DETAILED ACTION
The present application is a domestic application filed 02 April 2024, which is a divisional of US Application No. 17/551,689 (now US Patent No. 12,285,441), filed 15 December 2021, which is a divisional of US Application No. 16/423,921 (now US Patent No. 11,229,665), filed 28 May 2019, which is a divisional of US Application No. 15/411,958 (now US Patent No. 10,342,878), filed 20 January 2017, which is a continuation-in-part of US Application No. 14/308,972 (now US Patent No. 9,572,832), filed 19 June 2014, which claims priority to US Provisional Application No. 61/871,352, filed 29 August 2013.
Claims 1-14 are pending in the current application and are examined on the merits herein.
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 .
Priority
The present application is a domestic application filed 15 December 2021 is acknowledged. The application is a divisional of US Application No. 16/423,921 (now US Patent No. 11,229,665), filed 28 May 2019, which is a divisional of US Application No. 15/411,958 (now US Patent No. 10,342,878), filed 20 January 2017, which is a continuation-in-part of US Application No. 14/308,972 (now US Patent No. 9,572,832), filed 19 June 2014, which claims priority to US Provisional Application No. 61/871,352, filed 29 August 2013.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). Also, see MPEP 706.02 (section VI).
The disclosure of the prior-filed application(s), to US Provisional Application No. 61/871,352, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Specifically, these applications fail to provide support for the conjugation of nimesulide to hyaluronic acid. Therefore the effective filing date of claims 1 and 2 is seen to be the effective filing date of the US Application No. 14/308,972 (now US Patent No. 9,572,832), 19 June 2014.
If applicant disagrees, applicant should present a detailed analysis as to why the claimed subject matter has clear support in the earlier priority applications. Applicant is reminded that such priority for the instant limitations requires written description and enablement under 35 U.S.C. § 112, first paragraph.
In clarifying the priority date of the instant claims, applicant should note or address whether the art rejections are prior to the priority date of the instant claims and whether said art occurred more than one year prior to said priority date. Applicant will note that the art rejections are under both 35 U.S.C. § 102(a) and 102(b) because the priority date of the instant claims is in question
Claim Objections
Claim(s) 10 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Closest Prior Art
Zhong et al. (European Journal of Medicinal Chemistry, 2012, vol. 47, pp. 432-444, cited in IDS submitted 04 April 2024) teach JCC76, a nimesulide analog. JCC76 is a derivative of nimesulide, which has been modified to have an amide group. The compound has activity against breast cancer.
However, there is no teaching to modify nimesulide itself to have an amino group for direct conjugation to a carrier, let alone hyaluronic acid. Furthermore, there is no teaching or suggestion for using a modified nimesulide for treating pancreatic cancer.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
I. Lenalidomide:
Claim(s) 1-3, 5-7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Campisi et al. (US Patent Application Publication No. 2011/0189265, cited in PTO-892) in view of Segler et al. (Cancer Chemoter. Pharmacol., 2012, vol. 69, pp. 1393-1406, cited in PTO-892) and further in view of Rozewski et al. (The AAPS Journal, 2012, vol. 14, no. 4, pp. 872-882, cited in PTO-892).
Campisi et al. teach bioconjugates for use in cancer treatment, the bioconjugates obtained by the conjugation between hyaluronic acid (HA) and a chemotherapeutic product (abstract). Drug conjugates have been prepared with direct bonds and indirectly via linkers (para [0014]). Here, the HA forms a covalent bond via the carboxylic group of HA, which forms an ester or amide bond with the functional group of the spacer/linker (para [0071]). Chemotherapeutic agents can include for example irinotecan, doxorubicin, paclitaxel, cis-platinum, and 5-flurouracil (abstract). The molecular weight of the HA ranges from 400 to 3,000,000 Da, from 5,000 to 1,000,000 Da, or from 30,000 to 500,000 Da (claims 45-47). The anti-tumoral drug/chemotherapeutic is covalently bound through a spacer, which forms an ester bond with HA (claim 48). The bioconjugate can be used to treat tumors of the pancreas (claim 37). Campisi et al. teach the conjugate improves the solubility and bioavailability of insoluble drugs (see e.g. para [0013], [0014], [0016], [0040]).
Campisi et al. do not expressly disclose lenalidomide (present claim 1).
Segler et al. reviewed phase I-III clinical trials on the use of lenalidomide for treating pancreatic cancer (abstract). In a case report, a patient with metastatic pancreatic adenocarcinoma was treated with weekly gemcitabine (p.1987, last para). When the carbohydrate antigen 19-9 increased after 2 months, daily lenalidomide was administered, which resulted in a decrease in the antigen level lasting for >33 months (p.1400, first para). Segler et al. teach the structure of lenalidomide:
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(fig. 1).
