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 .
Claims 3-7, 9-12, and 14 have been amended. Claims 16 and 17 have been added. Claims 1-17 are pending and examined on the merits.
Claim Objections
Claim 1, 4, 6, 14 objected to because of the following informalities:.
the structures
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, and
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in claim 1 are blurry;
the structure
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in claim 6 is blurry; and
the structure
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in claim 14 is blurry.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 6 describes an ADC comprising brentuximab. Claim 6 is dependent on claim 1. Clam 1 requires that the antibody drug conjugate is an anti-CD56 antibody. Thus, claim 6 fails to include all the limitations of claim1 on which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 3, 8-10, 12 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.
Regarding claims 10, 12, and 17, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 3, 8, 9, 12, 13 and 17, it is unclear how the description of a species as “preferable” influences the metes and bonds of the claims.
Regarding claim 9, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 10 is vague and indefinite in the recitation of “doxorubicin and/or cyclophosphamide”. It is unclear in the case of “or” if the cyclophosphamide is selected to the exclusion of doxorubicin.
Claim 14 is vague and indefinite in the recitation of “advantageously” equal to 4 or 5. it is unclear how the description of a species as “advantageous” influences the metes and bonds of the claims.
Claim 10 is vague and indefinite in the recitation of “etoposide and/or an antibody”. It is unclear in the case of “or” if the antibody is selected to the exclusion of etoposide.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claims 1-4, 7, 8, 11, 14, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Joubert et al (WO2015/004400, reference of the IDS filed 8/25/2022) as evidenced by US 10,307,488 (English Language Translation) in view of Miao et al (WO2013/173391).
Joubert et al teach antibody drug conjugates comprising linkers wherein the linker comprises a linker head and a linker body, and a method of preparing said linkers (abstract). Joubert et al teach that the antibody drug conjugates comprise a connection to an antibody, a polarity region, a trigger a suicide spacer and a drug (Figure 1). Joubert et al teach the linker 22 (columns 47-48) wherein the linker head is pyridine, having two branches terminate in Bromine, a polarity region and a Val-Cit dipeptide and a p-amino benzyl alcohol:
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which meets the limitations of claim 1 for a conjugation head which is
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, wherein m is 5; a cleavable linker which is
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, and a spacer which is
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.
Joubert et al teach that a preferred antibody of the conjugate includes anti-CD56 antibody (column 22, line 60) which meets that limitation of claim 1. Joubert et al teach a general procedure wherein a solution of the desired antibody is reduced by TCEP and the linker is added (column 50, lines 40-51). One of skill in the art would understand that the free thiol of the reduced antibody would react with the linker resulting in a substitution of the antibody thiol for the bromine. Joubert et al teach an example using the same linker but with an analogous linker head,
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is reacted to form an adduct with MMAE (columns 39-40, structure 9-MMAE)
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which meets the limitation of claim 14 for the linker comprising
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the spacer of
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, and claim 15 for reaction with MMAE 6-(2,6-bis(bromomethyl)pyridine-4-yl)amido-N-hexanamide-valine-citrullline-p-aminobenzoyl carbamate, reacted with the preferred anti-CD56 antibody. Joubert does not specifically teach the derivation of compound 22 to form an adduct with MMAE, the number for “n”, the DAR, or the “use” of a composition comprising the antibody-drug conjugate of claim 1 as a drug or for use in the treatment of a CD56+ cancer.
Miao et al teach an analogous antibody-linker-drug conjugate:
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wherein, the linker head differs from the instant linker head, and wherein the carbon adjacent to the exocyclic secondary amine does not carry a carbonyl group (claim 6 of ‘127, column 117). Miao et al teach that drug-conjugates include a multifunctional linker providing a 2-5 atom bridge (column 4, lines 23-24). Miao et al teach that the structural integrity of an antibody can be compromised after opening disulfide bonds and attaching payloads to the exposed free thiols and the compositions and method disclosed provide conjugation through cysteine without decreased structural stability (column 4, lines 32-36). Miao et al teach that the number of molecules of drug attached to the antibody through the multifunctional linker can range from 1-10 (claim 1 of ‘127 , n=1,2,3,4,5,6,7,8,9 or 10) which meets the limitations of claim 8. Miao et al teach a method of treating a patient with cancer comprising administering an active agent-conjugate as disclosed (column 11, lines 19-22) thus meeting the limitations of claim 11 for use as a drug.
