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 1-19 are under consideration.
Claim Objections/Rejections Withdrawn
The objections to claims 1, 3 and 5-8 as well as the objections to the Specification and Drawings have been withdrawn in view of claim amendments and the substitute Specification of 11/24/2025, which remedies both the illegible figures and the amino acid sequences without SEQ ID NOs:
All 35 USC § 112(b) rejections have been withdrawn in view of claim amendments.
Rejections Maintained/New Rejections Necessitated by Amendment.
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 1-19 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.
Claim 1
Claim 1 recites a tubulysine analog of Formula (II)
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Claim 1 recites that the dashed lines in the figure above indicate “a linkage site that links to W independently, D links to W or L1 or L2 when absent….. via at least one ------ of R1, R2, R7, R8, R9, R12, R13, and R14”. All of R1, R2, R7, R8, R9, R12, R13 and R14 are attached to dashed lines. Claim 1 recites that the linkage to W is selected from at least one of of the dashed lines, allowing for the possibility of multiple linkages to W via multiple R groups up to bonds between all of R1, R2, R7, R8, R9, R12, R13, and R14 and W, but it is also not possible for this many of these R groups to simultaneously form linkages to W and still also comprise the recited moieties. Also, it not clear what the of R1, R2, R7, R8, R9, R12, R13 and R14 groups link to via their respective dashed lines when they do not link to W.
Response to Arguments
This is a new rejection necessitated by amendment and no arguments supplied apply to it.
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 7 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 7 is dependent on claim 1. Claim 7 recites several structures comprising two linear moieties, each of which connect at one end to the same mAb and connect at the other end to the same aromatic moiety, with the two linear moieties having a covalent “bridge” connecting the two linear moieties. One of these structures from claim 7 is depicted below with a red arrow pointing to the covalent “bridge”:
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As stated above, claim 7 is dependent on claim 1 and all of the compounds of claim 1 satisfy Formula (III) of claim 1:
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In the example structure from claim 7 above, the mAb corresponds to T, the two linear moieties are (L1-V1) and (L2-V2), the PEG chains that branch off of the two linear moieties correspond to Q1 and Q2, the aromatic ring corresponds to W and the tubulysin that the aromatic ring connects to corresponds to D. Claim 7 does not contain all of the limitations of claim 1 because claim 1 does not allow for direct, covalent linkages between (L1-V1) and (L2-V2).
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.
Response to Arguments
No arguments were supplied for this rejection.
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, 4, 8, 10-16 and 19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burke (Burke, et al., WO 2017/096311 A1; Published 06/08/2017; Priority to 12/4/2015 by way of US 62/263,578).
Burke discloses drug-linker-crosslinker moiety 95 of Burke (Burke, ¶ 1298), which was conjugated to the anti-CD30 antibody cAC10, with the resultant ADC having an IC50 of 0.8 ng/mL against L540cy Hodgkin’s lymphoma cells (Burke, ¶ 1441):
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Regarding claim 1, the ADC of Burke fully satisfies the limitations of Formula III of claim 1 when T is the anti-cAC10 antibody, V2, L2, and Q2 are absent, the crosslinker is V1, the peptide moiety is L1, the PEG moiety is Q1, the PAB moiety is W, and the tubulysin of Burke is D (with the heterocyclic ring being formed when R2 and R4 come together to form the heterocycloalkyl ring and wherein R1 is absent, thus making the N link directly to W). Regarding claim 4, the tubulysin of Burke reads on tubulysin I-51 (presumed to be unconjugated tubulysin). Regarding claim 8, antibody cAC10 is a cell binding agent that is an antibody. Regarding claims 10-11 antibody cAC10 of Burke is capable of targeting tumor cells that are L540cy Hodgkin’s lymphoma cells. Regarding claim 12, Burke discloses pharmaceutically acceptable formulations comprising excipients (Burke, claims 93-94). Regarding claim 13, Burke discloses formulations comprising at least 0.01% of the conjugates of Burke by weight (Burke, ¶ 0480). Regarding claim 14, Burke discloses enclosing the pharmaceutical compositions of Burke in syringes (Burke, ¶ 0478). Regarding claim 15, the ADC of Burke exhibits in vitro cell killing activity vs L540cy Hodgkin’s lymphoma cells (Burke, ¶ 1441). Regarding claim 16, Burke discloses simultaneous administration of a chemotherapeutic agent and the conjugate of Burke (Burke, ¶ 0469-0470).
Response to Arguments
Applicant's arguments filed 11/24/2025 have been fully considered but they are not persuasive.
Applicant’s arguments are based on the fact that a quaternary amine is present in as the “Y1” moiety in the D moiety (see claim 1). This is not persuasive as both R1 and R2 are permitted to be alkylcarbocycles and, as such, quaternary amines are encompassed by the absurdly large Markush grouping when the alkylcarbocycle comprises a alkyl adjacent to the N.
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, 4, 8, 10-17 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Burke (Burke, et al., WO 2017/096311 A1; Published 06/08/2017; Priority to 12/4/2015 by way of US 62/263,578) as applied to claims 1, 4, 8 and 10-16 above and in further view of Mattes (Mattes, et al., Swiss Med. Weekly 2017 147:w14487).
The teachings of Burke are discussed above.
Burke does not teach the simultaneous administration of the conjugates of Burke and a chemotherapeutic that is cyclophosphamide.
Mattes teaches that cyclophosphamide is a commonly prescribed single agent for non-Hodgkin’s lymphoma (Mattes, p1, ¶ 5, p 2, ¶ 1).
It would be prima facie obvious to one of ordinary skill in the art to combine the ADC of Burke and the cyclophosphamide of Mattes with the net results being a pharmaceutical composition comprising the ADC of Burke and cyclophosphamide that is administered to treat non-Hodgkin’s lymphoma. One of ordinary skill in the art would be motivated to do this in order to better treat non-Hodgkin’s lymphoma. One of ordinary skill in the art would have a reasonable expectation of success formulating a pharmaceutical composition comprising the ADC of Burke and cyclophosphamide that is administered to treat non-Hodgkin’s lymphoma because Burke teaches simultaneous administration of a chemotherapeutic and the ADC of Burke and that the ADC of Burke was able to selectively kill non-Hodgkin’s lymphoma cells and cyclophosphamide is also an agent that can treat non-Hodgkin’s lymphoma.
Response to Arguments
Applicant's arguments filed 11/24/2025 have been fully considered but they are not persuasive. Applicant grouped the arguments for the 102 and 103 rejections together and, as such, have already been addressed.
Conclusion
Claims 1-19 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.
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.
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643