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 .
Election/Restrictions
Applicant’s election without traverse of group I, claims 1, 4-7, 14, 18, and 19 in the reply filed on 12/17/25 is acknowledged.
Applicant’s election without traverse of the species of SEQ ID 4, position 30 of SEQ ID 4 and LC-MS in the reply filed on 12/17/25 is acknowledged.
Claim 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/17/25.
Claims 1, 4-6, 14, 18-19, and 25-28 are under examination herein.
Priority
Application claims priority to 63/395,986 provisional application with an effective filing date of 8/8/22. Claims of the instant application are supported by the provisional application and thus have a priority date of 8/8/22.
Information Disclosure Statement
The IDS filed on 6/10/24 and 12/17/25 have been fully considered except where references have been lined through.
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 1, 4-5, 18, 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.
To show possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus (MPEP 2163). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species sufficient to show the applicant was in possession of the claimed genus (Id.). A “representative number of species” means that the species which are adequately described are representative of the entire genus (Id.). The specification describes Lys-Arg substitutions for the Lys-C of SEQ ID NO 2 (example 1). The substitution can be any type of substitution at any position along the ~470 amino acid sequence of Lys-C (SEQ ID 1 has 473 amino acids). Thus, the claims encompass a large and varied genus of polypeptides. The specification further fails to disclose any common mechanism or structure-function relationship that would allow one skilled in the art to identify conservative substitutions that enhance autolysis resistance. As such, the specification fails to describe a representative number of species that would evidence possession of the full scope of any conservative amino substitution along any Lys-C peptide.
Therefore, one of ordinary skill in the arts would be unable to immediately envisage the claimed product comprising conservative substitutions that enhance autolysis resistance. As such, the specification fails to describe a representative number of species that would evidence possession of the full scope of Lys-C conservative substitutions that enhance autolysis resistance.
Regarding claim 25, unlimited functional claim limitations that extend to all means or methods of resolving a problem may not be adequately supported by the written description or may not be commensurate in scope with the enabling disclosure, both of which are required by 35 U.S.C. 112(a) and pre-AIA 35 U.S.C. 112, first paragraph. As the claims require any conservative mutation that leads to the reduction of autolysis, the specification only provides support for the Lys-Arg substitution and no other conservative substitutions are described. Therefore, one of ordinary skill in the arts understands there is a nearly unlimited number of conservative substitutions that can be made which may or may not result in the reduced autolysis as there is not structure function relationship described in the specification. Further, there is no support in the specification describing how the many possible conservative substitutions lead to the claimed % enhancement.
Claim Rejections - 35 USC § 102
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)(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.
Claims 1, 4-7, 14, 18-19, and 26-28 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Anderson (WO1997033984A1 of record). Claim 18 is further evidenced by Shiraki, Kentaro, et al. ("Contribution of an imidazole-indole stack to high catalytic potency of a lysine-specific serine protease, Achromobacter protease I." The journal of biochemistry 131.2 (2002): 213-218).
Regarding claims 1 and 6, Anderson teaches protease variants from Achromobacter lyticus with substitutions at specific positions (abstract). Anderson teaches the Achromobacter lyticus protease is an endopeptidase (p1 last full paragraph). Anderson teaches the protease can comprise a lysine to arginine substitution (claim 7). Anderson teaches that this substitution reduces autoproteolysis (autolysis, p3 lines 21-22).
Regarding claims 4-5, Anderson teaches that the protease can be mutated at any one or more of positions 30, 49, 106, 155 and 203 (abstract).
Regarding claim 14 and 26-27, Anderson teaches the lysine can be replaced by a methyl moiety (claim 7).
Regarding claim 18, As evidenced by Shiraki figure 1, the points of 30, 49, 106, 155 and 203 in Anderson abstract are not found in the active site of the enzyme.
Regarding claim 19, Anderson teaches that a match to claimed SEQ ID NO. 4 (appendix). Mutating the points 30, 49, 106, 155 and 203 from Lys to Ala as taught by Anderson would generate a 100% match to claimed SEQ ID 4.
Regarding claim 28, Anderson teaches Achromobacter lyticus is a bacteria (p1 last full paragraph).
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Anderson (WO1997033984A1 of record). as applied to claims 1, 4-7, 14, 18-19, and 26-28 above, and further in view of Jiménez ("In‐gel digestion of proteins for MALDI‐MS fingerprint mapping." Current protocols in protein science 14.1 (1998): 16-4).
Regarding claim 25, Anderson teaches their substitutions diminishing the autoproteolysis of the enzyme (p3 lines 21-22).
Anderson does not quantify the amount of the reduction. While Anderson does not measure the amount of the reduction of the autoproteolysis, this property is a natural result of the activity of the modified enzyme and thus is not adding any more structural limitation to the claimed product. “Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable”. See MPEP 2112.
Jimenez teaches that during mass spec the autolytic peptides from the digestive enzymes can interfere with analysis including peptides from Lys-c (background information section).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to ensure that the enzyme of Anderson exhibits no autoproteolysis properties as taught by Jimenez. One of ordinary skill in the art would be motivated to do so because Jimenez teaches this can interfere with mass spec analysis. There would be a reasonable expectation of success as both Anderson and Jimenez are in the same field of endeavor of Lys-C.
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TREVOR L KANE whose telephone number is (571)272-0265. The examiner can normally be reached M-F 7:00 am-4:00pm.
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/TREVOR KANE/Examiner, Art Unit 1657
/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657