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 .
DETAILED ACTION
Claims 1, 2, 5, 8-11, 13, 14, 16, 17, 24, 26, 27, 35, 36, 38, 40, 52 and 58 are currently pending in a preliminary amendment filed 10/04/2023.
Priority
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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/04/2023 was filed before the mailing date of the instant first action on the merits. The submission thereof is in compliance with the provisions of 37 CFR 1.97. It is noted that the foreign references have only been considered to the extent that an English language abstract, translation or statement of relevance has been provided to the examiner. Accordingly, the information disclosure statement has been considered by the examiner, and signed and initialed copy is enclosed herewith.
Claim Objection
Claims 13, 14 and 16 are objected to minor informalities.
Claim 13 recites “a triglyceride” in line 3 twice.
Each of claims 14 and 16 are not written in a proper Markush-type claim format where the Markush-type claim should recite alternatives in a format such as "selected or chosen from the group consisting of A, B, and C." Alternatively, the format “selected or chosen from A, B or C” can be used. (see MPEP 2111.03 –II and 2117 and MPEP 2173.05(h)).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 35, 36, 38, 40, 52, and 58 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating urinary infection with silver sulfadiazine (SSD) and/or cefpodoxime, does not reasonably provide enablement for any urinary system disorder treatment other than the urinary infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
“The factors to be considered in making an enablement rejection have been summarized as 1) the quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence or absence of working examples, 4) the nature of the invention, 5) the state of the prior art, 6) the relative skill of those in that art, and 7) the predictability or unpredictability of the art, and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546. Here, 1) Whether any urinary system disorder can be treated by an intravesical administration of any pharmaceutical agent would require extensive and potentially opened ended clinical research on subjects. 2) The specification does not provide sufficient amount of direction or guidance for treating any urinary system disorder and but just provides treatment of urinary tract infection using SSD and cefpodoxamine (see Examples 1-2). 3) There is no working example other than treating urinary infection in the specification. 4) Instant claim 35 define a method for treating any urinary system disorder comprising intravesical administration of a formulation comprised of microparticles having a mean diameter of 50nm-2000microns, pharmaceutical agent and carrier to a subject, and the microparticles are buoyant in urine, and the formulation is at least partially retained by the bladder for a duration of a drug delivery time period upon which the active agent is released. 5) The state of the art is that no general procedure is art-recognized for treating any urinary system disorder with an intravesical administration of any pharmaceutical agent. In particular, the attached American Cancer Society, “Treating Bladder Cancer”, 2025, pages 1-48 discloses that intravesical therapy is suitable for certain type of bladder cancer (e.g., non-muscle invasive bladder cancer) (page 15), while the intravesical therapy is not likely helpful for most stage II or higher muscle invasive bladder cancer (page 16). Thus, it cannot be ascertained that intravesical therapy is good for any urinary system disorder (e.g., muscle invasive bladder cancer). 6) The artisan prescribing Applicants invention would be a Board Certified urologist in taking care of intravesical therapy for treating urinary system disorder with any pharmaceutical agent with at least MD degree and several years of experience. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting any compound to be effective for e.g., the cancer treatment. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent menopause and its symptoms specified in the claims generally. 7) It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved", and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Therefore, the enablement requirement is not satisfied.
The remaining claims are also rejected due to the rejection of base claim 35.
Claims 1, 2, 5, 8-11, 13, 14, 16, 17, 24, 26, 27, 35, 36, 38, 40, 52 and 58 are
rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Each of claims 1 and 35 recites the term “pharmaceutically active agent” in line 4, and however, those claims are vague and indefinite because the term can be read on the reach-through claim. A functional definition of “pharmaceutically active agent” ("reach-through" claim) covers all compounds possessing pharmaceutical activity in those claims. It would be an undue burden to isolate and characterize all potential compounds, without any effective pointer to their identity or to test every known compound and every conceivable and undiscovered future compound for this activity to see if it falls within the scope of the claims. In effect, the applicant is attempting to patent what has not yet been invented. Thus, the Examiner recommends to put the specific names for the pharmaceutical agent in the claims.
Claim 52 recites “the controlled release” which lacks sufficient antecedent basis because base claim 35 recites “a controlled release carrier” instead of “a controlled release”.
Each of claims 5 and 40 depends from cancelled claims 4 and 40, respectively. No claim depends from a cancelled claim because it is not clear from which claim it is supposed to depend.
The remaining claims are also rejected due to the rejection of base claims 1 and 35.
Appropriate correction is requested.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5, 8-11, 13, 14, 17, 24, 26, 27, 35, 38, 40, 52 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., “Long-term floating control-released intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer”, Drug Development and Industrial Pharmacy, 2017, vol. 43, no. 8, pp. 1343-1350 (IDS of 10/04/2023) in view of Levisage et al. (US2003/0008015A1).
