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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 9/23/2025 wherein claims 2, 3, 5-8, 12, 13, 15-21, 23-27, 30, 32-44, 46, 48, 49, 53-56, 58-63, and 67-83 were canceled and claims 1, 4, 14, 51, 52, 57, and 64 were amended.
Note(s): Claims 1, 4, 9-11, 14, 22, 28, 29, 31, 45, 47, 50-52, 57, 64-66, and 84 are pending.
Priority
This application is a 371 of PCT/US2020/027750 filed 4/10/2020;
PCT/US2020/027750 claims benefit to PRO 62/877,144 filed 7/22/2019; and PCT/US2020/027750 claims benefit to PRO 62/832,723 filed 4/11/2019.
Note(s): The earliest effective filing date is 4/11/2019 as the pending invention is fully supported in provisional application 62/832,723.
Applicant’s Election
Once again, Applicant’s election without traverse of Group I (pending claims 1, 4, 9-11, 14, 22, 28, 29, 31, 45, 47, 50-52, 57, 64, and 65) in the reply filed on 4/4/2025 is acknowledged. The restriction was deemed proper and made FINAL.
Applicant elected the species
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wherein M =
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(monomethyl auristatin E). Pending claims 1, 4, 14, 51, 52, 57, 64, and 65 read on the elected species.
Applicant’s elected species was searched and no prior art was found which could be used to reject the claims. Thus, the search was expanded to the species cited in the 103 rejection below. The search was not further extended because prior art was found which could be used to reject the claims.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 9/23/2025 to the rejection of claims 1, 4, 14, 51, 52, 57, 64, and 65 made by the Examiner under 35 USC 103, 112, double patenting, and/or improper Markush have been fully considered and deemed persuasive-in-part for the reasons set forth below.
Written Description Rejection
The 112 first paragraph (written description) rejection is WITHDRAWN because Applicant amended the claims to overcome the rejection.
112 Second Paragraph Rejections
All outstanding 112 second paragraph rejections are WITHDRAWN because Applicant amended the claims to overcome the rejections.
Improper Markush Rejection
Claims 1, 4, 14, 51, 52, 57, 64, and 65 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings present in variables M, L, R2, R3, and L’ are as set forth below.
The variable M may be at each occurrence independently a biologically active moiety, a fluorescent dye, an imaging agent, and a radioisotope.
The variable L may be at each occurrence independently comprises more than 4 carbon atoms or at least one oxygen atom.
The variable R2 may be absent, hydrogen, OH, SH, alkyl, alkoxy, alkylether, heteroalkyl, dT, -OP(=Ra)(Rb)Rc, or a linker, L’, selected from a targeting moiety, a linker comprising a covalent bond to a targeting moiety, a linker comprising a covalent bond to a solid support, a linker comprising a covalent bond to a solid support residue, or a linker comprising a covalent bond to a nucleoside.
The variable R3 may be absent, hydrogen, OH, SH, alkyl, alkoxy, alkylether, heteroalkyl, dT, -OP(=Ra)(Rb)Rc, or a linker, L’, selected from a targeting moiety, a linker comprising a covalent bond to a targeting moiety, a linker comprising a covalent bond to a solid support, a linker comprising a covalent bond to a solid support residue, a linker comprising a covalent bond to a nucleoside.
The variable L’ may be at each occurrence independently a targeting moiety, a linker comprising a covalent bond to a targeting moiety, a linker comprising a covalent bond to a solid support, a linker comprising a covalent bond to a solid support residue, or a linker comprising a covalent bond to a nucleoside.
The Markush groupings are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use because they the species of each respective grouping does not contain a common core but comprise a wide variety of distinct substances and rings optionally containing one or more heteroatom and carbon atom combinations (linear/branched as well as substituted and unsubstituted all of which are optionally substituted with a heteroatom) that may be linked in various orientations with halogens, nitro, or reactive groups, for example. Thus, there is no common core consistent with the respective variable grouping since the claims embrace species from a multitude of different chemical classes and subclasses.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
APPLICANT’S ASSERTIONS
In summary, it is asserted that asserted that essentially the presence of the phrase ‘at least one occurrence of M is not a fluorescent dye’ in combination with R2 and R3 and M being a biologically active moiety a fluorescent dye, an imaging agent, or a radioisotope binding site are sufficient to address the improper Markush rejection issue.
