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 .
Election/Restrictions and Claim Status
Applicant’s election without traverse of species 80 in the reply filed on 8/7/26 is acknowledged.
The species as depicted in the response is not the same as what is depicted for species 80 on page 29 of the specification. Specifically, the N-MeVal of MMAE does not include a carbonyl oxygen. The elected species of claim 80 is interpreted consistent with what is depicted on page 29 of the specification (and the known MMAE sequence).
The elected species does not contain an albumin or fragment as recited in claim 9.
Claim 9 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/7/26.
Claims 1-8 and 10-12 are being examined.
Priority
The priority information is found in the filing receipt of 8/26/24.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/14/24 has been considered by the examiner.
Claim Objections
Claim 8 is objected to because of the following informalities:
Claim 8 does not end in a period.
Appropriate correction is required.
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 1-8 and 10-12 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 refers to the A4 variable as ‘preferably being..’ and also refers to the L’ variable as ‘preferably…’. MPEP 2173.05(d) expressly states that preferences are properly set forth in the specification rather than the claims. Claim 1 is indefinite because it is unclear whether the limitation(s) following the phrase “preferably” are part of the claimed invention. See MPEP § 2173.05(d). None of claims 1-7 and 10-12 fully clarify the claim scope.
Claim 1 recites formula II, but formula II is not legible. For example, the last subscript in the formula is not clear. In similar fashion, formula III of claim 3 is not legible as not all of the subscripts are clear. The formula shown in claim 8 is not legible. For example, determination of whether dashes or lines (compare the Val residue of MMAE) are intended is not clear. Further, the intended bonds in the 5 membered ring with 3 nitrogens is unclear. Thus, none of claims 1-8 and 10-12 are clear.
Claim 4 recites ‘comprised from 1 to 12’. It is unclear if ‘comprised from 1 to 12’ is the same scope as ‘from 1 to 12’ (compare language used in claim 5). Comprising is open ended language and it is unclear if comprising 1 to 12 merely sets a lower limit or if it is an exact range.
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.
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.
Claim(s) 1-8 and 10-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Papot et al. (US 2017/0095525 first cited 6/8/26; ‘Papot’) in view of Slawson et al. (‘Increased N-acetyl-beta-glucosaminidase activity in primary breast carcinomas corresponds to a decrease in N-acetylglucosamine containing proteins’ Biochimica et Biophysica Acta v1537 2001 pages 147-157; ‘Slawson’).
Papot teach conjugated forms of active ingredients (abstract). Papot teach monomethyl auristatin E (MMAE) as an active agent for chemotherapy (sections 0003 and 0024). Papot teach the conjugates as prodrugs in which the active agent is released at the target tissue (section 0006). Papot teach conjugates of a general formula (section 0016 and claim 1) and teach that G is a glucuronyl radical or a derivative thereof (section 0019) where the derivative can include substitution of one or more hydroxyl or carboxylic acid group (section 0083). Papot teach that a specific enzyme is used to activate the drug and suggest cell specificity (sections 0079-0081). Papot teach synthesis of specific compounds (beginning on page 9) and teach the synthesis of a specific compound (page 11 section 0184). Papot teach compositions of the conjugates (claim 11) and teach evaluation on a model of human breast cancer (example 4).
Papot does not recite a compound that reads on claim 1 since Papot teach an example where G is glucuronyl not N-acetylglucosamine.
Slawson teach that N-acetyl-beta-glucosaminidase (O-GlcNAcase) is used to remove N-acetylglucosamine (abstract). Slawson teach that N-acetyl-beta-glucosaminidase activity in breast tumors was investigated (abstract). Slawson teach an increase in N-acetyl-beta-glucosaminidase in breast tumor tissue compared to adjacent tissue (abstract and figure 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Papot because Papot teach conjugates as prodrugs in which the active agent is released at the target tissue (section 0006) and teach conjugates of a general formula (section 0016 and claim 1) and teach that G is a glucuronyl radical or a derivative thereof (section 0019) where the derivative can include substitution of one or more hydroxyl or carboxylic acid group (section 0083). Papot teach that a specific enzyme is used to activate the drug and suggest cell specificity (sections 0079-0081). Since Slawson teach that N-acetyl-beta-glucosaminidase (O-GlcNAcase) is used to remove N-acetylglucosamine (abstract) and teach an increase in N-acetyl-beta-glucosaminidase in breast tumor tissue compared to adjacent tissue (abstract and figure 1) one would have been motivated to substitute N-acetylglucosamine for glucuronyl in the compound of Papot (see page 11). Such substitution involves substitution of one hydroxyl and one carboxylic acid as expressly suggested by Papot (section 0083). Further, Papot teach evaluation on a model of human breast cancer (example 4) and Slawson teach N-acetyl-beta-glucosaminidase activity in breast tumors (abstract). Since Papot teach compositions of the conjugates (claim 11) one would have been motivated to make in such form. One would have had a reasonable expectation of success since Papot teach synthesis of specific compounds (beginning on page 9).