Rozewski et al. teach lenalidomide is moderately soluble (p.872, second para). Rozewski et al. teach “Doses administered to mice were limited by solubility of lenalidomide in the PBS dosing solution…Due to solubility limitations which prevented further dose escalation, a maximum tolerated dose was not established” (p.875, first para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to conjugate lenalidomide with HA.
The skilled artisan would have been motivated to conjugate lenalidomide with HA, because lenalidomide is only moderately soluble, and conjugating anti-cancer agents to HA improves the drug’s solubility and bioavailability. Thus, it would have been obvious to substitute one anti-cancer agent of Campisi et al., with another, with a reasonable expectation of success. Furthermore, it would have been obvious to administer the lenalidomide-HA conjugate to treat pancreatic cancer, because lenalidomide is a known anti-cancer agent, which can be used to target/treat pancreatic cancer.
As can be seen by Segler et al., lenalidomide contains an amino group. While Campisi et al. teach forming HA-ester conjugates, Campisi et al. also acknowledge amide bonds can be formed with the carboxylic acid moiety of HA. Furthermore, one of ordinary skill in the chemical arts would have known conjugation of an amine with a carboxylic acid group (of HA), would result in an amide bond. Thus, it would have been obvious to form an HA-lenalidomide conjugate, wherein the amino group of lenalidomide forms an amide bond with the carboxylic group of HA. Additionally, while Campisi et al. teach the use of a spacer, Campisi et al. acknowledge drug conjugates have been prepared with direct bonds. Thus, it would have been obvious to prepare a conjugate with a direct bond.
Furthermore, it would have been obvious to conjugate lenalidomide indirectly to HA through a linker, because this is expressly taught by Campisi et al. for preparing HA-anticancer drug conjugates.
The recitation “wherein the nimesulide is hydrogenated nimesulide, such that the hydrogenated nimesulide is covalently linked to the carboxylic group of hyaluronic acid…” in claim 9 does not actually require or limit the active compound to nimesulide.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 2 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Campisi et al. in view of Segler et al., and Rozewski et al. as applied to claims 1-3, 5-7 and 9 above, and further in view of Luo et al. (US Patent Application Publication No. 2004/0234497, cited in PTO-892).
Campisi et al. teach as discussed above.
While Campisi et al. teach the use of a spacer, Campisi et al. do not expressly disclose directly conjugating HA with lenalidomide (present claims 2 and 6).
Segler et al. and Rozewski et al. teach as discussed above.
Luo et al. teach the preparation of glycosaminoglycan (GAG) conjugates with biologically active molecules (HA). The biologically active agent includes antitumoral drugs (claim 9). The GAG includes hyaluronic acid (claim 7). Luo et al. teach preparing HA conjugates by forming an amide directly with the active drug (claim 11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to directly conjugate lenalidomide with HA.
As can be seen by Segler et al., lenalidomide contains an amino group. While Campisi et al. teach forming HA-ester conjugates, Campisi et al. also acknowledge amide bonds can be formed with the carboxylic acid moiety of HA. Furthermore, one of ordinary skill in the chemical arts would have known conjugation of an amine with a carboxylic acid group (of HA), would result in an amide bond.
And while Campisi et al. teach using a spacer, it would have been obvious to form direct HA-lenalidomide conjugates, because Luo et al. teach preparing HA-antitumor conjugates by forming direct bonds.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 4 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Campisi et al. in view of Segler et al., and Rozewski et al. as applied to claims 1-3, 5-7 and 9 above, and further in view of Prestwich et al. (Bioconjugate Chemistry, 1999, vol. 10, no. 5, cited in PTO-892).
Campisi et al. teach as discussed above.
Campisi et al. do not expressly disclose wherein the linker is ADH, polypeptide, peptide, lipid, and amino acid (present claims 4 and 8).
Segler et al. and Rozewski et al. teach as discussed above.
Prestwich et al. teach preparing a hyaluronic acid-taxol conjugate, wherein the two were linked via adipic dihydrazide (ADH), (abstract). The use of the ADH spacer allowed them to synthesize HA bioconjugates with different amounts of taxol. They showed selective toxicity towards human cancer cell lines.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to conjugate HA with lenalidomide via adipic dihydrazide (ADH), because it allows for modifying the amount of lenalidomide conjugated to the HA. The ordinary artisan would have had a reasonable expectation of success because ADH has successfully been used to conjugate an anti-cancer agent to HA, and was found to selectively target human cancer cells.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
II. Gemcitabine
Claim(s) 1-3, 9 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Campisi et al. (cited above) in view of Moysan et al. (Molecular Pharmaceutics, published September 2012, vol. 10, pp. 430-444, cited in IDS submitted 03 April 2024).
Campisi et al. teach as discussed above.
Campisi et al. do not expressly disclose gemcitabine (present claim 11).
Moysan et al. teach gemcitabine is a known anticancer agent with activity against a wide range of solid tumors, including pancreatic tumors (abstract, p.430, second para). Gemcitabine is rapidly deaminated in vivo, causing a short plasma half-life. Moysan et al. teach prodrugs have been prepared to overcome some of the current problems with gemcitabine, which include drug resistance, and rapid drug metabolism (abstract).
