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 .
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 1-5, 7-9, 11-18, 20, 22 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. This rejection is maintained for reasons made of record in the Office Action dated 2/13/2026 and for reasons set forth below.
Response to Arguments
Applicant's arguments filed 5/12/2026 have been fully considered but they are not persuasive. Applicants essentially assert that: 1) according to Nguyen et al (2008), the skilled artisan would have known where mutations could have been made in the CYP2B protein without undue experimentation; 2) Wang et al (1997) teach the 3D structure of the recited NADPH p450 reductase, which would allow the skilled artisan to design functional mutations; 3) the claims have been amended to recite higher % identity values.
Regarding 1), the claims are not limited to substitutions or mutations in the binding region of CYP2B, and the claims already recite the substitutions taught by Nguyen et al to be beneficial, or at the least do not abrogate CYP2B expression or function. Beyond the specific residues studied by Nguyen et al, applicants assertion is an invitation for the skilled artisan to innovate CYP2B mutations that applicants have not disclosed.
Regarding 2), although Wang et al provide a starting point for the design of mutations, the reference (and the remaining relevant art) do not teach what specifically these mutations might be, particularly in light of the breadth of mutations claimed. As above, the claims are not limited to mutations in any given region or residue of the NADPH p450 reductase. Thus, applicants assertion, again, reads as an invitation for the skilled artisan to innovate what is not disclosed by the specification.
Regarding 1)-3), to put the situation in perspective, SEQ ID NO: 1 comprises 491 residues, of which 3 are specifically claimed as substituted, leaving the remaining 488 residues as possible substitution targets. In conjunction with the 85% identity language, 73 residues, at any location (other than the three recited in claim 1), may be changed to any other amino acid residue. SEQ ID NO: 2 comprises 621 residues and is claimed as having 90% identity. This translates to changing any of 62 residues, at any location, to any other given amino acid. The number of possible amino acid sequences that are of a given % identity relative to a reference sequence, where all differences between the possible sequences and the reference sequence are substitutions, can be calculated by the following formula: N = Xn . L!/ n! (L-(n-1)! where N is the number of possible sequences, X is the number of different residues that can be substituted for a residue in the reference sequence, L is the length of the reference sequence, n is the maximum number of residues that can be substituted relative to the reference sequence at a given % identity. For an amino acid sequence, X is 19 (alternate amino acids).
For a 488 amino acid sequence (SEQ ID NO: 1 is 491 residues, but 3 of these are defined by the claim and not subject to substitution) that is at least 85% identical to a reference sequence of 488 amino acids, the number of possible sequences having 73 amino acid substitutions relative to the reference is approximately 7.2 x 10178.
While limiting the scope of potential sequences to those that are at least 85% (or 90%, or 95%) identical to a reference, for example, greatly reduces the number of potential substitutions, it does not do so in any meaningful way.
The rejection of claims 11-13 as lacking enablement is withdrawn in view of applicants remarks and amendment of the claims.
Claim Objections
Claims 20 and 22 are objected to because of the following informalities: “…by trans-arterial route.” Should be “…by a trans-arterial route.”. Appropriate correction is required.
Allowable Subject Matter
Claims19 and 21 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
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 Michael Burkhart whose telephone number is (571)272-2915. The examiner can normally be reached M-F 8-5.
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/MICHAEL D BURKHART/ Primary Examiner, Art Unit 1638
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