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 .
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.
This office action is a response to applicant’s communication submitted March 6, 2024. This application is a 371 of PCT/US2022/047811 filed 10/26/2022 and claims benefit to PRO 63/274,374 filed 11/01/2021.
Claims 1-27 are pending in this application.
Claim Rejections - 35 USC § 112 (b)
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 27 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.
Regarding claim 27: Claim 27 recites “wherein said gemcitabine is administered from 1 minute to 1 week.”. It is unclear whether the administration is meant to describe a controlled release formulation, similar to instant claim 9, or the administration is in reference to another undisclosed method step. In the latter interpretation it is unclear as to what that method step is. Thus the lack of clarity renders the claim indefinite.
Claim Rejections - 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.
Claims 1-6 and 16-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tang (Int. J. Pharmaceutics, 2021, IDS filed March 6, 2024, available online April 30, 2021).
Regarding claims 1-6 and 16-20: Tang teaches the development of a liposomal formulation comprising gemcitabine to zebularine in a molar ratio of 2:1 (i.e. 1:0.5, pg. 5, col. 2, section 3.4.1). Tang teaches the w/w was found to be 4.0% for gemcitabine and 1.9% for zebularine (pg. 5, col. 2, section 3.4.1). To obtain a 2:1 drug loading (DL) for gemcitabine and zebularine in pSL, the amount of gemcitabine and zebularine was varied during loading. Briefly, gemcitabine (0.75 or 1.5 mg) and zebularine (0.75, 1.0 or 1.5 mg) were dissolved (suspended) in 20 µL PBS pH 7.4 (pg. 2, col. 1, para. 2). The formulations were intravenously injected (i.e. injectable, pg. 5, col. 2, last para.).
Claim Rejections - 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.
Claims 21-22, 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Tang (Int. J. Pharmaceutics, 2021, IDS filed March 6, 2024, available online April 30, 2021) as applied to claims 1-6 and 16-20 above.
Regarding claims 21-22, 24-25: As discussed above, Tang teaches the composition of claims 1-6 and 16-20 comprising gemcitabine and zebularine.
Tang does not explicitly teach a method of treating a patient suffering from cancer.
However, Tang suggests co-delivery of zebularine using liposomes could provide multifaceted benefits in gemcitabine therapy for pancreatic cancer treatment (abstract, pg. 8, cols. 1-2, bridging para.). Tang establishes that zebularine co-delivered with gemcitabine using a nanomedicine carrier pSL, capable for intracellular delivery (pg. 8, cols. 1-2, bridging para.).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to apply the composition of Tang for the treatment of pancreatic cancer as suggested by Tang. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as Tang recognizes the therapeutic potential for the composition to be used for this purpose, and teaches that compositions comprising gemcitabine and zebularine are known in the art for treating this disease.
Claims 23 and 26 is rejected under 35 U.S.C. 103 as being unpatentable over Tang (Int. J. Pharmaceutics, 2021, IDS filed March 6, 2024, available online April 30, 2021) as applied to claims 1-6, 16-22, 24-25 above in view of Cordelier (WO 2017158396, cited on PTO-892).
Regarding claim 23: As discussed above, it would have been prima facie obvious to apply the composition of Tang for the treatment of pancreatic cancer. Tang renders obvious the liposomal co-delivery of gemcitabine with zebularine, a dual cytidine deaminase inhibitor for treatment of pancreatic cancer (abstract).
Tang does not teach wherein the cancer is pancreatic ductal adenocarcinoma.
However, Cordelier teaches cytidine deaminase inhibitors for the treatment of pancreatic cancer (title, abstract). Cordelier teaches pancreatic ductal carcinoma (PDA) is the most common type of pancreatic cancer and has been treated with combination cytotoxic therapies comprising gemcitabine (pg. 1, lines 9-10, 17-18). Cordelier teaches in patients with PDA resistant to gemcitabine, cytidine deaminase (CDA) is overexpressed (pg. 3, lines 5-8).
Taken together it would have been prima facie obvious to a person of ordinary skill to apply the method of treating pancreatic cancer of Tang to the treatment of pancreatic ductal adenocarcinoma specifically as taught by Cordelier. A person of ordinary skill in the art would have the motivation to do so with a reasonable expectation of success as the art recognizes both cydidine deaminase inhibitors and gemcitabine as viable treatments for this cancer type.
Regarding claim 26: As discussed above, it would have been prima facie obvious to apply the composition of Tang for the treatment of pancreatic cancer. Tang renders obvious the liposomal co-delivery of gemcitabine with zebularine, a dual cytidine deaminase inhibitor for treatment of pancreatic cancer (abstract).
Tang does not teach wherein the gemcitabine and zebularine are administered at an interval.
However, Cordelier teaches therapeutic regimens, known as maintenance regimens, to keep the subject in remission for long periods of time which employs continuous therapy (e.g. administering a drug at a regular interval) are a known practice in the art (pg. 4, lines 15-20).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to administer the composition of Tang at a regular interval. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as it is a known technique in the art of cancer therapeutics in order to keep the subject in remission to effectively treat the underlying condition.
Claims 7-10, 12-13, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Tang (Int. J. Pharmaceutics, 2021, IDS filed March 6, 2024, available online April 30, 2021) as applied to claims 1-6, 16-22, 24-25 above in view of Belyakov (WO 2010/118013, IDS filed March 6, 2024).
