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 . 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4 May, 2026 has been entered.
Election/Restrictions
Applicants elected X1-pGlu, X2=Tyr, X3=d-Lys, X4=Leu, X5=Arg, and R=CH2CH3 conjugated with MMAE to treat breast cancer without traverse in the reply filed on 18 Sept, 2024. In the submission of 4 May, 2026, applicants amended the claims so as to no longer read on breast cancer in general, limiting to specific subgenera.
Claims Status
Claims 1, 5-7, 21-26, 55, 61, 63, 64, and 74-82 are pending.
Claims 1, 26, 63, 79, and 80 have been amended.
Claims 81 and 82 are new.
Claims 5, 7, 21, 22, 55, 75, 63, 75-78, 81, and 82 have been withdrawn due to an election/restriction requirement.
Withdrawn Rejections
The rejection of claim(s) 1, 6, 23-26, 61, 63, and 74 under 35 U.S.C. 103 as being unpatentable over Nett et al (WO 90/09799, cited by applicants) in view of Schally (Peptides (1999) 20 p1247-1262) and Abdollahpour-Alitappeh et al (Novelty in Biomedicine (2017) 3 p98-103) is hereby withdrawn due to amendment.
New Rejections
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.
first rejection
Claim(s) 1, 6, 23, 24, 26, 61, 64, 74, 79, and 80 are rejected under 35 U.S.C. 103 as being unpatentable over Seitz et al (BMC Canc. (2014) 14:847) in view of Nett et al (WO 90/09799, cited by applicants).
Seitz et al discuss treatment of triple negative breast cancers with cytotoxic LHRH analogs (title). This analog is doxorubicin attached to D-lys6 LHRH (2nd page, 2nd column, 5th paragraph). Note that this differs from the compounds of the claims only in that the compound has a C-terminal Gly residue instead of a methyl or ethyl group. In other words, the only difference is that in applicant’s compounds, the C-terminal carboxylate has been reduced to a methyl group. In vivo experiments in mice with this compound were dissolved in 5% mannitol (4th page, 2nd column, 5th paragraph, based on control). This significantly inhibited the growth of the tumors (8th page, 1st column, 2nd paragraph, continues to 9th page, 1st column, 1st paragraph). The difference between this reference and the examined claims is a minor difference in the sequence of the peptide LHRH agonist.
Nett et al discuss methods for treating sex hormone related disorders, such as breast cancer (p1, 1st paragraph). This is done by conjugating toxins to GnRH (p9, 2nd paragraph), another name for LHRH. A most preferred peptide is pGlu-His-Trp-Ser-Tyr-dLys-Leu-Arg-Pro-ethylamide (p13, 1st paragraph). Note that the examples use a toxin conjugated with SPDP (linker)(p22, 4th paragraph). Other examples used carbodiimide (p24, 3d paragraph), which would make an amide (linker). Experiments were conducted in vivo in saline (p32, 3d paragraph). This reference discusses using a slightly different LHRH sequence than Seitz et al for similar purposes.
Therefore, it would be obvious to use the sequence of Nett et al in the therapy of Seitz et al, as a substitution of one known element (the sequence of Seitz et al) for another (the sequence of Nett et al) yielding expected results (binding to the receptor and treatment of cancer). As the two sequences are very similar, and are used for similar purposes, an artisan in this field would attempt this modification with a reasonable expectation of success.
Seitz et al discusses treatment of triple negative breast cancer with an LHRH analog attached to a cytotoxic agent. Nett et al renders obvious using the sequence pGlu-His-Trp-Ser-Tyr-dLys-Leu-Arg-Pro-ethylamide, rendering obvious claims 1, 6, 26, 79, and 80.
The cytotoxic agent is doxorubicin, rendering obvious claims 23 and 24.
The agent is dissolved in a mannose solution for administration, rendering obvious claims 61, 64, and 74.
second rejection
Claim(s) 1, 6, 23-26, 61, 64, 74, 79, and 80 are rejected under 35 U.S.C. 103 as being unpatentable over Seitz et al (BMC Canc. (2014) 14:847) in view of Nett et al (WO 90/09799, cited by applicants), Abdollahpour-Alitappeh et al (Novelty in Biomedicine (2017) 3 p98-103, previously cited), Vranic et al (Oncol. Lett. (2011) 2 p1131-1137) and Lanning et al (Canc. Metabol. (2017) 5:6)
Seitz et al discuss treatment of triple negative breast cancers with cytotoxic LHRH analogs (title). This analog is doxorubicin attached to D-lys6 LHRH (2nd page, 2nd column, 5th paragraph). Note that this differs from the compounds of the claims only in that the compound has a C-terminal Gly residue instead of a methyl or ethyl group. In other words, the only difference is that in applicant’s compounds, the C-terminal carboxylate has been reduced to a methyl group. In vivo experiments in mice with this compound were dissolved in 5% mannitol (4th page, 2nd column, 5th paragraph, based on control). This significantly inhibited the growth of the tumors (8th page, 1st column, 2nd paragraph, continues to 9th page, 1st column, 1st paragraph). Nett et al discuss methods for treating sex hormone related disorders, such as breast cancer (p1, 1st paragraph). This is done by conjugating toxins to GnRH (p9, 2nd paragraph), another name for LHRH. A most preferred peptide is pGlu-His-Trp-Ser-Tyr-dLys-Leu-Arg-Pro-ethylamide (p13, 1st paragraph). Note that the examples use a toxin conjugated with SPDP (linker)(p22, 4th paragraph). Other examples used carbodiimide (p24, 3d paragraph), which would make an amide (linker). Experiments were conducted in vivo in saline (p32, 3d paragraph). This reference discusses using a slightly different LHRH sequence than Seitz et al for similar purposes.
As noted above, these references render obvious claims 1, 6, 23, 24, 26, 61, 64, 74, 79, and 80.
The difference between these references and the remaining claim is that they do not discuss MMAE as the cytotoxic agent.
Abdollapour-Alitappeh et al discuss MMAE as a cytotoxic payload for conjugates to treat breast cancer (title). MMAE is a very potent chemotherapeutic, commonly used as part of a conjugate to treat breast cancer (p99, 1st column, 4th paragraph). This potency against breast cancer is demonstrated by the authors (p102, 2nd column, 2nd paragraph) against MDA-MB-468 and MD-MB-453 cell lines (p99, 1st column, 5th paragraph, continues to 2nd column, 1st paragraph). Note that these are triple negative breast cancer cell lines (Lanning et al, 2nd page, 2nd column, 2nd paragraph and Branic et al, abstract). This reference teaches that MMAE is a potent toxin for use in conjugates against triple negative breast cancer.
Therefore, it would be obvious to use MMAE in the construct of Seitz et al and Nett et al as a substitution of one known element (the doxorubicin of Seitz et al) for another (the MMAE of Abdollapour-Alitappeh et al) yielding expected results (treatment of the tumor). As Abdollapour-Alitappeh et al show that this therapeutic is effective on triple negative breast cancer cell lines, an artisan in this field would make this substitution with a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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