DETAILED ACTION
This Office action details a final action on the merits for the above referenced application No. Claims 1, 4-9, and 12-21 are pending in this application.
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 .
Status of Claims
Claims 1, 17, and 20 are amended. Claims 2-3, and 10-11 are cancelled. Claim 21 is new.
Response to Amendment
The amendments filed on 5 Feb. 2026 have been entered.
Response to Arguments
In view of Applicants amendments, the rejection of claims 1, 4-9, and 12-30 under 35 USC 112(b) for failing to particularly point out and distinctly claim the subject matter is withdrawn.
In view of Applicants amendments, the rejection of claim 7 under 35 USC 112(d) as being of improper dependent form for failing to further limit the subject matter is withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4-7, 12-15, and 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chung et al. (US 2011/0262354 A1; filed 13 Jan. 2007), in view of Liu et al. (Bioorg. Med. Chem. Lett.; published 2007) and Chen et al. (Bioconjugate Chem.; published 2005) for the reasons cited in the Office action filed on 5 Sep. 2025.
Claim(s) 1, 4-9, and 12-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chung et al. (US 2011/0262354 A1; filed 13 Jan. 2007), in view of Liu et al. (Bioorg. Med. Chem. Lett.; published 2007) and Chen et al. (Bioconjugate Chem.; published 2005), in further view of Vlahov et al. (WO 2007/022494 A1; published 22 Feb. 2007) and Safavy et al. (J. Med. Chem.; published 1999) for the reasons cited in the Office action filed on 5 Sep. 2025.
Applicants Arguments
Applicants assert that Chung is silent with respect to conjugates of cyanine dyes with anti-cancer agents. Chung fails to disclose or suggest a linker comprising a C1-C6 moiety and an amide moiety. Liu, Chen, Vlahov, and Safavy all fail to cure the deficiencies of Chung.
Applicant's arguments filed 13 Feb. 2026 have been fully considered but they are not persuasive. Chung provides for cyanine-containing compounds for cancer imaging and treatment where exemplary cyanine-containing compounds include the MHI-148 that reads on the targeting ligand of formula I wherein R1=H and R5=(CH2)5CO2H (C5 alkyl substituted by oxygen containing group). At Figs., Chung shows that MHI-148 can enable in vivo imaging lung cancer and lymphoma. MHI-148 shows the ability to detect multiple tumors of different sizes following in vivo administration. MHI-148 shows the ability to detect spontaneous tumor development. Accordingly, Chung establishes MHI-148 as a suitable tumor targeting ligand for a wide range of tumors. At [0020], Chung teaches and motivates conjugating the cyanine-containing compounds therein to a radioactive isotope or other functional group. At [0122], Chung teaches providing a desired level of active agent or conjugate in the blood stream. At for example [0005], Chung teaches the conjugation amenable N-hydroxysuccinamide group. At [0162], Chung teaches administering the cyanine-containing compound of the invention in combination with an antineoplastic therapeutic agent (i.e. co-administration). The cyanine containing compound antineoplastic agent can be administered in fixed combination. At [0164], Chung teaches paclitaxel as an exemplary chemotherapeutic agent. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Chung by conjugating for example the MHI-148 cyanine compound that accumulates in a wide range of cancer types to a therapeutic agent such as a radioisotope or paclitaxel using a carboxyl (C1 moiety) linker such as NHS to form an amide as taught by Chung because that conjugate would have been expected to advantageously enable combination imaging and therapy of a wide range of cancer types where the combination imaging and therapy treats and images the cancer types by different mechanisms.
Like Chung, Liu provides for composition comprising a fixed combination of a tumor targeting agent (glucose) and the chemotherapeutic agent paclitaxel wherein the fixed combination provides enhanced treatment of cancer cells. In this case, Liu teaches and motivates conjugating the tumor targeting agent to paclitaxel using a succinimide linker. According to Liu, the modification on 2’-hydroxyl group of paclitaxel with succinic acid (C4 moiety) appears to reduce the toxicity of paclitaxel. It enhanced selectivity of uptake and cytotoxicity for cancer cells. Chen teaches and motivates a linker strategy for cyanine compounds analogous to MHI-148 where the linker strategy places a conjugation amenable amino group on the cyanine containing compound. A recognized advantage is the strongest reason to combine. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Chung by conjugating for example the MHI-148 tumor targeting cyanine compound to paclitaxel using a succinic acid linker that connects to amine on the cyanine containing compound to form an amide and the hydroxyl on paclitaxel to form a succinic ester as taught by Chung and Liu because the conjugating would have been expected to advantageously enable a fixed combination having reduced toxicity and enhanced cytotoxicity for cancer cells.
New Grounds of Rejection
Claim Objections
Claim 1 is objected to because of the following informalities: in claim 1, the comma before the period at the end of the claim should be removed. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 21 is 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. In claim 21, the recitations of “(BCNU)”, “(cis-DDP)”, “(VP-16)”, “(5-FU)”, “(CCNU)”, “(MTX)”, “(o.p’-DDD)”, “(HMM)”, “(methyl-GAG, methyl glyoxal bis-guanylhydrazone (MGBG))”, “(MGBG)”, “(methyl-CCNU)”, and “(VM-26)” are indefinite because it is not clear if those recitations are merely examples, abbreviations, or required limitations.
