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 .
Receipt is acknowledged of IDS filed on 11/06/2025.
Claims 49-50 have been added.
Claims 21 and 23 have been amended.
Claims 21, 23, 27-31, 34, 37-41, 44 and 49-50 are pending.
Claims 1-20, 22, 24-26, 32-33, 35-36, 42-43 and 45-48 are cancelled.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Foreign Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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.
Claims 27, 31, 37, 41, and 49-50 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 claims 27 and 37, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 27 recites the broad recitation "phosphate buffer solution", and the claim also recites (pH 7.4)" which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In the instant case, the parenthesis render it unclear if a pH of 7.4 is a preferred embodiment or a limitation.
Regarding claims 31, 41 and 49-50, the spacer represented by formula (I) in the instant claims, is H2N-(CH2)p-X. For the nitrogen to bond, it needs to become an active group by removing one of the hydrogens, since nitrogen can only have 3 bonds in total. 5 bonds on the nitrogen would be unstable. For compact prosecution purposes, the spacer is interpreted to be HN-(CH2)p-X.
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.
Claims 21, 23, 27-31, 34, 37-41 and 44 and 49-50 are rejected under 35 U.S.C. 103 as being taught by NARITA (US 2017/0354675 A1) in view of MIYAMOTO (US 2016/0151506 A1).
Regarding claim 21 and 23, NARITA teaches a method of administering a chondroitin sulfate conjugated to a steroid (claim 1), which reads on, a hydrophobic compound and a pharmaceutical active ingredient, to a subject through a catheter (paragraph 0087) into the bladder (paragraph 0089), which reads on administering the compound to the lumen of the bladder, the steroid is gradually released in the urinary bladder (paragraph 0089), which reads on a sustained manner.
The molecular weight of chondroitin sulfate is 10,000 to 40,000 (Paragraph 0048). The molecular weight of the steroid is 360.4 to 434.5 (table 1). These values read on the molecular weight of the chondroitin sulfate is 10 times or more the molecular weight of the pharmaceutically active ingredient.
The composition includes specific chondroitin sulfate derivatives, such as 21-( β-alanyl)-triamcinolone acetonide (table 2). According to Applicant’s specification, 21-( β-alanyl)-triamcinolone acetonide has a clogP value of 2.17. Therefor this reads on the limitation of a ClogP of 1 or more.
Regarding claim 27 and 37, NARITA teaches the steroid is gradually released in the urinary bladder (paragraph 0089). The steroid release rate is preferably 0.1 %/day to 4%/day in a 10 mM phosphate buffer solution of pH 7.4 and 36° C (paragraph 0064).
Regarding claim 28-30 and 38-40, NARITA teaches the chondroitin sulfate and spacer are covalently bonded through an amide bond and the spacer and steroid are covalently bonded through an ester bond (paragraph 0053).
Regarding claim 31 and 41, NARITA teaches the spacer is represented by the following formula: -HN-(CH2)m-CHR1-CO-, wherein m can be 1 (claim 1), the spacer further has a carboxyl group (paragraph 0053). The spacer represented by formula (I) in the instant claims, is H2N-(CH2)p-X. For the nitrogen to bond, it needs to become an active group by removing one of the hydrogens, since nitrogen can only have 3 bonds in total. 5 bonds on the nitrogen would be unstable.
Regarding claims 34 and 44, NARITA teaches the molecular weight of the steroid is 360.4 to 434.5 (table 1).
Regarding claims 49 and 50, NARITA teaches the steroid is gradually released in the urinary bladder (paragraph 0089). The steroid release rate is preferably 0.1 %/day to 4%/day in a 10 mM phosphate buffer solution of pH 7.4 and 36° C (paragraph 0064). NARITA teaches the chondroitin sulfate and spacer are covalently bonded through an amide bond and the spacer and steroid are covalently bonded through an ester bond (paragraph 0053). NARITA teaches the spacer is represented by the following formula: -HN-(CH2)m-CHR1-CO-, wherein m can be 1 (claim 1), the spacer further has a carboxyl group (paragraph 0053). The spacer represented by formula (I) in the instant claims, is H2N-(CH2)p-X. For the nitrogen to bond, it needs to become an active group by removing one of the hydrogens, since nitrogen can only have 3 bonds in total. 5 bonds on the nitrogen would be unstable. NARITA teaches the molecular weight of the steroid is 360.4 to 434.5 (table 1).
The composition is for an anti-inflammatory effect and uses a steroid, such as prednisolone (page 3, paragraph 0050).
NARITA does not teach using a pharmaceutical active ingredient that is not a steroid.
