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 the species of:
PNG
media_image1.png
172
587
media_image1.png
Greyscale
where Xa= -NHCH2; R = -CH2-CH2-COOH and t = 20
in the reply filed on 09/03/2025 is acknowledged.
Claims 1-48 are currently pending.
Claims 8-14, 16-22, 32-38 and 40-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 09/03/2025.
Claims 1-7, 15, 23-31, 39 and 47-48 will be examined on the merits.
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 4-7 and 29-31 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.
Claims 4-7 and 29-31 all contain the limitation that the L3 variable group is a spacer moiety having the structure –W—X--* (where * is the attachment point to R2). All of claims 4-7 and 29-31 also recite that W is permitted to be groups containing variables X and R2 including –CH2N(X-R2)C(=O)O--** and –C(=O)N(X-R2)--**, ( ** indicates the point to attachment to X for all). All of claims 4-7 and 29-31 also permits X to be a bond or several defined spacer moieties. All of claims 4-7 and 29-31 are rendered indefinite because including variables X and R2 within group W makes the claims subject to multiple interpretations: one wherein X and R2 is a structure found within W and one wherein X is a distinct group situated between X and R2. As such, the metes and bounds of claims 4-7 and 29-31 are unclear and claims 4-7 and 29-31 are indefinite.
Note: For the purpose of compact prosecution, compounds comprising W moieties that do not comprise variable groups R2 nor X will be considered further.
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.
Claim(s) 1-3, 23-27 and 47-48 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boghaert (Boghaert, et al., WO2017214282 A1; Published 12/14/2017; Priority to 6/8/2016 by way of US 62/347,416).
Boghaert discloses Bcl-xL inhibitor-comprising ADCs conjugated to anti-EGFR antibodies (Boghaert, Abstract). Boghaert discloses 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):
PNG
media_image2.png
208
557
media_image2.png
Greyscale
. Regarding claims 1-3 and 23-27, Example structure 2.145 of Boghaert satisfies all of the structural limitations of claims 1-3 and 23-27, with each of the variable moieties from the instant claims being indicated below:
PNG
media_image3.png
255
557
media_image3.png
Greyscale
Regarding instant claims 47-48, structure 2.145 of Boghaert satisfies claims 47-48 after conjugation to the anti-EGFR antibodies of Boghaert, with the conjugated maleimide crosslinker becoming R100 of claims 47 and 48.
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) 1-7, 23-31, 39 and 47-48 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) as applied to claims 1-3, 23-27 and 47-48 above and in further consideration of the Boghaert reference.
The teachings of Boghaert are discussed above.
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.
In addition to the teaching of Boghaert discussed above, Boghaert also teaches the linkers of Boghaert comprise formula (IVc) of Boghaert (Boghaert, claim 39):
PNG
media_image4.png
106
401
media_image4.png
Greyscale
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).
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. Please note that the resultant structure comprises the PEG carbonyl required for structure L1 of claims 4-7 and 28-31 as well as a val-cit peptidic moiety and reads on claims 4-7 and 28-31 as well.
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 reads on instant claim 39 as well.
Claim(s) 1-7, 15, 23-31, 39 and 47-48 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) as applied to claims 1-7, 15, 23-31, 39 and 47-48 above and in further view of Ou (Ou, et al., PLoS ONE 2018 13(10): e0206246).
The teachings of Boghaert are discussed above.
Boghaert does not teach that the drug unit of the drug-linker moiety of Boghaert is MMAE.
Ou teaches that the payload MMAE is an ADC payload that was known in the art to be ADC payload that can be attached val-cit-PAB self-immolative spacers via established chemistry (Ou, Fig. 1(b-d); p 4, ¶ 2).
It would be prima facie obvious to one of ordinary skill in the art to modify the drug-linker moiety taught by Boghaert discussed above to comprise the MMAE payload taught by Ou. The net result of this modification would be a drug-linker moiety identical to the drug-linker moiety of instant claim 15. One of ordinary skill in the art would be motivated to do this in order to form an ADC comprising a payload that is known in the art and is compatible with val-cit-PAB self-immolative spacers. One of ordinary skill in the art would have a reasonable expectation of success modifying the drug-linker moiety taught by Boghaert discussed above to comprise the MMAE payload taught by Ou because Ou teaches that MMAE payloads are known ADC payloads that are compatible with val-cit-PAB self-immolative spacers and may be attached to such spacers with known chemistry.
Conclusion
Claims 1-7, 15, 23-31, 39 and 47-48 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sydney Van Druff whose telephone number is (571)272-2085. The examiner can normally be reached 10 am - 6 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643