Claim 21 contains the trademark/trade names “VP-16”, “CCNU”, “HMM”, and “VM-26”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names are used to identify/describe pharmaceutical products, air flow spoilers, and computer hardware and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 103
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chung et al. (US 2011/0262354 A1; filed 13 Jan. 2007), in view of Liu et al. (Bioorg. Med. Chem. Lett.; published 2007) and Chen et al. (Bioconjugate Chem.; published 2005).
Chung et al. teach cyanine containing compounds for cancer imaging and treatment (see title). Chung et al. teach methods of using cyanine containing compounds for cancer cell imaging, cancer cell growth inhibition, and detection of cells (see abstract). Chung et al. teach cyanine conjugates where the cyanine emits fluorescence in the NIR region (see [0003]). Chung et al. teach providing the desired level of active agent or conjugate in the bloodstream or tissue (see [0122]). Chung et al. teach examples of cyanine dyes of formula C
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such as MHI-148 (R5=H, R=(CH2)5COOH), MHI-25 (R5=H, R=(CH2)4SO3H), MHI-78 (R5=H, R=(CH2)2OH) and IR780 (R5=H, R=(CH2)2CH3). R5 may be selected from OH, NH2 (conjugate amenable functional groups) (see [0046]). These compounds read on targeting ligands of formula
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wherein R1=H, and R2= C3 alkyl (IR780), C4 alkyl sulfur containing group (MHI-25), or a C5 alkyl substituted with an oxygen containing group (MHI-148, emission 850 nm, [0078]. Chung et al. teach MHI-148 can image lung cancer and lymphoma (see Fig. 4) and the preferential uptake of IR 780 by cancerous tissue but not normal cells (see Figs. 14-20). Uptake is completely abolished by BSP (inhibitor of organic anion transporters). Chung et al. teach N-hydroxysuccinimide (see [0010]). The compounds of the invention may be administered in combination with other antineoplastic therapeutic agents and may be administered in a fixed combination (see [00162]). Chemotherapeutic agents include paclitaxel and other taxanes and octreotide ([0164]). Chung et al. teach methods of treating cancer comprising administering a cytotoxic amount of a cyanine-containing compound to cancer cells ([0013]). Chung et al. teach that esters of the compounds of the present invention can be prepared by functionalization of a hydroxyl group present within the molecular structure of the compound…Esters can be made by reaction with a carbonylating agent, e.g. acetic anhydride ([0135]). Compounds of the invention may be tagged with radioactive groups or other functional groups as known in the art ([0020]).
Chung et al. do not teach a conjugate of one of the above compounds comprising anti-cancer drug and a linker comprising a carboxyl (C1) or succinic (C4) moiety and an amide wherein the linker connects one of the above compounds to the anticancer drug wherein the anticancer drug is paclitaxel.
Liu et al. teach the synthesis of 2’-paclitaxel methyl 2-glucopyranosyl succinate for specific targeted delivery to cancer cells (see title). Liu et al. teach that paclitaxel is a potent anticancer drug used for the treatment of breast, ovarian and lung carcinomas. Among the most notable paclitaxel derivatives synthesized so far are those in which the C-2’ and C-7’ hydroxyl groups of the molecule are engaged in a functional group that collapses, upon in vivo activation, releasing paclitaxel (see pg. 617). Liu et al. teach compound 5
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. Liu et al. teach that although modification on the 2’-hydroxyl group of paclitaxel with succinic acid appeared to reduce the toxicity of paclitaxel on MCF-7 cell growth, this linker maintained the activity of paclitaxel upon the concentration used and could be used for the next conjugation with 2’-glucopyranose (see pg. 618). Liu et al. teach that the conjugation of glucose could reduce the toxicity of paclitaxel and showed the safety on human epithelial cells. It also enhanced the selectivity of glucose uptake and cytotoxicity for cancer cells (see pg. 619). Liu et al. teach fluorescein labeled octreotide conjugated paclitaxel (see pg. 619).
Chen et al. teach a novel approach to a bifunctional photosensitizer for tumor imaging and phototherapy (see title). Chen et al. teach that a clinically relevant photosensitizer (HPPH) was linked with a cyanine dye and the resulting conjugate was found to be an effective tumor imaging and photosensitizing agent. Compared to HPPH, the presence of the cyanine dye moiety in the conjugate produced a significantly higher uptake in tumor than skin (see abstract). Chen et al. teach a synthesis scheme for conjugate 5
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(see scheme 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compositions of Chung et al. (composition comprising a fixed combination of a cancer targeting cyanine compound such as MHI-148 and anti-cancer drug such as paclitaxel) so that the fixed combination get formed by covalently tethering the cyanine targeting compound having an amino reactive group to the paclitaxel anticancer compound using a C1-C6 moiety such as such a succinic moiety that forms an amide as taught by Chung et al., Liu et al., and Chen et al. that fixed combination comprising the covalent tether would have been expected to advantageously enable a combination exhibiting reduced toxicity and enhanced cytotoxicity.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/SEAN R. DONOHUE/
Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618