In relation the compound of claims 1-8, when N-acetylglucosamine is substituted for glucuronyl in the compound on page 11 of Papot the resulting structure is such that A is MMAE, Y is NO2, L comprises CH2 (A1), triazole (A2), CH2 (A3), (CH2OCH2)10 (A4), CH2 (A5), NH (A6) and L’ is maleimidocaproyl.
In relation to claims 10-12, Papot teach compositions of the conjugates (claim 11) and teach evaluation on a model of human breast cancer (example 4).
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 1-8 and 10-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10293021 in view of Papot et al. (US 2017/0095525 first cited 6/8/26; ‘Papot’) in view of Slawson et al. (‘Increased N-acetyl-beta-glucosaminidase activity in primary breast carcinomas corresponds to a decrease in N-acetylglucosamine containing proteins’ Biochimica et Biophysica Acta v1537 2001 pages 147-157; ‘Slawson’).
10293021 recites a conjugate of a general form with a G group that comprises glucuronyl or a derivative thereof (claim 1) and recites a more specific conjugate (claim 7). 10293021 recites compositions (claim 11) and methods for treating breast cancer (claims 15-17).
10293021 does not recite a compound that reads on claim 1 since 10293021 teach an example where G is glucuronyl not N-acetylglucosamine.
Papot teach conjugated forms of active ingredients (abstract). Papot teach monomethyl auristatin E (MMAE) as an active agent for chemotherapy (sections 0003 and 0024). Papot teach the conjugates as prodrugs in which the active agent is released at the target tissue (section 0006). Papot teach conjugates of a general formula (section 0016 and claim 1) and teach that G is a glucuronyl radical or a derivative thereof (section 0019) where the derivative can include substitution of one or more hydroxyl or carboxylic acid group (section 0083). Papot teach that a specific enzyme is used to activate the drug and suggest cell specificity (sections 0079-0081). Papot teach synthesis of specific compounds (beginning on page 9) and teach the synthesis of a specific compound (page 11 section 0184). Papot teach compositions of the conjugates (claim 11) and teach evaluation on a model of human breast cancer (example 4).
Slawson teach that N-acetyl-beta-glucosaminidase (O-GlcNAcase) is used to remove N-acetylglucosamine (abstract). Slawson teach that N-acetyl-beta-glucosaminidase activity in breast tumors was investigated (abstract). Slawson teach an increase in N-acetyl-beta-glucosaminidase in breast tumor tissue compared to adjacent tissue (abstract and figure 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 10293021 because Papot teach similar compounds and provides additional details about the G group. Papot teach conjugates as prodrugs in which the active agent is released at the target tissue (section 0006) and teach conjugates of a general formula (section 0016 and claim 1) and teach that G is a glucuronyl radical or a derivative thereof (section 0019) where the derivative can include substitution of one or more hydroxyl or carboxylic acid group (section 0083). Papot teach that a specific enzyme is used to activate the drug and suggest cell specificity (sections 0079-0081). Since Slawson teach that N-acetyl-beta-glucosaminidase (O-GlcNAcase) is used to remove N-acetylglucosamine (abstract) and teach an increase in N-acetyl-beta-glucosaminidase in breast tumor tissue compared to adjacent tissue (abstract and figure 1) one would have been motivated to substitute N-acetylglucosamine for glucuronyl in the compound of Papot (see page 11; or claim 7 of 10293021). Such substitution involves substitution of one hydroxyl and one carboxylic acid as expressly suggested by Papot (section 0083). Further, Papot teach evaluation on a model of human breast cancer (example 4) and Slawson teach N-acetyl-beta-glucosaminidase activity in breast tumors (abstract). Since Papot teach compositions of the conjugates (claim 11) one would have been motivated to make in such form. One would have had a reasonable expectation of success since Papot teach synthesis of specific compounds (beginning on page 9).
In relation the compound of claims 1-8, when N-acetylglucosamine is substituted for glucuronyl in the compound on page 11 of Papot the resulting structure is such that A is MMAE, Y is NO2, L comprises CH2 (A1), triazole (A2), CH2 (A3), (CH2OCH2)10 (A4), CH2 (A5), NH (A6) and L’ is maleimidocaproyl.
In relation to claims 10-12, Papot teach compositions of the conjugates (claim 11) and teach evaluation on a model of human breast cancer (example 4).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
Prosecution Insights