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 1 has been canceled. Claims 2-5, 7-16, 19, 20 and 21 have been amended. Claims 22- and 23 have been added. Claims 2-23 are pending and under consideration.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e)as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No.63/339,784, 63/277,245 and 63/237,663, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Application 63/237,663 fails to provide a written description for either of the radioimmunoconjugates required in claims 1, 13, and 14.
Application 63/277,245 fails to provide a written description of the radioimmunoconjugate
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Accordingly, claims 2, 3-12 and 15-21 will be considered to have the effective filing date of 5/9/2022 commensurate with the filling date of the 63/339,784 application commensurate with the first written description of both radioimmunoconjugates as well as the CDR sequences of anti-PSMA antibody now required.
Claims 13 and 22 will be considered to have the effective filing date of 11/9/2021 as both of the structure of the immunoconjugate and the CDR sequences of anti-PSMA antibody are described in the 63/277,245 application.
Claims 14 and 23 will be considered to have an effective filing date of 5/9/2022 as both of the structure of the immunoconjugate and the CDR sequences of anti-PSMA antibody are described in the 63/339,784 application.
The rejection of claims 2-21 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 is withdrawn in light of applicant’s amendment.
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.
Claims 2, 5-12, 14-21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Bander et al (WO2002/098897) in view of Wu et al (Bioconjugate Chemistry, 2016, Vol. 27, pp. 2460-2468) and Desjarlais et al (U.S. 2023/0265218, priority to 2/23/2022).
Bander et al teach anti-PSMA antibodies which are de-immunized and carrying a human IgG1 and κ light chain (paragraph [00164]), which meets the limitation of claims 5 and 6.
Bander et al teach the conjugation of an anti-PSMA antibody (abstract) to the chelator, DOTA, by reacting antibody lysines with the active ester formed from DOTA and NHS (page 118):
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Bander et al teach that radioisotopes useful as therapeutic agents, as opposed to diagnostic agents or labels, include actinium-225, astatine-211, and bismuth-213, which meets the same limitations in claim 1.
Bander et al teach a method for treating a prostatic cancerous disorder in a subject comprising administering an inventive antibody coupled to a radioactive isotope (Claim 25 and 28 of ‘897) which meets the limitation of instant claims 16 and 17. Bander et al teach the treatment of hormone refractory prostate cancer with metastatic disease (paragraph [00427]), which meets the limitations of claim 18.
Bander et al teach a method for detecting PSMA protein in a sample, including serum or urine, comprising contacting the sample with the inventive modified anti-PSMA antibody, wherein formation of a complex with the antibody is indicative of the presence of a PSMA protein and can be an indicator of a need for treatment with the inventive method (paragraph [0081]). Thus, the method of Bander et al is inherently a method for detecting a PSMA expressing cancer as in claims 19 and 20.
Bander et al teach kits comprising a chelator conjugated antibody and instructions for performing the radiolabeling procedure (paragraph [00242]) which meets the limitations of claim 21. Bander et al teach pharmaceutical compositions comprising the inventive antibodies and a pharmaceutically acceptable carrier (paragraph [0063]) which meets the limitations of claim 15.
Bander et al do not teach the anti-PSMA conjugated to the chelator:
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Wu et al teach that the past methods of conjugating linkers to monoclonal antibodies relies on the either the ε-lysine of the native antibody or antibody thiols (page 2460, first column, lines 11-13). Wu et al teach that because antibodies possess approximately 40 lysine and 8 cysteine residues, this conventional conjugation produces heterogenous mixtures with respect to conjugate ratios and sites of conjugation (page 2460, first column, lines 14-17). Wu et al teach that the biological activities and plasma half-lives may be decreased when conjugation occurs at the antigen binding sites or in the Fc domain, and that different conjugate rations can affect the pharmacokinetics and toxicity of the product (page 2460, bridging sentence between the 1st and 2nd column, and column 2, lines 1-3) Wu et al teach that bath-to-batch reproducibility is often difficult to achieve for these heterogenous products (page 2460, second column, lines 3-5).
Wu et al teach the engineering of rituximab to express an azide bearing unnatural amino acid at A122 of the heavy chain, and the subsequent cycloaddition of the azide to a DIBO-DOTA linker-chelate:
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to provide:
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Wu et al teach that the method controlled the chelator load location and chelator to antibody ratios which provides batch-to-batch consistency thus avoiding potential risks of non-selective conjugation including decreased antigen-affinity and changes in pharmacokinetics (page 2465, first column, lines 8-15). Wu et al teach other sites for potential modification include K278, E322, R359 and K396 on the heavy chain and K168 on the light chain (page 2462, first column, lines 2-5).
It would have been prima facie obvious at the time prior to the effective filing date to modify an anti-PSMA antibody of Bander et al to express of the azidoethyloxycarbonyl-L-lysine at a defined amin acid residue; and to conjugate the modified antibody to the linker-chelate of DIBO-DOTA, followed by reaction with the radiometal salt. One of skill in the art would have been motivated to do so because Bander et al teach the conjugation of the active ester of DOTA to the native lysine residues of the antibody and Wu et al teach that antibodies have approximately 40 lysine residue available for conjugation leading to a heterogenous mixture prone to batch-to-batch variation that could decrease antigen binding, and alter pharmacokinetics. One of skill in the art would have been motivated to overcome these effects to improve the clinical reliability of the antibody.
