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 .
Applicant’s cancellation of claims 2,10 and amendment of claim 1, in the paper of 1/14/2026, is acknowledged. Claims 1, 3-9, 11, 13-21 are still at issue and are present for examination.
Election/Restrictions
Applicant's election with traverse of the invention of Group 1, claims 1-9, 11, 15-21, to a DNase variant, in the paper of 1/14/2026, is acknowledged. Applicant's election with traverse of the following species:
Species Group 1: Y182H;
Species Group 2: S68;
Species Group 3: P in position 22, L in position 27, P in position 39, G in position 42, D in position 11;
Species Group 5: W57S;
in the paper of 1/14/2026, is acknowledged.
It is noted that applicants did not elect a species form Species groups 4, 6 and 7.
Claims 13 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Applicants filing of information disclosure statements on 8/23/2023 and 12/3/2025 are acknowledged and have been considered.
Specification
The disclosure is objected to because of the following informalities:
The use of the terms: Triton (page 63, bottom of page), Tween (page 62, line10 and line 14 ) which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1, 3-9, 11, 15-17, 19-21 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.
Newly amended claim 1 (claims 3-9, 11, 15-17, 19-21 dependent on) is indefinite in the newly added recitation “S130DI” as it is unclear and confusing as to what “S130DI” is intended to mean. Does it mean the substitution of position S130 with a “D” or “I”? Applicants specification does not support “S130DI” and thus it is unclear as to applicants intended meaning?
Appropriate correction and/or comment is required.
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.
Claim(s) 1, 3-9, 11, 15-16, 19-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim(s) 1, 3-9, 11, 15-16, 19-21 are directed to all possible DNase variant which compared to the polypeptide of SEQ ID NO: 1 comprises one or more mutations selected from the group consisting of Q14Y, Q14F; N16A; L27W; P39Q; K52M ; T65Y; S66F, S66L, S66A, S66G, or S66H; S68K, S68Q, or S68M; Y77H; T79H; S82DI; S98N; G99N; S106P; A125R; S130DI; P144W;G145*; C148D; G149D; W154T, W154F, or W154V; L181P, L181N, or L181 K; and Y182H, Y182P, or Y182*; wherein the variant has a mere 60% sequence identity to SEQ ID NO: 1 and has DNase activity. Claim(s) 5 and 15-16 are directed to the above DNase variants having a mere 70%, 80% and 85% sequence identity to SEQ ID NO:1. The specification, however, only provides the representative species of that DNase variants comprising the amino acid sequence of SEQ ID NO: 1, encompassed by these claims. There is no disclosure of any particular structure to function/activity relationship in the disclosed species. The specification also fails to describe additional representative species of these DNase variants by any identifying structural characteristics or properties, for which no predictability of structure is apparent.
Regarding the level of skill and knowledge in the art of amino acid mutation, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) 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). Also, the unpredictability associated with amino acid mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
Given this lack of additional representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim(s) 1, 3-9, 11, 15-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention on the basis that the newly added substitution “S130DI” is not supported by applicants specification at the time of filing and is thus considered new matter.
Claim(s) 1, 3-9, 11, 15-16, 19-21 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for that DNase variant of SEQ ID NO: 1 which comprises one or more mutations selected from the group consisting of Q14Y, Q14F; does not reasonably provide enablement for all possible DNase variants which compared to the polypeptide of SEQ ID NO: 1 comprises one or more mutations selected from the group consisting of Q14Y, Q14F;. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claim(s) 1, 3-9, 11, 15-16, 19-21are so broad as to encompass all possible DNase variants which compared to the polypeptide of SEQ ID NO: 1 comprises one or more mutations selected from the group consisting of Q14Y, Q14F;guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the proteins' structure relates to its function. However, in this case the disclosure is limited to that DNase variant of SEQ ID NO: 1 which comprises one or more mutations selected from the group consisting of Q14Y, Q14F;
While recombinant and mutagenesis techniques are known, it is not routine in the art to screen for multiple substitutions or multiple modifications, as encompassed by the instant claims, and the positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is 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 specification does not support the broad scope of the claims which encompass any possible DNase variants which compared to the polypeptide of SEQ ID NO: 1 comprises one or more mutations selected from the group consisting of Q14Y, Q14F;and Y182H, Y182P, or Y182*; wherein the variant has a mere 60% sequence identity to SEQ ID NO: 1 and has DNase activity, because the specification does not establish: (A) regions of the DNases which may be modified effecting the DNase activity; (B) the general tolerance of enzymes of DNases to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue of a DNase enzyme with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. Because of this lack of guidance, the extended experimentation that would be required to determine which substitutions would be acceptable to retain the required lipase activities and the fact that the relationship between the sequence of a peptide and its tertiary structure (i.e. its activity) are not well understood and are not predictable (e.g., see Ngo et al. in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz et al. (ed.), Birkhauser, Boston, MA, pp. 433 and 492-495; Franceus et al., J. Ind. Microbiol. Biotechnol. Vol 44, pp 687-695, 2017), it would require undue experimentation for one skilled in the art to arrive at the majority of those DNase variants of the claimed genus.
Thus, applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including any DNase variant which compared to the polypeptide of SEQ ID NO: 1 comprises one or more mutations selected from the group consisting of Q14Y, Q14F;L181N, or L181 K; and Y182H, Y182P, or Y182*; wherein the variant has a mere 60% sequence identity to SEQ ID NO: 1 and has DNase activity. 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 those DNase variants 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 § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 5, 9, 11, 15, 16, 17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beier et al. (WO 2018/011276).
Beier et al. (WO 2018/011276) teach Bacillus CIBI DNase variants and uses thereof. Beier et al. (WO 2018/011276) teach detergent compositions comprising DNase variants exhibiting alterations relative to the parent DNase in one or more properties including wash performance, detergent stability and/or storage stability. Beier et al. (WO 2018/011276) teach a DNase variant comprising the amino acid sequence of SEQ ID NO:1 (90.1% sequence identity to instant SEQ ID NO:1). Beier et al. (WO 2018/011276) teach the above DNase variant of SEQ ID NO:1 comprising a S68K substitution (see page 4, middle of page and supporting text).
Claim(s) 1, 5, 9, 11, 15, 16, 17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Beier et al. (WO 2018/011276).
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
3/2/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652