EXAMINER’S RESPONSE
All of Applicant arguments were considered, but deem non-persuasive for reasons of record and those set forth below. In independent claim 1, the only required components in structure I,
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, is one phosphorus atom and two oxygens. The variables R2, R5, R4, M, L, L1, R1, L2, and R3 all vary in the structure ranging in some instances from a hydrogen atom to species comprising a covalent bon to a nucleoside. Thus, there is no common core consistent with compounds since the claims embrace species from various different chemical classes. Thus, the rejection is still deemed proper.
Double Patenting Rejections
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.
(I). Claims 1 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/570,283 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to compounds encompassed by
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. Specifically, the structure in the copending application,
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wherein L2 is
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and the variables of the present invention are defined as follows: R2 (pending application) = R1 (copending application); R1 (pending invention) = hydrogen; x5 (copending application) = 1; L1 (pending application) = alkyl portion of
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; L (pending application) = L1 (copending application); M (copending application, fluorescent dye) = M (copending application, cyanine dye); L2 (pending application) = L3 (copending application) = SH; and R3 (pending application) = R2 (copending application) = SH. Thus, the application disclose overlapping subject matter.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
APPLICANT’S ASSERTIONS
In summary, it is asserted that the variable M recited in the amended claim does not meet any of the compounds recited in the double patenting document.
EXAMINER’S RESPONSE
Applicant’s arguments were considered, but deemed non-persuasive for reasons of record and those set forth herein. In particular, the various M is any biological moiety. There is no limit or definition present in the claims to limit how a biologically active moiety is to be limited. As a result, of the moieties being used to evaluate a biological system, the compounds of the pending invention, including the variable M, would be a biologically active moiety. Hence, the rejection is still deemed proper.
(II). Claims 1, 4, and 65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 17 of U.S. Patent No. 10,954,391. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to compounds encompassed by
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. The definitions of R2, R4, R5, R1, n, and R3 overlap. L1 corresponds to patented L7. M corresponds to patented M1. L corresponds to patented L1. L2 corresponds to patented L3. Thus, the inventions disclose overlapping subject matter.
APPLICANT’S ASSERTIONS
In summary, it is asserted that the variable M recited in the amended claim does not meet any of the compounds recited in the double patenting document.
EXAMINER’S RESPONSE
Applicant’s arguments were considered, but deemed non-persuasive for reasons of record and those set forth herein. In particular, the various M is any biological moiety. There is no limit or definition present in the claims to limit how a biologically active moiety is to be limited. As a result, of the moieties being used to evaluate a biological system, the compounds of the pending invention, including the variable M, would be a biologically active moiety. Hence, the rejection is still deemed proper.
(III). Claims 1, 4, and 65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 15, and 20 of U.S. Patent No. 11,434,374. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to compounds encompassed by
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. The definitions of R2, R4, R5, R1, n, and R3 overlap. L1 corresponds to patented L7. M corresponds to patented M1. L corresponds to patented L1. L2 corresponds to patented L3. Thus, the inventions disclose overlapping subject matter.
APPLICANT’S ASSERTIONS
In summary, it is asserted that the variable M recited in the amended claim does not meet any of the compounds recited in the double patenting document.
EXAMINER’S RESPONSE
Applicant’s arguments were considered, but deemed non-persuasive for reasons of record and those set forth herein. In particular, the various M is any biological moiety. There is no limit or definition present in the claims to limit how a biologically active moiety is to be limited. As a result, of the moieties being used to evaluate a biological system, the compounds of the pending invention, including the variable M, would be a biologically active moiety. Hence, the rejection is still deemed proper.
(IV). Claims 1, 4, and 65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8, 9, and 13 of U.S. Patent No. 11,827,661. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to compounds encompassed by
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. The definitions of R2, R4, R5, R1, n, and R3 overlap. L1 corresponds to patented L7. M corresponds to patented M1. L corresponds to patented L1. L2 corresponds to patented L3. Thus, the inventions disclose overlapping subject matter.
APPLICANT’S ASSERTIONS
In summary, it is asserted that the variable M recited in the amended claim does not meet any of the compounds recited in the double patenting document.
EXAMINER’S RESPONSE
Applicant’s arguments were considered, but deemed non-persuasive for reasons of record and those set forth herein. In particular, the various M is any biological moiety. There is no limit or definition present in the claims to limit how a biologically active moiety is to be limited. As a result, of the moieties being used to evaluate a biological system, the compounds of the pending invention, including the variable M, would be a biologically active moiety. Hence, the rejection is still deemed proper.