Applicant claims the below claims 1 and 35 filed on 10/04/2023:
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Determination of the scope and content of the prior art
(MPEP 2141.01)
Wang discloses treatment of bladder cancer comprising intravesical administering long-term preparations, e.g., mini-pellet preparations comprising 5-fluorouracil cancer drug which reads on the claimed chemotherapy active agent, and glyceryl tristearate (GTS) matrix which reads on the claimed controlled carrier matrix fatty acid ester, triglyceride, and the prepared long-term preparations could maintain an effective 5-fluorouracil concentration in the bladder for about one month, and furthermore, in this period the 5-fluorouracil concentration in blood was always far less than that in urine (abstract), and the pellet has a diameter of 2 mm (1344, left column, third paragraph: Preparation of mini-pellets); the mini-pellets contains 15%, 25% or 35% of 5-fluorouracil which is within the claimed range of 2.5 to 95% (Table 1 on page 1345). Although Wang does not expressly teach the amount of GTS matrix carrier, since Wang teaches the amount 15%, 25% or 35%of 5-fluorourasil, the relative amount of GTS would be determined without undue experimentation (instant claims 1 and 35 (in part), and instant claims 11, 13, 14, 17, 24, 26, 38 and 40); the 5-flurorourasil is released from the GTS (page 1345, right column, third paragraph) (instant claim 5), and the 5-fluorourasil is dispersed into the GTS matrix (page 1344, left column, third paragraph: Preparation of mini-pellets) (instant claim 8); and the GTS coats around 5-fluorouracil particles and thus, 5-fluorouracil could not directly dissolve into water under GTS coat (page 1345, right column, the last second paragraph) (instant claim 9); the GTS slowed down the invading rate of water into the mini-pellets, and with the slow erosion of the GTS, the hydrophilic 5-fluorouracil would gradually expose to water medium and be dissolved, and in mini-pellets, GTS formed a continuous phase and slowed down the releasing rate of 5-fluorouracil (page 1345, right column, second paragraph)(instant claim 10); and the preparations have the greatest local therapeutic effect and the smallest systemic drug side effects, and therefore, the GTS based 5-fluorouracil floating long-term control-released intravesical mini-preparation prepared in this study is an ideal preparation for the treatment of bladder cancer (page 1349, left column, last paragraph), and the mini-pellet is more suitable for the using in long-term sustained release purpose (page 1345, right column, third paragraph) (instant claims 24, 26 and 52); and the intravesical administration improves local drug efficacy and reduction of systemic side effects (page 1348, right column); and 1.5 g of 5-fluorouracil was administered which reads on unit dose and the amount is within the claimed range of 60 mg to 5g (instant claim 58). MPEP 2144.05: “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
However, Wang does not expressly teach microparticles of instant claims 1 and 35 and additional ingredients of instant claim 27. The deficiencies are cured by Levisage.
Levisage discloses polymer controlled delivery of a therapeutic agent (title) in the form of microparticles wherein microparticles has a polymeric support material preferable adapted disperse therapeutic agent and the polymer material comprises at least 50% homopolymer (abstract); the therapeutic agent includes 5-fluorouracil or paclitaxel as an anticancer agent for treating bladder cancer (claims 15-16 and 18 of prior art); the formulation comprises at least one encapsulated therapeutic agent dispersed within the microparticles ([0015] and [0021]-[0022]); and the therapeutic agent is encapsulated within microparticles for local delivery to a pre-determined target tissue ([0012]) and thus the anticancer drug e.g., paclitaxel can be successfully loaded into microparticles and then administered intravesically to mice with bladder cancer, the survival rate and body weight of mice were significantly higher for mice receiving such microparticle delivery vessels with encapsulated paclitaxel than for (control) mice treated with non-loaded microparticle delivery vessels or treated with free paclitaxel ([0013]); the used polymeric support materials include poly(methylidene malonate 2.1.2) and preferred additional polymer includes polyvinylalcohol, polyethyleneoxide, polyvinylpyrrolidone which reads on the claimed dispersant, , etc. ([0062] and [0079]) (instant claim 27); the microparticles release encapsulated therapeutic substances into the surrounding environment with a controlled rate of release, and they do not significantly inhibit biological activity of the encapsulated substance, and the microparticles provide controlled and localized delivery of the encapsulated agents to a targeted issue of a patient ([0043]) and the diameter of microparticle is in the range of 0.5 micron to 100 microns ([0044]) which is within the claimed range (instant claims 1 and 35, microparticles). See MPEP 2144.05 above. This prior art further teaches that the microparticles dosing was based on the total amount of drug encapsulated, not on the amount of drug actually released to the urothelium paclitaxel could be released from the particles and, as the particles remained adsorbed to the bladder mucosa for several days, this allowed a sustained delivery of the drug to the urothelium, and this implies that even if the paclitaxel dose available at one time was lower int the case of the particles, the drug remained close to the urothelium and active for several days, and this was better than in the case of the free paclitaxel, quickly eliminated in urine ([0114]).
