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
Claims 23 and 49 are under consideration.
Rejections/Objections Withdrawn
All rejections of all cancelled claims are rendered moot by claim cancelation.
All 35 USC §§ 102 and 103 rejections have been withdrawn in view of claim amendments.
New Rejections Necessitated by Amendment
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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(s) 23 and 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boghaert (Boghaert, et al., WO2017214282 A1; Published 12/14/2017; Priority to 6/8/2016 by way of US 62/347,416, of record).
Boghaert teaches Bcl-xL inhibitor-comprising ADCs conjugated to anti-EGFR antibodies (Boghaert, Abstract). Boghaert teaches structure 2.145 of Boghaert, which is a drug-linker-crosslinker moiety that comprises the following structure prior to conjugation to the anti-EGFR antibody, with the structure containing a hydrophilic PEG moiety attached to a PABC spacer (Boghaert, p 268, Example 2.145):
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208
557
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(please note that the drug unit of Boghaert comprises 5 Ns and 4 Os and the point of attachment is an O).
Boghaert also teaches the linkers of Boghaert comprise formula (IVc) of Boghaert (Boghaert, claim 39):
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106
401
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Wherein:
The wavy line is the point of attachment to the drug
P = an integer from 0-5
q is 0 or 1
Ra is H, C1-6 alkyl, SO3H or CH2SO3H.
Ry is C1-4 alkyl-(N)((C1-4 alkylene)-G1))2
G1 is PEG4-32 or carboxy acid
Boghaert also teaches that the peptide present in formula (IVc) of claim 39 of Boghaert is permitted to be Val-Cit (Boghaert, Claim 40).
Boghaert does not teach that the structure 2.145 comprises a PEG carbonyl moiety between the maleimide crosslinker and the peptide moiety and wherein the peptide moiety is a valine-citrulline dipeptide. Boghaert does not teach that the hydrophilic moiety extending off PABC spacer comprises 24 PEG repeats, a -NHCH2- moiety and a terminal carboxy acid.
It would be prima facie obvious to one of ordinary skill in the art to modify the linker of Boghaert to comprise Formula (IVc) of Boghaert with Ra = hydrogen, peptide = val-cit, p = 1 and q = 0. One of ordinary skill in the art would be motivated to do this in order form a linker moiety for an ADC that is art equivalent to the linker moieties taught by Boghaert. One of ordinary skill in the art would have a reasonable expectation of success modifying the linker of Boghaert to comprise Formula (IVc) of Boghaert with Ra = hydrogen, peptide = val-cit, p = 1 and q = 0 because Boghaert teaches that hydrogen is permissible moiety for R1 of Formula IVc, val-cit is a permissible peptide moiety of Formula IVc and that 1 and 0 are permissible values for p and q of formula IVc, respectively.
It would be prima facie obvious to one of ordinary skill in the art to further modify the Ry moiety in the ADC linker discussed above to comprise a PEG24-COOH hydrophilic element and a (tertiary amine)-C(O)-NHCH2 spacer. One of ordinary skill in the art would be motivated to do this in order to form an ADC linker component art equivalent to the structure of Boghaert. Boghaert already teaches Ry moieties comprising a tertiary amine linked to two hydrophilic elements and that the hydrophilic elements are permitted to be PEG4-32 or COOH. As such, one embodiment encompassed by the teachings of Boghaert comprises a Ry moiety that is a tertiary amine linked to one PEG4-32 and one COOH. One of ordinary skill in the art would have a reasonable expectation of success modifying Ry to comprise a PEG chain terminated with a carboxy acid group because Boghaert teaches Ry moieties having a PEG chain and a carboxy acid on separate branches of a tertiary amine and one of ordinary skill in the art would reasonably expect moving the carboxy acid to the end of the PEG chain would add equivalent hydrophilicity. One of ordinary skill in the art would also have a reasonable expectation off success attaching the PEG-COOH chain by way of a -C(O)-NH2CH2 because this moiety is simply a means of attaching a first amine (the element attached to the PABC spacer) to a second amine (the element containing the PEG-COOH chain) by way of a carbonyl, which is within the purview of one of ordinary skill in the art as amine chemistry is one of, if not the most common attachment chemistries in bioconjugation chemistry. One of ordinary skill in the art would have a reasonable expectation of success picking 24 PEG repeat units because Boghaert 4-32 PEG repeat units and it is within the purview of one of ordinary skill in the art to start with the 4-32 PEG units taught by Boghaert and arrive at the claimed number of repeat units via routine experimentation to balance the added hydrophilicity vs added bulk per repeat unit. Additionally, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F. 2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) See MPEP 2144.05. Further with respect to optimal dosing regimens, it is not inventive to discover such regimens by routine experimentation when general conditions of a claim are disclosed in the prior art. See in re Aller, 220 F.2d 545, 456, 105 USPQ 233, 235 (CCPA 1955) and MPEP 2144.05(11). Please note that the resultant structure now fully satisfies structure (6) of claim 23 and structure (6) of claim 49.
Response to Arguments
Applicant's arguments filed 4/1/2026 have been fully considered but they are not persuasive.
Applicant’s arguments regarding the art rejection consisted solely of a statement that the instant claimed linkers as amended are structurally distinct from the linkers of Boghaert and that the prior art does provide motivation or suggestion to modify any of the linkers of Boghaert to arrive at the instant claimed linker structure. This argument is not persuasive because it was articulated in this and the prior Office Actions how the teachings of Boghaert render the instant claimed ADC structure obvious and Applicant has not argued against any of the rationale applied.
Conclusion
Claims 23 and 49 are rejected.
No claims are allowed.
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.
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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