It would have been prima facie obvious at the time prior to the effective filing date to react the linker 22 of Joubert et al to form a linker-drug with MMAE and to react the linker-MMAE with the TCEP reduced anti-CD56 antibody. One of skill in the art would have been motivated to do so because Miao et al formed an antibody conjugate with a highly similar linker attached to MMAE. Miao et al teach that the linker head provides a 2-5 atom bridge and prevents antibody destabilization after reduction and loading of payloads.
Claims 1-8 and 10-17 are rejected under 35 U.S.C. 103 as being unpatentable over Joubert et al and Miao et al as applied to claims 1-4, 7, 8, 11, 14, 15 and 16 above, and further in view of Dimitrov et al (WO2017/023780, reference of the IDS filed 8/25/2022).
Claim 5 requires that A is m906.
Claim 6 specifies, in part, that the antibody drug conjugate of
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Claim 9 requires that the DAR is between 3.5 and 4 in the composition of claim 7.
Dimitrov et al teach a method of treating a subject having a CD56-positive cancer, comprising selecting a subject with a CD56-positive cancer and administering to the subject a therapeutically effective amount of the ADC of claim 1 (claim 28 of ‘568).wherein the CD56-positive cancer is a neuroblastoma, multiple myeloma, ovarian cancer, acute myeloid leukemia, Wilms tumor or small cell lung cancer (claim 30 of ‘568) which meets the limitations of claims 12 and 13. Dimitrov et al teach that the m906 antibody comprises the variable heavy chain domain of SEQ ID NO: 6 (paragraph [0039]) and the variable light chain domain of SEQ ID NO: 8 (paragraph [0041]). Thus claim 1 of ‘568 encompasses the m906 anti-CD56 antibody).. Dimitrov et al teach that the antibodies of the invention can be administered as ADC and that any suitable anti-cancer agents can be administered in combination with the immunoconjugates (paragraph [0207]), such as cyclophosphamide (paragraph [0208]), etoposide (paragraph [0210]) and docetaxel (paragraph [0212]). Which meet the limitations of claim 10.
It would have been prima facie obvious at the time of the effective filing date to use the m906 antibody and composition comprising the m906 antibody in combination with cyclophosphamide, etoposide or docetaxel of Dimitrov et al as the anti-CD56 antibody of Joubert et al.. One of skill in the art would be motivated to do so because Dimitrov et al teaches that the m906 antibody is suitable for admisntration as an ADC, and cyclophosphamide, etoposide or docetaxel can be administered in combination with the immunoconjugate. It would have been prima facie obvious to use the ADC rendered obvious by the combined teachings of Joubert et al and Miao et al in a method of treating CD56+ cancers such as acute myeloid leukemia, and small cell lung cancer because Dimitrov et al teach m906 ADCs used for the treatment of these cancers.
Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Joubert et al, Miao et al and Dimitrov et al as applied to claims 1-8 and 10-17 above, and further in view of Khera and Thurber (BioDrugs, 2018, Vol. 32, pp. 465-480).
The combined teachings of Joubert et al, Miao et al and Dimitrov render obvious claims 1-8 and 10-17 for the reasons set forth above.
Regarding claim 9, Miao et al teach that different DAR can be obtained by using different ratios of drug to antibody in the conjugation reaction (column 107, lines 28-46).
Khera and Thurber teach that higher DAR are known to exhibit faster systemic clearance owing to the removal of the high DAR agent from circulation due to high hydrophobicity of the payload (page 469, second column, lines 8-12 of the bottom paragraph). Thus, one of skill in the art would be motivated to optimize the DAR is order to avoid fast systemic clearance. One of skill in the art would understand that fast systemic clearance would limit therapeutic efficacy. Thus, one of skill in the art would have been motivated to optimize the DAR by controlling the ratio of the drug to antibody in the conjugation reaction based on the teachings of Miao et at to arrive at an optimized DAR between 3.8 and 4 which would provide a therapeutic level of drug delivery.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 4, 5, 6, 7, and 10-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 18/333,261(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘261 application anticipate the instant claims.
Claims 12, 14, and 16 anticipate claims 1, 4, 6, respectively. Claims 13, 15 and 17-21 ender obvious instant claims 3, 5, 7, 10-13 to the extent that claim 1 of the ‘261 application encompasses the structure of claim 12.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
All claims are rejected.
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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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643