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 8/20/2026 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 and 29 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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/20/2026 has been entered.
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
PNG
media_image1.png
140
500
media_image1.png
Greyscale
wherein M =
PNG
media_image2.png
149
111
media_image2.png
Greyscale
(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 8/20/2026 to the rejection of claims 1, 4, 14, 51, 52, 57, 64, and 65 made by the Examiner under 35 USC 103, double patenting, and/or improper Markush have been fully considered and deemed non-persuasive for the reasons set forth below.
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 is at each occurrence independently a biologically active moiety, an imaging agent, and a radioisotope.
The variable L is at each occurrence independently comprises more than 4 carbon atoms or at least one oxygen atom.
The variable R2 is -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 is -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’ is 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 the claims (see independent claim 1) shares a common structural core and such structural similarity is clearly sufficient to meet the requirement for a proper Markush group. As an example, it is asserted that the variable M is a biologically active moiety, an imaging agent, or a radioisotope binding site, R2 and R3 are independently -OP(=Ra)(Rb)Rc or a linker, L’, R4 is oxygen and R5 is oxo.
EXAMINER’S RESPONSE
All of Applicant arguments were considered, but deem non-persuasive for reasons of record and those set forth below. Independent claim 1 contains the structure,
PNG
media_image3.png
120
200
media_image3.png
Greyscale
which requires one phosphorus atom and two oxygens. The variables R2, 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 bond to a nucleoside. In addition, while Applicant asserts that R4 is oxygen and R5 is oxo, those are substituents off of the main portion of the structure and result in a variable core. Also, it is noted that the claim contains multiple Markush groups and subgroups thereof. Specifically, M is any biologically active moiety, any imaging agent, or any radioisotope binding site; L is optionally any linker provided that at least one occurrence of L comprises more than 4 carbons or at least one occurrence of L comprises oxygen; L1 and L2 are independently absent or any alkylene linker; R1 is H, alkyl, or alkoxy; R2 and R3 are independently L’ or OP(=Ra)(Rb)Rc; R4 is oxygen; R5 is oxo; Ra = oxygen or sulfur; Rb is OH, SH, O, S, ORd, or SRd; Rc is OH, SH, O, S, ORd, OL’, SRd, OdT, alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether, or thiophosphoalkylether; Rd is any counter ion; L’ is any targeting moiety, any linker comprising a covalent bond to a targeting moiety, any linker comprising a covalent bond to a solid support, or any linker comprising a covalent bond to a nucleoside; and n is an integer of one or greater. The compounds embrace species from various different chemical classes as they include structurally distinct compounds that are non-obvious variants of one another. 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
PNG
media_image4.png
122
200
media_image4.png
Greyscale
. Specifically, the structure in the copending application,
PNG
media_image5.png
159
154
media_image5.png
Greyscale
wherein L2 is
PNG
media_image6.png
65
146
media_image6.png
Greyscale
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
PNG
media_image6.png
65
146
media_image6.png
Greyscale
; 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 Examiner must show that the invention recited in the claims under examination are patentably indistinct variation of the invention recited in the claims of the reference patent or application. In addition, it is asserted that the definition of M in the pending claim is patentably distinct and does not overlap with or encompass any of the compounds recited in the cited copending applications and patents.
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 variables in the document include any biological moiety. The pending claims allow the variable M to be any biologically active moiety, any imaging agent, and any radioisotope binding sited. 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
PNG
media_image4.png
122
200
media_image4.png
Greyscale
. 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
PNG
media_image4.png
122
200
media_image4.png
Greyscale
. 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
PNG
media_image4.png
122
200
media_image4.png
Greyscale
. 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
PNG
media_image4.png
122
200
media_image4.png
Greyscale
. 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
PNG
media_image7.png
121
200
media_image7.png
Greyscale
wherein the variables have the definitions set forth therein.
Claim 4 is directed to a compound of formula
PNG
media_image8.png
120
201
media_image8.png
Greyscale
wherein the variables have the definitions set forth therein.
Matray discloses the species
PNG
media_image9.png
214
265
media_image9.png
Greyscale
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 =
PNG
media_image10.png
141
173
media_image10.png
Greyscale
. Thus, the limitation of claims 1 and 4 are met.
PNG
media_image11.png
491
454
media_image11.png
Greyscale
APPLICANT’S ASSERTIONS
In summary, it is asserted that the invention is distinguished over the cited prior art because independent claim 1 was amended to exclude ‘fluorescent dye’ and as such M is a biologically active moiety, and imaging agent, or a radioisotope binding site. In addition, it is asserted that the radioactive isotopes (e.g., 18F, 32P, and 125I) of Matray et al are not biologically active moieties, imaging agents, or radioisotope binding sites. Still, it is asserted that hindsight was used in order to establish the rejection.
