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 .
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 01/05/2026 has been considered.
Claim Status
The claim set and Applicant’s remarks filed January 05, 2026 have been entered. Claims 7-9 have been canceled. Thus, claims 1-6 and 10-22 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on September 04, 2025:
(I) The objection to the drawings is withdrawn in view of Applicant’s amendment to the drawings filed January 05, 2026.
(II) The objection to claims 1 and 21-22 is withdrawn in view of Applicant’s amendments to claims 1 and 21-22.
(III) The rejection of claims 1-22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendments to claims 1, 12 and 22, respectively.
(IV) The rejection of claims 7-9 and 11 under 35 U.S.C. 102((a)(1) or (a)(2)) or, in the alternative, under 35 U.S.C. 103 over Brundo et al.; and
(V) The provisional rejection of claims 7-9 and 11 on the ground of nonstatutory double patenting are withdrawn in view of Applicant’s cancellation of claims 7-9 as discussed above and in view of amendments to claim 1, specifically “a compound consisting of Formula I”, wherein claim 11 recites that L1 is absent.
Claim Interpretation
Independent claims 1 and 22 each recite the limitation “L1 represents a linking group”, see claim 1, line 12 and claim 22, line 12. The Examiner also respectfully notes claim 1 and claim 22 each recite Formula (I), wherein Formula (I) represents X-L1-A, see claim 1, line 6 and claim 22, line 6.
The Examiner also respectfully notes L1 is recited as a limitation defined by its function, e.g. L1 is a structure that links the tissue binding moiety (e.g. X) to the active agent (e.g. A) within Formula (I) as recited in both claim 1 and claim 22.
Consequently, the Examiner reasonably interprets any structure linking the tissue binding moiety (e.g. X) to the active agent (e.g. A) is encompassed by the scope of the phrase “a linking group”.
The Examiner further respectfully notes Applicant’s specification does not explicitly define the phrase “linking group” within the disclosure, but does exemplify “the linking group” on pp. 19-21.
However, the Examiner respectfully notes exemplification is not an explicit definition, especially in view of the specification stating “when present, the linking group can be any suitable group or moiety which is at minimum bivalent, and connects the two radical moieties to which the linking group is attached in the compounds described herein” (pg. 19, linking groups, paragraph 1).
The Examiner respectfully notes the two radical moieties to which the linking group is attached are the tissue binding moiety (e.g. X) and the active agent (e.g. A) as recited within Formula (I) of claim 1 and claim 22.
Accordingly, the Examiner reasonably interprets in view of the disclosures of the specification and the recitations of independent claim 1 and claim 22, the limitation “L1” as recited within Formula (I) of claim 1 and claim 22 is any structure linking the tissue binding moiety (e.g. X) to the active agent (e.g. A).
Thus, in view of the recitations of independent claims 1 and 22, and in view of the specification as a whole, the Examiner reasonably interprets that if any structure links the tissue binding moiety to the active agent as discussed above it will read on Formula (I) of both claim 1 and claim 22.
Response to Arguments
(I) The rejection of claims 1-6, 10 and 13-22 under 35 U.S.C. 102((a)(1) or (a)(2));
(II) The rejection of claim 12 under 35 U.S.C. 103.; and
(III) The provisional rejection of claims 1-10, 12-16 and 17-22 on the ground of nonstatutory double patenting are maintained.
Applicant argues:
(A) Amendments to both claim 1 and claim 22 recite “a compound consisting of Formula (I)”, see Applicant’s remarks, pg. 8, paragraph 1.
(B) Independent claims 1 and 22 have been amended to exclude the “Click Target” and “Click Prodrug” components disclosed within Brundo, and thus are novel over Brundo, see Applicant’s remarks, pg. 8, paragraph 2.
(C) Applicant asserts Brundo fails to teach, suggest or render obvious the subject matter of currently amended claim 1 and thus claim 12 is novel and non-obvious for the reasons independent claim 1 has been shown novel and non-obvious as discussed above, see Applicant’s remarks, pg. 8-9, 35 USC § 103 – Obviousness, paragraph 1.
(D) Applicant respectfully submits when comparing the reference claims of copending application ‘025 with the instant claims of the instant application with regard to the provisional double patenting rejection indicates that the scope of these claims are distinct and separate inventions as claimed, see Applicant’s remarks, pg. 9, Double Patenting, paragraph 1.