Regarding the anti-PSMA antibody having the CDRs of claim 2 section (i), it is noted that neither Bander et al nor Wu et al teach an anti-PSMA antibody comprising the heavy and light chain CDRs of SEQ ID NO: 272-274 and 275-277 as in instant claim 2(i).
Bander et al teach that the expression of human PSMA is substantially lower on non-malignant prostate cells (paragraph [0014]).
Desjarlais et al teach an anti-PSMA antibody comprising a variable heavy chain of SEQ ID NO: 246 paired with a variable light chain of SEQ ID NO: 250 (page 258, paragraph (b), page 259(b) in 63/313,233); and a variable heavy chain of SEQID NO: 294 paired with a variable light chain of SEQ ID NO: 298(page 258, second column, paragraph (12), page 260(12) in 63/313,233).
The instant heavy chain CDRs of SEQ ID NO: 272, 273 and 274 are present in
the variable heavy chain of SEQ ID NO: 246:
EVQLLESGPGLVKPSETLSLTCTVSGGSIISYYWSWIRQPAGKGLEWIGRIYSSGSTNYNPSLKSRVTMS VDTSKNQFSLKLSSVTAADTAVYYCAKVGVWPGAFDIWGQGTMVTVSS
and the instant CDRs of SEQ ID NO: 275, 276 and 277 are present in in the variable light chain of SEQ ID NO: 250:
QSVLTQPPSASGTPGQRVTISCSGSSSNIGSNTVNWYQQLGTAPKLLIYSSNQRPSGVPDRFSGSKSGT SASLAISGLQSEDEADYYCAAWDDSLNGVVFGGGTKLTVL
The instant heavy chain CDRs of SEQID NO: 34, 35 ad 36 are present in the variable heavy chain of SEQ ID NO: 294:
QVQLQESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVAFISYDGSNKYYADSVKGRFTI SRDNSKHTLYLQMNSLRAEDTAVYYCAGRDNLRFLEWFMDVWGQGTTVTV
and the instant light chain CDRs of SEQ ID NO: 37, 38 and 39 are present in the variable light chain of SEQ ID NO: 298:
EIVLTQSPGTLSVSPGERATLSCRASQSVRSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTE FTLTISSLQSEDFAVYYCHQYNDWPPYTFGQGTKLEIK
Desjarlais et al teach that the inventive anti-PSMA antibodies are active on PSMA high and PSMAmed expressing cells(paragraph [01509]).
Desjarlais et al teach that the Fc domains each comprise one or more ablation variants, wherein one or more ablation variants comprise L234A/L235A/D265S (paragraph [0305]), which meets the limitations of claims 7-9.
Desjarlais et al teach that the Fc domains each further comprise amino acid substitutions M252Y/S254T/T256E, wherein the amino acid substitutions of M252Y/S254T/T256E are half-life extension variants (paragraph [0649]), which result in a longer half-life in serum (paragraph [0668]), meeting the limitations of claims 11-12.
It would have been prima facie obvious at the time prior to the effective filing date to use any of the anti-PSMA antibodies, including the antibodies comprising the heavy and light chain variable regions of SEQ ID NO:246/250 and 294/298 of Desjarlais et al in the radioimmunoconjugate targeting PSMA rendered obvious by the combined teachings of Bander et al and Wu et al. One of skill in the art would have been motivated to do so because Bander et al teach that PSMA is expressed on normal cells at a lower level than on malignant cells, and because Desjarlais et al teach that the inventive anti-PSMA antibodies are active on PSMA high and PSMAmed expressing cells. One of skill in the art would understand that the anti-PSMA antibodies of Desjarlais et al would bind malignant cells rather than normal cells expressing PSMA. One of skill in the art would be motivated to use such an anti-PSMA antibody for the immunoconjugate in order to avoid toxicity to normal tissues.
Applicant argues that Desjarlais et al is not prior art to amended claim 2 because 63/237,663 provides a written description of the antibody recited in claim 2, sections a to i. This has been considered but not found persuasive. As stated above, application 63/237,663 fails to provide a written description for either of the radioimmunoconjugates required in claims 1, 13, and 14. Thus, claims 2, 5-12, 14-21 and 23 are considered to have the effective filing date of 5/9/2022 commensurate with the filling date of the 63/339,784 application commensurate with the first written description of both radioimmunoconjugates as well as the CDR sequences of anti-PSMA antibody now required.
Applicant further argues that the instant claims are not drawn to an anti-PSMA antibody comprising a VH or SEQ ID NO: 246 paired with a VL of SEQ ID NO: 250; or a VH of SEQ ID NO: 294 paired with a VL of SEQ ID NO: 298. This has been considered but not found persuasive. The instant claims rendered obvious by Desjarlais et al require an anti-PSMA antibody having, in part, a VH comprising the CDRS of SEQ ID NO: 273, 274 and 275, paired with a VL comprising SEQ D NO: 275, 276, 277 as in claim 2, section i), or a VH comprising the CDRS of SEQ ID NO: 34, 35 and 36 paired with a VL comprising the CDRs of SEQ ID NO: 37, 38 and 39 as in claim 2(f) which are taught by Desjarlais et al.
All other rejections and/or objections as set forth in the prior Office action are withdrawn.
Allowable Subject Matter
Claim 13 is allowed.
Claims 3, 4 and 22 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 KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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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.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/ Primary Examiner, Art Unit 1643