EXAMINER’S RESPONSE
Applicant’s arguments were considered, but deemed non-persuasive for reasons of record and those set forth herein. Specifically, Applicant does not establish boundaries in the disclosure as to how one is defining biologically active moieties, imaging agents, and radioisotope binding sites. Thus, the term are given the broadest reasonable interpretation. While Applicant has removed ‘fluorescent’ from independent claim 1, the term ‘imaging agent’ given the broadest reasonable interpretation includes fluorescent agents. As support of the Examiner’s position, Gosee et al (Coordination Chemistry Reviews, 2025, Vol. 532, No. 216523, pages 1-21) is made of record. Gosee et al is directed to imaging modalities. The imaging modalities include, for example, CT, MRI, ultrasound, SPECT, PET and fluorescence imaging see entire documents, especially, abstract; and page 6, Section 2.2.2, ‘Optical Imaging’, left and right columns, bridging paragraph). Thus, fluorescence as well as other imaging modalities would be considered as imaging agent as well. As a result, the pending claims still read on the cited prior art.
In addition, it is duly noted that while Applicant has deleted ‘fluorescent dye’ from independent claim 1, claim 64 which depends upon independent claim 1 contains a fluorescent dye (see the definition of the variable F in claim 64). Thus, the skilled artisan would recognize that the phrase ‘imaging agent’ encompasses fluorescent dyes as well.
In regard to Applicant’s assertion about the radioactive isotopes 18F, 32P, and 125I, the following response is given. Matray et al, page 17, lines 16-22, (see excerpt below), render obvious radioactive binding compounds. Specifically, Matray et al disclose that embodiments may be isotopically labelled with isotopes such as 2H, 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, 31P, 32P, 35S, 18F, 36Cl, 123I, and 125I. The compounds may be used for determining the presence of dead cells in a sample. The method comprises contacting a sample with a compound, allowing the compound to bind or associate with the dead cells, and observing a signal for the compound bound or associated with the dead cells (page 71, claim 50). Thus, it would be obvious to one of ordinary skill in the art prior to the effective filing date of the pending invention that the invention of Matray et al includes radioisotopes conjugated to compounds which bind/associate to cells. As a result, those substances would be classified as substances targeting abilities.
Matray et al (WO 2017/197144), page 17, lines 16-22
PNG
media_image12.png
168
485
media_image12.png
Greyscale
It is noted that in the disclosure Applicant does not set forth conditions that exclude any particular radioisotope binding compounds. In addition, like Matray et al (WO 2017/197144), Applicant’s specification (page 16, lines 15-21) discloses that the compounds may be isotopically labeled such that one or more atoms is replace by an atom having a different atomic mass or mass number. Possible isotopes that may be incorporated include 2H, 3H, 11C, 13C, 14C, 13N, 15N, 15O, 17O, 18O, 31P, 32P, 35S, 18F, 36Cl, 123I, and 125I.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
For the reasons set forth supra, the 103 rejection is still deemed proper.
NEW GROUNDS OF REJECTIONS
112 Second Paragraph Rejections
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, 4, 14, 51, 52, 57, 64, and 65 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.
Claims 1, 4, 14, 51, 52, 57, 64, and 65: Independent claim 1 is ambiguous because for the following reasons. According to MPEP 2173.05(h), while a Markush grouping may include a large number of alternatives, and not necessarily be indefinite under 35 USC 112(b), in certain circumstances, a Markush group may be so expansive that a skilled artisan cannot determine the metes and bounds of the claimed invention. In the pending claims, the invention is directed compounds of formula
PNG
media_image13.png
165
273
media_image13.png
Greyscale
wherein M is any biologically active moiety, imaging agent, or radioisotope binding site; L is optionally any linker provided that at least one occurrence of L comprises more than 4 carbons or at least one occurrence of L comprises oxygen; L1 and L2 are independently absent or any alkylene linker; R1 is H, alkyl, or alkoxy; R2 and R3 are independently L’ or OP(=Ra)(Rb)Rc; R4 is oxygen; R5 is oxo; Ra = oxygen or sulfur; Rb is OH, SH, O, S, ORd, or SRd; Rc is OH, SH, O, S, ORd, OL’, SRd, OdT, alkyl, alkoxy, heteroalkyl, heteroalkoxy, alkylether, alkoxyalkylether, phosphate, thiophosphate, phosphoalkyl, thiophosphoalkyl, phosphoalkylether, or thiophosphoalkylether; Rd is any counter ion; L’ is any targeting moiety, any linker comprising a covalent bond to a targeting moiety, any linker comprising a covalent bond to a solid support, or any linker comprising a covalent bond to a nucleoside; and n is an integer of one or greater.
Thus, the pending claims encompasses compounds defined by multiple Markush groups and subgroups thereof. As a result, pending claim 1 encompasses a massive number of distinct alternative members such that one skilled in the art cannot determine the metes and bounds of the claim. Hence, due to an inability to envision all of the compounds defined by the Markush groups, the claim is deemed to be vague and indefinite.
Claim 64: The claim is ambiguous because it contains subject matter that is outside the scope of independent claim 1. Specifically, independent claim 1 was amended to exclude references to M being a fluorescent dye; however, disclose that F is a fluorescence dye which is found the last three structures in claim 64. In addition, for the variable R3, dT was deleted as a possible option (se claim 1, line 14). All of the structures appearing in claim 64 contain dT
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 5/31/2026 was considered.
Comments/Notes
In claim 1, lines 10-11, it is not necessary to use both ‘optional and absent’. The use of the phrase ‘optional alkylene linker’ indicates that the alkylene linker may or may not be present.
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.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
October 7, 2026
Prosecution Insights