With respect to Applicant’s arguments (A)-(C), the Examiner respectfully reiterates the Examiner’s interpretation of the limitation “a linking group” as recited in independent claim 1, line 12 and claim 22, line 12 as discussed in greater detail above and with respect to formula (I) recited as “X-L1-A” within amended independent claim 1 and claim 22.
Additionally, the Examiner respectfully reiterates the Examiner’s reasonable interpretation that “L1” as recited within Formula (I) of claim 1 and claim 22 is any structure linking the tissue binding moiety (X) to the active agent (A).
The Examiner respectfully notes Brundo teaches delivering an active agent to a target tissue of a subject comprising contacting the target tissue with a click target defined by Formula I, which is depicted as X-L1-CM1; and contacting the target tissue with a click prodrug defined by Formula II, A-L2-CM2.
The Examiner also respectfully notes Brundo teaches the first click motif and the second click motif are selected such that the first click motif is capable of chemically reacting with the second click motif to form a covalent bond.
Therefore, the resulting structure taught by Brundo which delivers the active agent to the target tissue when Formula (I) and Formula (II) of Brundo are connected via a covalent bond as discussed above is depicted as X-L1-CM1-CM2-L2-A; or when L1 and L2 are absent as taught by Brundo, results in the structure known as X-CM1-CM2-A.
Thus, the Examiner respectfully notes the teachings of Brundo still anticipate or make obvious the maintained rejected claims as discussed above; as the structure of Brundo anticipates Formula (I) as recited within independent claim 1 and claim 22 because the teachings of Brundo further specify the structure linking the tissue binding moiety (e.g. X) as taught by Brundo to the active agent (e.g. A) also taught by Brundo; as the Examiner reasonably interprets the structure of either “-L1-CM1-CM2-L2-“ or “-CM1-CM2-“ as taught by Brundo above anticipates the recitation of “L1” as recited within Formula (I) of independent claim 1 and claim 22 as reasonably interpreted by the Examiner as discussed in greater detail above.
With respect to Applicant’s argument (D), the Examiner respectfully notes the copending application ‘025 has been amended in view of the claim set filed January 7, 2026. The Examiner also respectfully notes the double patenting rejections below have been modified in view of these amendments discussed above.
The Examiner respectfully notes the ‘025 application still recites the structure “X-L1-CM1-CM2-L2-A” within its recited methods of reference claim 1 and claim 27.
Moreover, the Examiner also respectfully notes the recitations of copending application ‘025 still anticipate or make obvious the maintained provisionally rejected claims as discussed above; as copending application ‘025 anticipates Formula (I) as recited within instant claim 1 and instant claim 22 because the recitations of ‘025 further specify the structure linking the tissue binding moiety (e.g. X) as recited by ‘025 to the active agent (e.g. A) also recited by ‘025; as the Examiner reasonably interpreted the recitation of “L1” as recited within Formula (I) of instant claim 1 and instant claim 22 as discussed in greater detail above.
Thus, Applicant’s arguments (A)-(D) have been fully considered but are not found persuasive.
New Claim Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on January 05, 2026, where the limitations in pending claims 1-6 and 10-22 as amended now have been changed. Therefore, rejections from the previous Office Action, dated January 05, 2025, have been modified and are listed below.
35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 10 and 13-22 are rejected under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by Brundo et al. (Published 02 April 2020, Filed 30 September 2019, WO-2020069488-A1, IDS filed 04/14/2023).
Regarding claims 1-6, 10 and 13-22, Brundo teaches delivering an active agent to a target tissue of a subject, comprising contacting the target tissue with a click target defined by Formula I, which is depicted as X-L1-CM1, wherein X represents a tissue binding moiety; L1 is absent or represents a linking group; and CM1 represents a first click motif, see pg. 1, lines 18-23; and
contacting the target tissue with a click prodrug defined by Formula II, A-L2-CM2, wherein A represents an active agent, L2 is absent or represents a linking group; and CM2 represents a second click motif complementary to the first click motif, see pg. 1, lines 23-28.
Brundo teaches the first click motif and the second click motif are selected such that the first click motif is capable of chemically reacting with the second click motif to form a covalent bond (e.g. wherein A represents an active agent, required in claim 1, line 10), see pg. 2, lines 6-8.