Moysan et al. teach gemcitabine is typically modified at one of two sites, the 5’-OH position, or the 4-NH2 site:
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(p.430). Moysan et al. teach examples wherein gemcitabine has been modified with a PEG polymer through the 4-N-position (p.431, figure 2, compounds C and E for example). Moysan et al. teach “confocal analysis showed PEG-gemcitabine colocalization in lysosome and endosome after 24 h incubation and an enhanced retention in cancer cells after 3 days of incubation in comparison to native gemcitabine” (p.434, last paragraph). Moysan et al. teach “pharmacokinetic studies have shown consistently higher bioavailability (21 times) of PEG-gemcitabine over native gemcitabine, after 1 h of intravenous administration in mice” (p.434, last paragraph).
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Moysan et al. teach gemcitabine conjugates wherein the 4-(N)-amino group of gemcitabine was linked to the COOH of PEG (p.434-435, bridging paragraph). Moysan et al. teach polymer conjugation to gemcitabine has been shown to increase the conjugates cytotoxicity against cancer cells (p.435, first paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to directly/indirectly conjugate the amine of the gemcitabine to the carboxylate of the hyaluronic acid.
The skilled artisan would have been motivated to conjugate the amine of the gemcitabine to the carboxylate of the hyaluronic acid to improve the bioavailability of the gemcitabine anti-cancer agent, because Moysan et al. found conjugating gemcitabine to a polymeric carrier improved the drug’s bioavailability, and Campisi et al. teach the use of HA to improve the bioavailability of anti-cancer agents. The ordinary artisan would have been motivated to conjugate via the amino group to form an amide, because Moysan et al. teach conjugating gemcitabine via the 4’-NH2 group.
The ordinary artisan would have been motivated to conjugate the two via a linker, because Campisi et al. teach drug conjugates have been prepared directly and indirectly, and teach a variety of suitable spacers. Thus, the ordinary artisan would have had a reasonable expectation of success in preparing a drug conjugate directly/indirectly.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 4, 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Campisi et al. in view of Moysan et al. as applied to claims 1-3, 9 and 11-13 above, and further in view of Prestwich et al. (cited above).
Campisi et al. teach as discussed above.
Campisi et al. do not expressly disclose wherein the linker is ADH, polypeptide, peptide, lipid, and amino acid (present claims 4, 13 and 14).
Moysan et al. teach as discussed above.
Prestwich et al. teach as discussed above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to conjugate HA with gemcitabine via adipic dihydrazide (ADH), because it allows for modifying the amount of anti-cancer agent conjugated to the HA. The ordinary artisan would have had a reasonable expectation of success because ADH has successfully been used to conjugate an anti-cancer agent to HA, and was found to selectively target human cancer cells.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching 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.
Claims 1-9 and 11-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 10,342,878 in view of Segler et al., Moysan (cited above) and Prestwich (cited above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference patent are drawn towards a method of treating colon cancer or glioblastoma, comprising a step of administering to a subject in need thereof a therapeutically effective amount of a compound consisting of a conjugate of hyaluronic acid and active compound. The active compound is selected from the group consisting of lenalidomide, nimesulide and celecoxib. The molecular weight of HA ranges from 10,000 Da to 2,000,000 Da (claim 2).
The claims of the ‘878 Patent do not expressly disclose treating pancreatic cancer (claim 1). The claims of the ‘878 Patent do not expressly disclose administering gemcitabine.
Segler et al. teach as discussed above.
Moysan et al. teach as discussed above. Moysan et al. also teach gemcitabine can be used to treat colon cancer.
Prestwich et al. teach as discussed above.
The skilled artisan would have been motivated to conjugate the amine of the gemcitabine to the carboxylate of the hyaluronic acid to improve the bioavailability of the gemcitabine anti-cancer agent, because Moysan et al. found conjugating gemcitabine to a polymeric carrier improved the drug’s bioavailability, and Campisi et al. teach the use of HA to improve the bioavailability of anti-cancer agents.
In the same field of endeavor for treating colon cancer as the claims in the reference Patent, Moysan et al. found gemcitabine can also be used to treat pancreatic cancer. Thus, the ordinary artisan would have been motivated to administer the gemcitabine conjugate to treat pancreatic cancer.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to conjugate HA with any of the claimed anti-cancer agents via adipic dihydrazide (ADH), because it allows for modifying the amount of anti-cancer agent conjugated to the HA. The ordinary artisan would have had a reasonable expectation of success because ADH has successfully been used to conjugate an anti-cancer agent to HA, and was found to selectively target human cancer cells.
With respect to lenalidomide, the ordinary artisan would have been motivated to administer the lenalidomide HA conjugate to treat pancreatic cancer, because Segler et al. teach it is known for treating pancreatic cancer.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
Prosecution Insights