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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 28 Aug, 2025 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.
Claims Status
Claims 1, 5-7, 21-26, 55, 61, 63, 64, and 74-80 are pending.
Claim 61 has been amended.
Claims 5, 7, 21, 22, 55, 75, 64, and 75-80 have been withdrawn due to an election/restriction requirement.
Withdrawn Objections
The objection to claims 1, 61, 26, and 74 as duplicate pairs is hereby withdrawn due to amendment and argument.
Maintained/Modified 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.
Claim(s) 1, 6, 23-26, 61, 63, and 74 are rejected 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).
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). 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).
The difference between this reference and the examined claims is that this reference does not mention MMAE and looks at a slightly different patient population.
Schally et al discuss LHRH (another name for the GnRH of Nett et al) analogs for treating tumorigenesis (title). The compound can work by inhibiting pituitary and gonadal activity (abstract), similar to the mechanisms discussed by Nett et al, but also talks about using toxin conjugated analogs of the hormone to directly target the receptor expressed on cancers, including breast cancer (p1251, 1st column, 2nd paragraph, continues to 2nd column). This reference discusses direct targeting by LHRH of chemotherapeutic agents to cancers.
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). This reference teaches that MMAE is a potent toxin for use in conjugates against breast cancer.
Therefore, it would be obvious to use the materials of Nett et al to treat the cancers of Schally et al, as Schally et al shows that functionally equivalent materials are used for that purpose.
Therefore, it would be obvious to use the MMAE of Abdollapour-Alitappeh et al instead of the toxins of Nett et al in the conjugates of Nett et al, to treat breast cancer, as Abdollapour-Alitappeh et al state that this therapeutic is a common one for this purpose, and Schally teaches that the peptide of Nett et al will direct the toxin to the tumor. As Abdollapour-Alitappeh et al state that this toxin is commonly used in conjugates for treating breast cancer, an artisan in this field would attempt this substitution with a reasonable expectation of success.
Nett et al and Schalley et al discuss using LHRH conjugated to a cytotoxic agent to treat cancer, with Schalley et al discussing LHRH positive cancers. Nett et al discusses a sequence pGlu-His-Trp-Ser-Tyr-dLys(drug)-Leu-Arg-Pro-NH-CH2CH3. Nett et al gives an example of a pharmaceutically acceptable excipient formulation. Thus, the combination of references renders obvious claims 1, 6, 26, 61, and 74.
Abdollapour-Alitappeh et al render obvious using MMAE as the cytotoxic agent, rendering obvious claims 23-25.
Nett et al and Schalley et al both discuss breast cancer, rendering obvious claim 63.
response to applicant’s arguments
Applicants argue that the peptides of Nett et al and Schalley et al are not equivalents, that Schally et al does not teach that the peptide of Nett et al will direct toxin to the tumor, that Abdollapour-Alitappeh et al does not teach MMAE will work in the claimed conjugates, and that none of the cited references teach the claimed peptide for LHRH receptor expressing cancer.
Applicant's arguments filed 28 Aug, 2025 have been fully considered but they are not persuasive.
Applicants argue that the sequences of Nett et al and Schally et al are not functional equivalents. Applicants attempt to show a list of differences between different LHRH sequences to argue a lack of equivalence. However, both Nett et al and Schalley et al discuss attaching a drug to an LHRH sequence to direct the drug to a receptor. Each sequence performs the same function (binding to the receptor with a payload) in essentially the same way and produces substantially the same result; this leads to a finding of equivalence (MPEP 2183). Note that equivalence does not mean all properties are identical; the fact that some properties are different, as applicants have noted, does not mean non-equivalence unless such properties indicate that the different sequences do not perform the same functions (MPEP 2184(II)).
Applicants next argue that Schalley et al does not teach that the sequence of Nett et al will direct a toxin to a tumor. Both Schalley et al and Nett et al discuss binding to LH-HR receptors; Schalley et al explicitly mentioning such receptors expressed by breast cancers (p1251, 2nd column, 1st paragraph). A person of skill in the art would reasonably conclude that the peptide of Nett et al would be effective in the process of Schalley et al. Note that if Schalley et al had mentioned the sequence of Nett et al could target the receptor on cancer, that reference would have anticipated at least one claim.
Applicants argue that Abdollahpour-Alitappeh et al does not teach that the claimed sequence will bring MMAE to a cancer. Applicants have pointed to as many differences as they can find between the teachings of this reference and their claimed invention. However, there is no explanation of why these differences would lead a person of skill in the art to assume that conjugation of MMAE to an LHRH agonist peptide would be ineffective in treating an LHRH expressing cancer.
Finally, applicants argue that none of the cited references discuss the claimed peptide for treating LHRH positive breast cancer. While true, this does not invalidate the rejection, as all the elements are found in the various cited references, along with a rationale to combine the elements. If a reference had discussed the claimed conjugate for treating the claimed disorder, it would anticipate the claims.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 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