activity for deamidating a glutamine residue of a protein [see Abstract; columns 5 and 7]. In view of the indefiniteness of the phrase (a) a polypeptide including an amino acid sequence of any of SEQ ID NO: 2, or an amino acid sequence at positions 381-564 of SEQ ID NO: 2, the deamidating enzyme of Yamaguchi is interpreted as reading on part (a) of claim 1. Furthermore, given the breadth of an amino acid sequence provided by substituting, adding, inserting, or deleting one or several amino acids to or from the amino acid sequence of SEQ ID NO: 2, the teachings of Yamaguchi read on part (b) of claim 1.
With respect to claim 6, Yamaguchi et al. teach an enzyme preparation protein comprising the deamidating enzyme from Chrysobacterium having catalytic activity for deamidating a glutamine residue of a protein [see Abstract; columns 5, 7, and 23].
With respect to claim 7, the recitation of “which is a modifier for a food or drink or a material for a food or drink, an industrial material, or a pharmaceutical material containing a protein”, this language does not require steps to be performed or limit the claim to a particular structure and does not limit the scope of the claim. See MPEP 2106.C and 2111.04. Instead, the “wherein” clause merely recites a correlation between the deamidating enzyme and its usefulness as a modifier for a food or drink or a material for a food or drink, an industrial material, or a pharmaceutical material containing a protein. Nevertheless, Yamaguchi et al. teach the use of the enzyme preparation as a modifier for a food or a drink [see Column 5].
Conclusion
20. Status of the claims:
Claims 1 and 6-10 are pending.
Claims 8-10 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 1 and 6-7 are rejected.
No claims are in condition for an allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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