It would have been obvious to modify the mini-pellets of Wang with microparticles having encapsulated therapeutic agent of Levisage for the same treatment of cancer, e.g., bladder cancer. One of the ordinary artisan would have been motivated to do so because microparticles drug delivery provides controlled and localized delivery of the encapsulated agents to a targeted tissue of a patient by releasing encapsulated agent into bladder in a controlled rate of release without significantly inhibiting biological activity of the encapsulated agent, as taught by Levisage. Further, it would have been obvious to add additional polymer dispersant of Levisage to the composition of Wang in order to enhance the release properties of the composition.
In light of the foregoing, instant claims 1, 5, 8-11, 13, 14, 17, 24, 26, 27, 35, 38, 40, 52 and 58 are obvious over Wang in view of Levisage.
Claims 2 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., “Long-term floating control-released intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer”, Drug Development and Industrial Pharmacy, 2017, vol. 43, no. 8, pp. 1343-1350 (IDS of 10/04/2023) in view of Levisage et al. (US2003/0008015A1) and further in view of Tsubaki et al (US2013/0011670A1).
However, Wang in view of Levisage does not expressly teach the gravity of instant claims 2 and 36. The deficiency is cured by Tsubaki
Tsubaki discloses microparticles (=fine particles) has a specific gravity of e.g., 0.1 to 1.8g/cm3, and if the specific gravity is smaller than 0.1g/cm3 which overlaps the instant range of less than 1.03, floating of the fine particles becomes large ([0056]-[0057]) (instant claims 2 and 36).
Although Want in view of Levisage does not expressly teach gravity of microparticles recited in instant claims 2 and 36, to be float in the urine, the particles should have gravity less than gravity (1.005 to 1.03) of urine as supported by the instant publication at [0071]. In this respect, Wang teaches mini-pellets’ floating in the urine where the floating property in intravesical drug delivery system is the significant prolongation of the drug’s residence time in bladder, leading to enhanced therapeutic efficacy while minimizing systemic side effects, and Levisage teaches microparticles of the same anticancer agent such as 5-FU for the same treatment. Therefore, it would have been prima facie obvious to modify the teachings of Wang in view of Levisage with specific range gravity of Tsubaki. One of the ordinary artisan would have been motivated to do so because the certain gravity of microparticles impacts on the floating properties and overlapping range of gravity makes the microparticles floating in the urine, as taught/suggested by Tsubaki.
In light of the foregoing, instant claims 2 and 36 are obvious over Wang in view of Levisage and further in view of Tsubaki.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., “Long-term floating control-released intravesical preparation of 5-fluorouracil for the local treatment of bladder cancer”, Drug Development and Industrial Pharmacy, 2017, vol. 43, no. 8, pp. 1343-1350 (IDS of 10/04/2023) in view of Levisage et al. (US2003/0008015A1) and further in view of Ashton et al. (US2003/0170286A1).
However, Wang in view of Levisage does not expressly teach surfactant of instant claim 16. The deficiency is cured by Ashton.
Ashton discloses treatment of genitourinary tract disorders comprising administering an active agent such as 5-FU ([0037]) as particles ([0051]), carrier, excipient, surfactant, dispersant, etc. ([0050] and claim 12 of prior art) for the treatment of cancer e.g., bladder cancer, wherein the surfactant includes sodium lauryl sulfate ([0236]).
It would have been obvious to further add surfactant such as SLS of Ashton to the composition of Wang in view Levisage in order to enhance the drug delivery, solubility and stability properties of the composition.
In light of the foregoing, instant claim 16 is obvious over Wang in view of Levisage and Ashton.
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, 2, 5, 8-11, 13, 14, 16, 17, 24, 26, 27, 35, 36, 38, 40, 52 and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-9, 17, 28, 29, 46, 48-61 of copending application no. 18/858722.
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets require a population of particles comprising an active agent and a carrier matrix in a controlled release manner over certain period of time for the treatment of urinary system disorder including cancer, overlapping amounts of agent and carrier, floating properties, various active agents, overlapping specific gravity of particles, and treating method using the population. The difference between them is that the claimed invention requires microparticles while claim 1 of copending ‘722 remains silent. However, a plurality of particles embraces the claimed microparticles. Thus, the claimed invention would be obvious from copending ‘722 application.
Conclusion
All examined claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYUNG S CHANG whose telephone number is (571)270-1392. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Yong (Brian-Yong) S Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYUNG S CHANG/Primary Examiner, Art Unit 1613