Brundo teaches the click target can include any suitable tissue binding moiety, and the tissue binding moiety can be any moiety which functions to anchor the click target to the target tissue (e.g. the tissue binding moiety comprises a functional group capable of chemically reacting with the target tissue to form a covalent bond, required in claim 1, lines 11-12);
wherein the tissue binding moiety comprises a functional group capable of chemically reacting with an amine group in a peptide (e.g. an extracellular matrix protein) to form a covalent bond, such as a hydroxysuccinimidyl (NHS) group or a sulfo-hydroxysuccinimidyl (sNHS) group (e.g. the tissue binding moiety required in claim 4), see pg. 20, lines 12-15;
or the tissue binding moiety comprises a functional group capable of chemically reacting with a thiol group in a peptide to form a covalent bond, such as a maleimide group (e.g. the tissue binding moiety, required in claim 6), see pg. 20, lines 18-20.
Brundo teaches L1 is absent; and L1 is present, see pg. 2, lines 12-14.
Brundo teaches the active agent can comprise a diagnostic agent (e.g. required in claim 13) or a can comprise a therapeutic agent (e.g. required in claim 13), see pg. 2 lines 15-16.
Brundo teaches the therapeutic agent can comprise an anti-cancer drug (e.g. required in claim 16); a drug that promotes wound healing (e.g. required in claim 17); a drug that promotes vascularization or a drug that prevents restenosis (e.g. required in claim 18); and a drug that treats or prevents infection (e.g. required in claim 19), see pg. 2, lines 16-20.
Brundo teaches the target tissue can comprise a solid tumor (e.g. required in claim 20), see pg. 18, line 12.
Brundo teaches contacting the target tissue with a click target comprises injecting a pharmaceutical composition comprising the click target into the target tissue (e.g. injecting required in claim 21), see pg.2, line 21-23.
With respect to claim 22, Brundo teaches maintaining or reducing the size of a tumor in a subject in need thereof, comprising injecting into the tumor a click target defined by Formula I, which is depicted as X-L1-CM1, wherein X represents a tissue binding moiety; L1 is absent or represents a linking group; and CM1 represents a first click motif, see pg. 1, lines 18-23; and administering to the subject a click prodrug defined by Formula II, A-L2-CM2, wherein A represents an active agent, L2 is absent or represents a linking group; and CM2 represents a second click motif complementary to the first click motif, thereby maintaining or reducing the size of the tumor in the subject, see pg. 18, line 22 – pg. 19, line 2.
Brundo teaches the first click motif and the second click motif are selected such that the first click motif is capable of chemically reacting with the second click motif to form a covalent bond (e.g. wherein A represents an active agent, required in claim 22, line 10), see pg. 19, line 30 – pg. 20, line 1.
Brundo teaches an example click target (also referred to as a small molecule depot) incorporates an N-hydroxysuccinimide (NHS) ester which can rapidly form covalent bonds with primary amines. Notably sulfo-NHS can be readily soluble in water; and to create a depot that can be injected into the body, an ester was used that takes advantage of the presence of upregulated collagen expression in fibrous tumors, such as a pancreatic cancer; wherein the extracellular matrix includes collagen, see pg. 42, lines 5-11.
Brundo teaches a sulfo-NHS ester conjugate binds to the extracellular matrix of tumors, and the ester’s reaction with the extracellular matrix amines anchors the click motifs inside the tumor to act as a local depot to capture and release active drug over weeks at a time, see pg. 42, lines 20-22.
The Examiner reasonably interprets the sulfo-NHS that is exemplified in Formula I as discussed above is capable of binding to collagen as required in claim 10, as Brundo teaches a sulfo-NHS ester conjugate binds to the extracellular matrix of tumors, wherein the extracellular matrix includes collagen as discussed above; and thus meets the limitation wherein the tissue binding moiety comprises a functional group capable of chemically reacting with tissue to form a covalent bond, as required in claim 22, lines 12-13.
Although, Brundo does not explicitly teach “a therapeutically effective amount of a compound defined by Formula I” as required in claim 1, line 3, and claim 22, line 3, however the Examiner respectfully notes that Brundo teaches the active agent is administered to a patient for the treatment, prevention or diagnosis of a disease or disorder, see pg. 28, lines 7-10.
Therefore, the Examiner reasonably interprets that when the click target contains an anti-cancer drug as discussed above, for the maintaining or reducing the size of a tumor as discussed above, for example a pancreatic tumor as discussed above, the Examiner reasonably interprets the amount injected as discussed above is a “therapeutically effective amount” to treat the disease or disorder, in this case in maintaining or reducing the size of the tumor as discussed above. Thus, the limitation of “a therapeutically effective amount of a compound defined by Formula I” as required in claim 1, line 3, and claim 22, line 3 is met by the teachings of Brundo.
