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 .
Claims 1-7 are pending.
Applicant’s election without traverse of a compound that read on
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in the reply filed on December 1, 2025 is acknowledged.
Claims 3-7 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.
Claims 1-2, drawn to a compound that read on
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, are being acted upon in this Office Action.
Priority
Applicant’ claim priority to provisional application 63/589,590, filed Oct 11, 2023, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 15, 025 has been considered by the examiner and an initialed copy of the IDS is included with this Office Action.
Drawings
The drawings filed on April 2, 2025 are acceptable.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over WO2022/246576 (published Dec 1, 2022; PTO 892) in view of Bargh et al (Chem Soc Rev 48: 4361-4374, 2019; PTO 892) and/or Jain et al (Pharm Res 32: 3526-3540, 2015; PTO 892).
Claim 1 encompasses a compound for use in synthesizing an antibody drug conjugate selected from the group consisting of
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Claim 2 encompasses the compound of claim 1, wherein the compound is
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.
The elected claimed compound comprises MC (Maleimidocaproyl) linked to a cleavable dipeptide Valine-Alanine linker to aminomethyl-Deruxtecan (Dxd) for making antibody drug conjugate.
Petersen teaches a compound such as MC-GGFG-AM-DXd for use in synthesizing an antibody drug conjugate, wherein the compound having the following structure:
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, see p. 222, para. [00855], [00870], Example 12, in particular.
Petersen further teaches that cleavable dipeptide linker Val-Ala cleaved by lysosomal protease once the conjugate internalized by a cell, see para. [030359], [00360], in particular.
Petersen does not teach the chemical structure of Val-Ala linker.
However, Bargh et al teaches antibody-drug conjugates (ADCs) comprising cleavable linkers, e.g., Val-Ala containing linker, which is effectively cleaved in cells and it is highly stable in human plasma, see p. 4370, left col. The Val-Ala unit has the following structure in box:
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The Val-Ala unit was first applied to ADCs in 2006 with highly potent Dox derivatives as payloads, see p. 4370, left col.
Likewise, Jain teaches the chemical structure of maleimidocaproyl (MC) attached to a protease-sensitive dipeptide, valine-alanine from Seattle Genetics, which in turn is attached to a drug PBD dimer, see p. 3531, 3533, structure reproduced below.
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In view of the combined teachings of the references, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to substitute Petersen’s peptide linker GGFG for Bargh’s or Jain’s dipeptide Val-Ala (VA) to arrive at the claimed chemical structure of MC-VA-AM-Dxd in order to form a stable antibody drug conjugate.
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One of ordinary skill in the art would have had an expectation of success at the time the invention was made to substitute a known peptide linker for another, e.g., protease sensitive linker Val-Ala because the dipeptide linker Val-Ala is stable and has been applied to ADCs in 2006 as taught by Bargh (see p. 4370) and/or Jain (see p. 3531). In addition, the claims would have been obvious because "a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense". See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
One of ordinary skill in the art would have been motivated to do so because Bargh et al teaches that antibody-drug conjugates (ADCs) comprising cleavable dipeptide linkers, e.g., Val-Ala is effectively cleaved in tumor cells and it is highly stable in human plasma, see p. 4370, left col.
One of ordinary skill in the art would have been motivated to do so because Jain teaches that the maleimidocaproyl (MC) protease-cleavable valine-alanine linker has been used to attached to the cysteine in the antibody for two phase I clinical trials, see p. 3231, left col.
“The test of obviousness is not express suggestion of the cl aimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them.” See In re Rosselet 146 USPQ 183, 186 (CCPA 1965).
“There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.,” Motorola, Inc, v. Interdigital Tech. Corn., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997).
Accordingly, the claimed invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-272-0839.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
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