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. Applicant’s amendment to the claims filed on 08/13/2026 in response to the Non-Final Rejection mailed on 04/14/2025 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. New claims 11-18 are added.
4. Claims 1 and 6-18 are pending.
5. Claims 8-10 stand withdrawn pursuant to 37 CFR 1.142(b).
6. Applicant’s remarks filed on 08/13/2026 in response to the Non-Final Rejection mailed on 04/14/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Claim Rejections - 35 USC § 112(b)
7. The rejection of claims 1 and 6-7 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of applicants’ amendment to the claims to recite “comprising the amino acid sequence of any….”.
8. Claims 13-18 are newly 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. This new grounds of rejection is necessitated by applicants’ amendment to the claims to add new claims 14-18.
Claims 13-18 depend upon claim 1 which recites “non-naturally occurring additive”; however, the terms starch, dextrin, maltose, phosphates, citrates, acetates, ascorbic acid, etc. all are naturally occurring compounds. It is unclear how the additives of claim 13-18 are non-naturally occurring. It is suggested that applicants’ clarify the meaning of the claims.
Claim Rejections - 35 USC § 112(a)
8. The written description rejection of claims 1 and 6-7 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and to incorporate new claims 11-18.
Claims 1, 6-7 and 11-18 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.
As amended, claims 1, 6-7, and 11-18 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 comprising 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; (b) a polypeptide comprising 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 comprising an amino acid sequence having sequence identity of 85% 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; cited on PTO-892 mailed on 04/14/2026) 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; cited on PTO-892 mailed on 04/14/2026) 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; cited on PTO-892 mailed on 04/14/2026) 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; cited on PTO-892 mailed on 04/14/2026) 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).
RESPONSE TO REMARKS: Beginning on p. 5 of applicants’ remarks, applicants in summary contend that the claims have been amended and the present specification describes the identification of positions at which it is preferable not to introduce mutations and describes conservative substitutions.
These arguments are found to be not persuasive because MPEP 2163.II.A.3.(a).ii states "when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the genus]." See Enzo Biochem, S2S F.Sd at 966, 63 USPQ2d at 1615; Noelle V. Ledermon, 355 F.3d 1343,1350, 69 USPQ2d 1508,1514 (Fed. Cir. 2004) (Fed. Cir. 2004)". In the instant case, while applicants point to a generic disclosure of substitutions, deletions and insertions, it fails to show species of polypeptides having these modifications. While one skilled in the art may be able to make predictions about the effect of modifications on the polypeptide, this at most describes a research plan rather than showing the inventors were in fact in possession of the full scope of the invention as claimed. The examiner’s position is further supported by the Federal Circuit decision in Novozymes v. Dupont, July 2013. The court found that the claims to a narrowly recited specific alpha-amylase at a single amino acid position was not adequately described or supported by the written description as the application provided only a generalized guidance listing several variables that might, in some combination, lead to a useful result.
9. The scope of enablement rejection of claims 1 and 6-7 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and to incorporate new claims 11-18.
Claims 1, 6-7 and 11-18 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: As amended, claims 1, 6-7, and 11-18 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 comprising 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; (b) a polypeptide comprising 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 comprising an amino acid sequence having sequence identity of 85% 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. 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 15% 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; cited on PTO-892 mailed on 04/14/2026) 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; cited on PTO-892 mailed on 04/14/2026) 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; cited on PTO-892 mailed on 04/14/2026) 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; cited on PTO-892 mailed on 04/14/2026) 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).
RESPONSE TO REMARKS: Beginning on p. 6 of applicants remarks, applicants contend that in view of the amendments and as discussed in relation to the written description, the claims are in compliance with the enablement requirement.
This argument is found to be not persuasive because while applicants point to a generic disclosure of substitutions, deletions and insertions, it fails to show by working examples of polypeptides having these modifications. While the application does disclose that substitutions, deletions and insertions can be made to the claimed sequence, such modifications are only among a list of the many possible combinations of modifications that can be made to the polypeptide. The amount of experimentation needed to make and test each possible substitution, deletion and insertion as encompassed by the claims would be unnecessarily undue.
10. Claims 1, 6-7, and 11-18 are newly 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. This new grounds of rejection is necessitated by applicants’ amendment to the claims to recite “non-naturally occurring additive” in claim 1 and to add new claims 11-18.
MPEP § 2163.11.A.3.(b) states, "when filing an amendment an applicant shouldshow support in the original disclosure for new or amended claims" and "[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description". According to MPEP § 2163.I.B, "While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure" and "The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as nowclaimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117".
In the instant case, claim 1 (claims 6-7 and 11-18 dependent therefrom) recite the limitation “a non-naturally occurring additive”. The examiner has reviewed the specification and found no disclosure to support the full breadth of the term “non-naturally occurring”. Accordingly, the recited limitation constitutes new matter.
Claim Rejections - 35 USC § 101
11. The rejection of claims 1 and 6-7 under 35 U.S.C. 101 because the claimed invention is directed to a nature base product without significantly more is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims and to incorporate new claims 11-18.
Claims 1, 6-7, and 11-18 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 comprising the 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 comprising 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 85% 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 it 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. 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. Furthermore, the recitation of “non-naturally occurring additive” does not transform the enzyme into something that is markedly different as “non-naturally occurring additives” are recited in the dependent claims as encompassing substances that are also naturally occurring, and there is no evidence of record to suggest that these additives are markedly different from their natural counterpart. Nor is there any evidence of record that these additives when in combination with the deamidase transform the enzyme into something that is markedly different from the naturally occurring enzyme. As such the claims are not patent eligible under 35 U.S.C. 101.
RESPONSE TO REMARKS: Beginning on p. 6 of applicants’ remarks, applicants in summary contend that the claim has been amended to recite “non-naturally occurring additive”.
This argument is found to be not persuasive in view of the modified rejection set forth above.
Claim Rejections - 35 USC § 102
12. The rejection of claims 1 and 6-7 under 35 U.S.C. 102(a)(1) as being anticipated by Yamaguchi et al. (US Patent 7462477 B2, 12/09/2008; cited on PTO-892 mailed on 04/14/2026) is withdrawn in view of applicants’ amendment to the claims. Yamaguchi et al. fails to teach and suggest the protein deamidating enzyme as claimed.
Conclusion
13. Status of the claims:
Claims 1 and 6-18 are pending.
Claims 8-10 stand withdrawn pursuant to 37 CFR 1.142(b).
Claims 1, 6-7 and 11-18 are rejected.
No claims are in condition for an allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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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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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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