Thus, based on the teachings of Brundo as discussed above, Brundo anticipates claims 1-6, 10 and 13-22
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.
(I) Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Brundo et al. (Published 02 April 2020, Filed 30 September 2019, WO-2020069488-A1, IDS filed 04/14/2023) as applied to claims 1-6, 10 and 13-22 above, and further in view of Ezrin et al. (Published 30 September 1999, WO-9948536-A2, PTO-892).
Brundo addresses claims 1-6, 10 and 13-22 as written above. Although, Brundo does not teach wherein L1 is absent as required in claim 11.
However, in the same field of endeavor of delivering active agents, Ezrin teaches methods and compositions for localized delivery of therapeutic agents which are capable of forming covalent bonds with a site of interest, where therapeutic agents include anti-cancer agents, see abstract.
Ezrin teaches a local delivery agent comprising a compound of the formula X-Y-Z, wherein X is selected from the group consisting of and including anti-cancer agents; Y is a linking group consisting of 0-30 atoms (when Y is 0 atoms, the Examiner respectfully notes this teaching corresponds to when L1 is absent as required in claim 11); and Z is a chemically reactive entity capable of reaction with a reactive functionality on fixed blood components to form covalent bonds therewith, see pg. 6, lines 4-12.
Ezrin teaches Z may be selected from and including N-hydroxy sulfosuccinimide and maleimide-benzoyl-succinimide, see pg. 6, lines 10-15.
Ezrin defines fixed blood components to include tissues, interstitial proteins, fibrin proteins and collagens, see pg. 8, lines 15-20.
It would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have substituted the active agent comprising the “Click Target” and “Click Prodrug” as taught by Brundo above for the local delivery agent as taught by Ezrin above as a simple substitution of one known element for another for delivering an active agent to a tissue. One of ordinary skill in the art would have been motivated to make said substitution in order to deliver the active agent to the target tissue of the subject of Brundo as discussed above.
One of ordinary skill in the art would have had a reasonable expectation of success to have made said substitution as discussed above because both Brundo and Ezrin are drawn to delivering an active agent to a tissue; where said agent comprises delivering a compound comprising a therapeutic agent and a chemically reactive entity; wherein said reactive entity contains either N-hydroxy sulfosuccinimide or maleimide; and wherein said reactive entity is capable of forming covalent bonds with a site of interest; wherein said site of interest includes tissues and collagens as discussed above.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have substituted the agent of Brundo for the agent of Ezrin as within the scope of the artisan as combining prior art elements according to known compounds and methods to yield predictable results. One of ordinary skill in the art would have been motivated to make said substitution because both the agents of Brundo and the agents of Ezrin are used for the same intended purpose of delivering a therapeutic agent as discussed above.
One of ordinary skill in the art would have had a reasonable expectation of success to have made the substitution as discussed above, because Ezrin teaches local delivery agents comprising a tissue binding moiety and a therapeutic agent which may or may not be linked via a linking group, and particularly wherein said tissue binding moiety is N-hydroxy sulfosuccinimide as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Brundo et al. (Published 02 April 2020, Filed 30 September 2019, WO-2020069488-A1, IDS filed 04/14/2023).
Brundo addresses claim 1 as written above. Although, Brundo does not explicitly teach wherein L1 represents a cleavable linker selected from the group consisting of a hydrolytically cleavable linker, a photo cleavable linker, and an enzymatically cleavable linker, required in claim 12.
However, Brundo further teaches when L2 represents a linking group, L2 is a cleavable linker (e.g. a hydrolysable, an enzymatically cleavable linker, and a photocleavable linker, required in claim 12), see pg. 2, lines 12-14. The Examiner respectfully notes L2 is a linker within the click prodrug of Formula II that links the active agent (e.g. A) within the click prodrug of Formula (II) to the tissue binding moiety (e.g. X) within the click target of Formula (I).