MIYAMOTO teaches a chondroitin sulfate bonded to a physiologically active substance in the form of an anti-inflammatory agent, such as the steroid prednisolone (page 5, paragraph 0092) or a nonsteroidal anti-inflammatory drug (claim 1, 3 and 4), such as diclofenac (Page 5, paragraph 0093) which is a hydrophobic compound. The chondroitin sulfate and spacer are covalently bonded through an amide bond (claim 6) and the nonsteroidal anti-inflammatory drug and spacer are covalently bonded through an ester bond (claim 5). The physiologically active substance is released as the bond between the substance and the spacer decomposes (claim 1). The disassociation rate of the substance from the chondroitin sulfate in a phosphate buffer at a pH of 7.5 at 36C is 0.3 to 5%/day (Page 10, paragraph 0163).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate a nonsteroidal anti-inflammatory drug, such as diclofenac. The person of ordinary skill in the art would have been motivated to make those modifications, because diclofenac and prednisolone are functional equivalents of anti-inflammatory pharmaceuticals and reasonably would have expected success because both compositions are created in almost identical ways, including the ester and amide bonds between the active ingredient, spacer and chondroitin sulfate, as well as the gradual release rate of MIYAMOTO is within the range of NARITA.
Note, with regard to claim 21 and 23, the wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). This is in regards to “wherein the delivery of the pharmaceutical active ingredient to the submucosal tissue of the bladder is facilitated by binding the hydrophobic compound containing the pharmaceutical active ingredient to chondroitin sulfate as compared with a case where the pharmaceutical active ingredient itself is administered as a single agent”, especially since the prior art teaches the same composition and administration method.
Response to Arguments
Applicant argues, that one skilled in the art would recognize that NARITA is an invention premised on the use of steroids and the suppression of side effects of those steroids. Therefore, combining/modifying NARITA, which presupposes the use of steroids, with an API other than a steroid defeats the gist of NARITA's invention.
This is not found persuasive because, NARITA teaches the steroid was combined with the composition due to wanting to prevent adverse side effects due to the steroid releasing too fast, the primary goal of the composition, a spacer and chondroitin sulfate, was to lower the release rate which would in turn lower the adverse side effects (page 6, paragraph 0099). The purpose of combining the steroid or anti-inflammatory agent in MIYAMOTO with the composition, a spacer and chondroitin sulfate, is also to control the release rate at a speed that allows the drug to function properly and treat the desired disorder (page 1, paragraph 0008-0009). Both references solved the release rate problem using a spacer and chondroitin sulfate combined with the drug, a steroid or an anti-inflammatory agent, and both resulted in the same rate of release. The disassociation rate of the substance from the chondroitin sulfate in a phosphate buffer at a pH of 7.5 at 36C is 0.3 to 5%/day (Page 10, paragraph 0163) in MIYAMOTO, which is within the range of NARITA which is 0.1 %/day to 4%/day in a 10 mM phosphate buffer solution of pH 7.4 and 36° C (paragraph 0064). Furthermore, MIYAMOTO teaches that both prednisolone, which is taught in NARITA, and diclofenac, the non-steroid anti-inflammatory agent can be used in the composition.
Applicant argues, although NARITA describes the intravesical administration and prodrug action of CS-steroids, NARITA does not describe or fairly suggest the delivery of active pharmaceutical ingredients to the submucosal tissue of the bladder (i.e., the delivery of active pharmaceutical ingredients to the submucosal tissue by passing them through the bladder mucosa).
This is not found persuasive because Applicant’s specification states the method of administration for submucosal tissue of the bladder comprises, “A method in which a urethral catheter is inserted into the lumen of the bladder under aseptic conditions to evacuate residual urine, and thereafter, the chondroitin sulfate derivative is injected through the same catheter” (Applicant’s specification page 25, paragraph 2).
NARITA teaches, an example of a method used to administer the agent for treating bladder diseases consists of inserting a urinary catheter into the urinary bladder under aseptic conditions and discharging any residual urine followed by injecting the agent for treating bladder diseases through the same catheter (page 5, paragraph 0088).
That is NARITA teaches the exact administration method used in Applicant’s specification and NARITA and MIYAMOTO together teach the same pharmaceutical composition as in the instant claims, so it would be inherent that the composition would be administered to the same part of the bladder, such as the submucosal tissue.
Applicant argues, Furthermore, the claimed invention is characterized in that "binding the chondroitin sulfate improves submucosal delivery and permeability." The applied references, even if taken in combination, do not describe or fairly suggest that binding the chondroitin sulfate improves permeability, and a person skilled in the art would not have any reasonable expectation of achieving this feature. In addition, even assuming arguendo that the Office Action has somehow set forth a primafacie case of obviousness with respect to any of the claims (as amended), the patentability of the claims is further supported by unexpected results and advantages. Because such effects ( e.g., the unexpected effect of improving the delivery of active pharmaceutical ingredients to the submucosal tissue) could not have been reliably predicted on the basis of the teachings of the applied references, the results achieved by the claimed features are surprising and unexpected (to one of ordinary skill in the art).
This argument is not persuasive because the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Furthermore, unexpected results must be supported by factual evidence, and attorney argument is not evidence. See In re Pearson, 494 F.2d 1399,1405 (CCPA 1974). The cited paragraphs of the Specification detail benefits of the claimed method but do not state that unexpected results were obtained. Thus, Applicant has not provided evidence that unexpectedly superior results were obtained with the claimed method. "Mere improvement in properties does not always suffice to show unexpected results." In re Soni, 54 F.3d 746,751 (Fed. Cir. 1995).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL HARTLEY can be reached at (571) 272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.L.M./Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618