(V). Claims 1, 4, and 65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10-12, and 17 of U.S. Patent No. 11,685,835. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to compounds encompassed by
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. The definitions of R2, R4, R5, R1, n, and R3 overlap. Patented m1, x, and y are all zero. Patented z is one. L1 corresponds to patented L3. M corresponds to patented M. L corresponds to patented L1. L2 corresponds to patented L2. Thus, the inventions disclose overlapping subject matter.
APPLICANT’S ASSERTIONS
In summary, it is asserted that the variable M recited in the amended claim does not meet any of the compounds recited in the double patenting document.
EXAMINER’S RESPONSE
Applicant’s arguments were considered, but deemed non-persuasive for reasons of record and those set forth herein. In particular, the various M is any biological moiety. There is no limit or definition present in the claims to limit how a biologically active moiety is to be limited. As a result, of the moieties being used to evaluate a biological system, the compounds of the pending invention, including the variable M, would be a biologically active moiety. Hence, the rejection is still deemed proper.
103 Rejection
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.
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.
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Matray (WO 2017/197144).
Independent claim 1 is directed to a compound of formula
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wherein the variables have the definitions set forth therein.
Claim 4 is directed to a compound of formula
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wherein the variables have the definitions set forth therein.
Matray discloses the species
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on page 52, line 3. The compound encompasses the formula above at the following conditions: R1 = hydrogen; R3 = hydrogen; L2 = absent; R4 = (NR6)2 wherein R6 = alkyl (substituted alkyl, see specification, page 5, lines 15-16); R2 = CH2-CH2-CN (alky (substituted alkyl), see specification, page 5, lines 15-16) L = absent; L1 = CH2-CH2-CH2-CH2-CH2 (alkyl); and M =
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. Thus, the limitation of claims 1 and 4 are met.
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APPLICANT’S ASSERTIONS
In summary, it is asserted that the invention is distinguished over the cited prior art because when n = 1, there is only one M group and claim 1 has the proviso that at least one occurrence of M is not a fluorescent dye. In addition, it is asserted that the M of Matray et al does not comprise a biologically active moiety, an imaging agent, or radioisotope binding site as required for claim 1.
EXAMINER’S RESPONSE
Applicant’s arguments were considered, but deemed non-persuasive for reasons of record and those set forth herein. Specifically, in regards to Applicant’s assertions that there is only one M when n = 1 and the proviso that at least one occurrence of the variable M is not a fluorescent dye, the proviso is not applicable at n = 1. The proviso is applicable when n = 2 or more. It is at those conditions that at least one of the M values must be other than a fluorescent dye (e.g., an imaging agent, a radioisotope binding site, or a biologically active moiety). When n = 1, there is no proviso and as a result, one may have a fluorescent dye present.
In regards to the assertion that that the variable M of Matray et al does not comprise a biologically active moiety, and imaging agent, or radioisotope binding site, the components of the composition of Matray et al are used to generation compounds useful as fluorescent or colored dyes that enable the detection of analyte molecules such as biomolecules (page 2, lines 7-18). As a result, it would have been obvious to the skilled artisan that the components of the composition used for evaluating biomolecules is biocompatible. Hence, the variable M like the other components would be a biological component (a biologically actively moiety).
Also, it is noted that while the proviso is directed to a fluorescent dye, Matray et al disclose that the structure may include radioisotopes such as 18F (a fluorescent isotope) as well as 32P and 125I which are both radioactive isotopes, not a fluorescent isotopes (page 17, lines 16-22). Thus, the scope of Matray et al is not limited to fluorescent molecules.
For the reasons set forth herein, the rejection is still deemed proper.
Withdrawn Claims
Claims 9-11, 22, 28, 29, 31, 45, 47, 50, 66, and 84 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention/species.
Information Disclosure Statement
The information disclosure statement filed 9/30/2025 was considered.
Comments/Notes
It should be noted that the full scope of Group I was not searched.
Conclusion
Claims 1, 4, 14, 51, 52, 57, 64, and 65 are rejected and claims 9-11, 22, 28, 29, 31, 45, 47, 50, 66, and 84 are withdrawn.
THIS ACTION IS MADE FINAL. 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.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G. Hartley can be reached at (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
April 15, 2026
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