Additionally, the Examiner respectfully reiterates their interpretation if any structure links the tissue binding moiety to the active agent it will correspond to L1 as discussed in the Claim Interpretation section above, and since the structure of “-L1-CM1-CM2-L2-“ as taught by Brundo above which links the tissue binding moiety (e.g. X) to the active agent (e.g. A) as discussed above comprises L2 exemplified as a cleavable linker which is a hydrolysable, an enzymatically cleavable, or a photocleavable linker as discussed above, the Examiner reasonably interprets the “-L1-CM1-CM2-L2-“ linking group of Brundo which links the tissue binding moiety (e.g. X) to the active agent (e.g. A) as taught by Brundo above corresponds to the recited limitation wherein “L1” of Formula (I) of instant claim 1 is a cleavable linker selected from as recited and required within instant claim 12.It would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have combined the click target of Formula (I) and the click prodrug of Formula (II) which are both taught by Brundo above to create a new delivery agent containing both the click target of Formula (I) and the click prodrug of Formula (II) as taught by Brundo above as within the scope of the artisan as combining prior art elements according to known compositions and methods to yield predictable results. One of ordinary skill in the art would have been motivated to deliver an active agent to a target tissue of a subject. One of ordinary skill in the art would have had a reasonable expectation of success to combine Formula (I) and Formula (II) as taught by Brundo above to create a new delivery agent as discussed above, because Brundo separately teaches Formula (I) and Formula (II) in a method of delivering an active agent to a subject as discussed above.
Furthermore, MPEP 2144.06(I) states “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be used for the same purpose, in order to form a third composition to be used for the very same purpose … [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA1980)(citations omitted).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have combined the click target of Formula (I) and the click prodrug of Formula (II) both taught by Brundo above to create a new delivery agent as discussed above as within the scope of the artisan as combining prior art elements according to known compositions and methods to yield predictable results. One of ordinary skill in the art would have been motivated to create the new delivery agent comprising the cleavable linker as taught by Brundo above in order to release and deliver the active agent to the target tissue of the subject as taught by Brundo above. One of ordinary skill in the art would have had a reasonable expectation of success to have combined the click target of Formula (I) and the click prodrug of Formula (II) of Brundo, because Brundo teaches the first click motif of Formula (I) and the second click motif of Formula (II) are selected such that the first click motif is capable of chemically reacting with the second click motif to form a covalent bond as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
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.
(I) Claims 1-3, 10, 14-16 and 20-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21 and 27 of copending Application No. 17/281,025 (Applicant: North Carolina State University, amended claim set filed 01/07/2026) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to delivering an active agent to a target tissue.
Reference claim 27 recites a method of maintaining or reducing the size of a tumor in a subject in need thereof, comprising the steps of:
(i) injecting into the tumor a click target consisting of Formula I, which is depicted as X-L1-CM1, wherein X represents a tumor tissue binding moiety configured to chemically react with an amine group in an extracellular matrix protein in the tumor tissue, thereby forming a direct bond with the tumor tissue; L1 represents a linking group; and CM1 represents a first click motif;
(ii) administering to the subject a click prodrug consisting of Formula II, which is depicted as A-L2-CM2, wherein A represents an anti-cancer drug, L2 represents a linking group; and CM2 represents a second click motif complementary to the first click motif; wherein the first click motif is capable of chemically reacting with the second click motif to form a covalent bond; and
(iii) repeating step (ii), thereby maintaining or reducing the size of the tumor in the subject.
The Examiner respectfully notes that “direct bond” is defined in the specification of ‘025 to refer to a single, double or triple bond between two groups (e.g. a covalent bond, required in instant claim 22, lines 12-13), see Specification, pg. 12, lines 14-15.
Reference claim 1 recites a method of delivering an active agent to a target tissue in a subject, the method comprising:
(i) contacting the target tissue with a click target consisting of Formula I, which is depicted as X-L1-CM1, wherein X represents a tissue binding moiety configured to chemically react with an amine group in an extracellular matrix protein in the target tissue, thereby forming a direct bond with the tumor tissue; L1 represents a linking group; and CM1 represents a first click motif; and
(ii) contacting the target tissue with a click prodrug consisting of Formula II, which is depicted as A-L2-CM2, wherein A represents an active agent, L2 represents a linking group; and CM2 represents a second click motif complementary to the first click motif; wherein the first click motif is capable of chemically reacting with the second click motif to form a covalent bond.
Reference claim 21 reads on instant claim 20.
With respect to the limitation “a therapeutically effective amount of a compound consisting of Formula I” as required in instant claim 1, line 3, and instant claim 22, line 3, the Examiner respectfully notes that ‘025 recites the anti-cancer drug is comprised within Formula II as discussed above, wherein the second click motif comprised within Formula II above is capable of chemically reacting to form a covalent bond with the first click motif, which is comprised within Formula (I) as discussed above.