Regarding claims 7-10 and 27: Tang teaches the composition according to claim 4. Tang renders obvious the liposomal co-delivery of gemcitabine with zebularine, a dual cytidine deaminase inhibitor for treatment of pancreatic cancer (abstract).
Tang does not teach wherein the biocompatible excipient comprises a biocompatible polymer that forms a depot in situ, in which the depot is biodegradable, provides release of gemcitabine from 1 minute to 1 week, and is in microparticle form.
However, Belyakov teaches a combination of cytidine-based antineoplastic drugs with cytidine deaminase inhibitors and use thereof in the treatment of cancer (title). Belyakov teaches gemcitabine is a cytidine-based antineoplastic drug that has been used in conjunction with CDA inhibitors (pg. 3, lines 20-23). Belyakov teaches injectable depot forms may be made by forming microencapsule matrices of the subject compositions in biodegradable polymers such as polylactide-polyglycolide (pg. 43, lines 27-28). Depending on the ratio of drug to polymer, and the nature of the particular polymer employed, the rate of drug release may be controlled (pg. 43, lines 29-30). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissue (pg. 43, lines 31-33).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of Tang using biodegradable polymers such as polylactide-polyglycolide to make a microparticle depot formulation as suggested by Belyakov. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as it is a known technique in the art in combination therapies combining gemcitabine and CDA inhibitors in order to control the rate of drug release for the purpose of treating cancer in a subject. Although the prior art does not explicitly state the release time is between 1 minute to 1 week as claimed, the art establishes the rate of release is a result effective variable, and thus a person of ordinary skill in the art would arrive at the claimed range through routine optimization (See MPEP 2144.05 (II)).
Regarding claims 12-13: Tang teaches the composition according to claim 4. Tang teaches the liposomal co-delivery of gemcitabine with zebularine, a dual cytidine deaminase inhibitor for treatment of pancreatic cancer (abstract).
Tang does not teach wherein the composition is formulated for subcutaneous or intramuscular administration.
However, Belyakov teaches a combination of cytidine-based antineoplastic drugs with cytidine deaminase inhibitors and use thereof in the treatment of cancer (title). Belyakov teaches gemcitabine is a cytidine-based antineoplastic drug that has been used in conjunction with CDA inhibitors (pg. 3, lines 20-23). Belyakov teaches both subcutaneous or intramuscular injections are known methods for administering compositions and in order to prolong the effect of a drug, it is desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. (pg. 44, lines 7-11, pg. 43, lines 20-21).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the method of Tang such that the composition is formulated for subcutaneous or intramuscular administration for the purpose of treating cancer in a subject as taught by Belyakov. A person of ordinary skill in the art would have had the motivation to do so as these are established routes of administration for delivering combination therapies combining gemcitabine and CDA inhibitors in order to treat the cancer. Formulation for subcutaneous or intramuscular administration would be within the technical grasp of the skilled artisan attempting to practice the invention.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Tang (Int. J. Pharmaceutics, 2021, IDS filed March 6, 2024, available online April 30, 2021) and Belyakov (WO 2010/118013, IDS filed March 6, 2024) as applied to claims 1-10, 12-13, 16-22, 24-25, and 27 above in view of Yang (Chemical Engineering Journal, 2020, cited on PTO-892).
Regarding claim 11: As discussed above, Tang and Belyakov render obvious a composition of microparticles using biodegradable polylactide-polyglycolide polymers.
They do not specify the specific polymers recited by instant claim 11.
However, Yang teaches the use of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers as a hydrogel depot for sustained administration of gemcitabine derivatives (abstract). Yang teaches it is known in the art to use drug-loaded in situ hydrogel depots comprising PLGA-PEG-PLGA for dispersing drugs (pg. 2, col. 1, last para.).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of Tang and Belyakov by using the PLGA polymer poly(D,L-lactic acid-co-glycolic acid) as taught by Yang in the microparticle depot formulation. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as Belyakov establishes polylactide-polyglycolide polymers are generally useful for this purpose in gemcitabine containing compositions, and Yang establishes that specifically PLGA polymer poly(D,L-lactic acid-co-glycolic acid) is a specific polymer used for this purpose.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Tang (Int. J. Pharmaceutics, 2021, IDS filed March 6, 2024, available online April 30, 2021) as applied to claims 1-6 and 16-22, 24-25 above in view of Schridde (US 2006/0154891, cited on PTO-892).
Regarding claims 14-15: As discussed above, Tang teaches the composition of claim 4.
Tang does not teach wherein the composition comprises benzyl alcohol as a preservative.
However, Schridde teaches pharmaceutical compositions in the form of ready-to-use preparations of gemcitabine in aqueous solutions in a glass containers having specified dimensional relationships demonstrate long shelf life over a wide range of solution pH values (abstract). Schridde teaches preferably benzyl alcohol is a preservative to be used in the composition (pg. 4, paras. 0055-0056).
Taken together it would have been prima facie obvious to modify the composition of Tang such that it includes benzyl alcohol as a preservative as suggested by Schridde. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success in order to improve the shelf life of the composition and benzyl alcohol is a known preservative in compositions comprising gemcitabine.
Conclusion
No claims are allowed in this action.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Talebian (J. Mater. Chem. B, 2020, cited on PTO-892) teaches biopolymer-based hydrogels comprising gemcitabine for cancer drug delivery (abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMUEL L GALSTER/Examiner, Art Unit 1693
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