Therefore, the Examiner respectfully notes when Formula I is injected into the tumor tissue, the anti-cancer drug comprised within Formula II will also be injected, thereby maintaining or reducing the size of a tumor in a subject in need thereof.
Consequently, the Examiner reasonably interprets when the click target of Formula II contains an anti-cancer drug as discussed above, for maintaining or reducing the size of a tumor, the amount injected of Formula I as required by instant claims 1 and 22 as discussed above is a “therapeutically effective amount” in order to maintain or reduce the size of the tumor is met by the recitations of ‘025 above.
Thus, the limitation of a therapeutically effective amount of a compound consisting of Formula I” as required within instant claim 1, line 3, and instant claim 22, line 3 is met by the recitations of ‘025.
As a result the recitations of “025 read on instant claims 1-3, 10, 14-16 and 20-22.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(II) Claims 4-6, 12-13 and 17-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 13-16, 21-22 and 27 of copending Application No. 17/281,025 (Applicant: North Carolina State University, amended claim set filed 01/07/2026) in view of Brundo et al. (Published 02 April 2020, Filed 30 September 2019, WO-2020069488-A1, IDS filed 04/14/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to delivering an active agent to a target tissue.
‘025 recites as written above. ‘025 further recites in:
Reference claim 6 wherein the tissue binding moiety comprises a hydroxysuccinimidyl (NHS) group;
Reference claim 13 recites wherein L2 represents a cleavable linker, wherein the cleavable linker is selected from and includes a hydrolytically cleavable linker, a photocleavable linker and an enzymatically cleavable linker; and
Reference claim 22 recites wherein contacting the target tissue with a click target comprises injecting a pharmaceutical composition comprising the click target into the target tissue.
Reference claims 14 and 15 read on instant claims 13 and 14 respectively.
Reference claim 16 reads on instant claim 15 and corresponds to instant claims 16-19.
Although, ‘025 does not recite wherein the tissue binding moiety comprises (a) a sulfo-hydroxysuccinimidyl (sNHS) group, required in instant claim 4 and (b) a maleimide group, required in instant claims 5-6.
However, in the same field of endeavor of delivering an active agent to a target tissue of a subject with the click target, with respect to limitations (a)-(b), Brundo teaches delivering an active agent to a target tissue of a subject, comprising contacting the target tissue with a click target defined by Formula I, which is depicted as X-L1-CM1, wherein X represents a tissue binding moiety; L1 is absent or represents a linking group; and CM1 represents a first click motif, see pg. 1, lines 18-23; and
contacting the target tissue with a click prodrug defined by Formula II, A-L2-CM2, wherein A represents an active agent, L2 is absent or represents a linking group; and CM2 represents a second click motif complementary to the first click motif, see pg. 1, lines 23-28;
wherein the tissue binding moiety comprises a functional group capable of chemically reacting with an amine group in a peptide (e.g. an extracellular matrix protein) to form a covalent bond, such as a hydroxysuccinimidyl (NHS) group or a sulfo-hydroxysuccinimidyl (sNHS) group (e.g. the tissue binding moiety required in instant claim 4 and 7-9), see pg. 20, lines 12-15;
or the tissue binding moiety comprises a functional group capable of chemically reacting with a thiol group in a peptide to form a covalent bond, such as a maleimide group (e.g. the tissue binding moiety, required in instant claims 5 and 6), see pg. 20, lines 18-20.
With respect to the limitation wherein L1 represents a cleavable linker as required in instant claim 12; the Examiner respectfully notes that reference claim 13 of ‘025 as discussed above recites that L2 is a linker within the click target of Formula II above, which can be linked to Formula I above, and where the Examiner further respectfully notes Formula I contains the linker L1, and wherein reference claim 13 of ‘025 recites L2 can be a cleavable linker as discussed above. Thus, the limitation wherein L1 represents a cleavable linker as required in instant claim 12 is made obvious based on the recitations of reference claim 13 as recited by ‘025 as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated limitations (a)-(b) into the recitation of claim 1 or claim 22 of ‘025 as discussed above by using the teachings of Brundo as discussed above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to deliver an active agent to a target tissue in a subject as recited in reference claim 1 of ‘025 as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success to have incorporated limitations (a)-(b) into the recitations of either reference claim 1 or claim 22 of ‘025 above, as both ‘025 and Brundo are drawn to click targets in delivering an active agent into a target tissue of a subject as discussed above.
Thus, the claimed invention as a whole would have been obvious over the combined recitations of ‘025 and the teachings of the prior art.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed in this action.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691