DETAILED ACTION
Status of Claims
The amendment submitted December 24, 2025 has been entered.
Claims 1, 10, and 16-20 are pending and under consideration.
Claim 14-15 were previously cancelled.
Claims 2-9 and 11-15 are cancelled.
Claims 1-6, 8-10, 13, 17, 19, and 20 were previously amended.
Claim 1 is currently amended.
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
This application is a 371 National Phase Application of PCT/EP2020/074494 filed September 2, 2020, which claims the benefit of priority to European Patent Application No. EP19020505.4, filed on September 3, 2019.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d), and the certified copy has been filed.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
In nonprovisional applications, applicants and other individuals substantively involved with the preparation and/or prosecution of the application have a duty to submit to the Office information which is material to patentability as defined in 37 CFR 1.56. The provisions of 37 CFR 1.97 and 37 CFR 1.98 provide a mechanism by which patent applicants may comply with the duty of disclosure provided in 37 CFR 1.56 using an IDS. The IDS may be filed using form PTO/SB/08. See MPEP § 609.
37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. The applicant is once more reminded of their legal obligation to submit to the Office information which is material to patentability.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 24, 2025 has been entered.
WITHDRAWN OBJECTIONS
The examiner withdraws objections under 35 U.S.C. 132(a) based on introduction of new matter based on Applicant not pursuing amendment to specification.
WITHDRAWN REJECTIONS
The examiner withdraws rejections to Claims 1, 10, and 16-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ) based on claim amendments and Applicant’s remarks.
The examiner withdraws rejections to claims 1-2, 5-11, 13, and 16-20 under 35 U.S.C. 112(b) based on amendments to the claims and Applicant’s remarks.
The examiner withdraws rejections to claim 1-2, 4-5, and 13 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Tanigawa et al (Tanigawa, Tetsuya, Rama Pai, Tetsuo Arakawa, and Andrzej S. Tarnawski. "Rebamipide inhibits gastric cancer cell growth." Digestive diseases and sciences 52 (2007): 240-247) (herein referred to as Tanigawa) based on claim amendments and cancellation of claims 2, 4-5, and 13.
The examiner withdraws rejections to claims 1 and 16-20 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Cho et al (USPN 11,420,963 B2) based on claim amendments by Applicant.
The examiner withdraws rejections to claims 1-3 and 10-12 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Murai et al. (Murai, R., T. Kanbe, T. Mukoyama, T. Shimomura, K. Hashiguchi, Y. Yoshida, H. Tsuchiya, Y. Hoshikawa, A. Kurimasa, and G. Shiota. "Effect of rectal administration of rebamipide on dextran sulfate sodium-induced colitis: role of hepatocyte growth factor." Inflammation Research 56 (2007): 240-245) based on claim amendments and cancellation of claims 2-3, and 10-11 by Applicant.
The examiner withdraws rejections to claims 1-2, 4, 6-7, 9, 16 and 18 as being anticipated by Yasuda et al. (Yasuda, Takashi, Hiroshige Chiba, Takafumi Satomi, Akira Matsuo, Tadayoshi Kaneko, Daichi Chikazu, and Hironobu Miyamatsu. "Preventive effect of rebamipide gargle on chemoradiotherpy-induced oral mucositis in patients with oral cancer: a pilot study." Journal of Oral & Maxillofacial Research 2, no. 4 (2012): e3.) based on claim amendments and cancellation of claims 2, 4, 6-7, 9 by Applicant.
The examiner withdraws rejections to claims 1, 6 and 8 under 35 USC 103 based on claim amendments and cancellation of claims 6 and 8 by Applicant.
Claim Interpretation
As defined by Applicant, “"Rebamipide", as used herein, shall include all forms of this active ingredient, such as the anhydrous form, hydrated or solvated form (e.g. hemihydrate form), crystalline forms; and pharmaceutically acceptable salts thereof (page 3, lines 10-14).
Consequently, using broadest reasonable interpretation, rebamipide is interpreted to additionally include all prodrugs of rebamipide.
The Examiner notes that despite Applicant’s remarks of changing the language to “rebamipide prodrugs”, claim 1 remains directed to rebamipide.
As defined by Applicant, “Cancer" as used herein is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. This invention relates specifically to cancers associated with increased intestinal permeability, a condition that enables passage of carcinogens present in the gastrointestinal tract into the body proper, thus contributing to development of malignancies. These carcinogens may trigger cancerous growth directly in the bowel and/or surrounding tissues but also in more distant organs and tissues. The underlying mechanism for this phenomena resides in the ability of carcinogens to spread via bloodstream even to remote parts of the body.”
As defined by Applicant, “Increased intestinal permeability" is used herein as a term designating little intestinal wall defects, including those caused by subclinical chronic inflammation (low grade inflammation) of the gut wall. These intestinal wall defects may be manifested e.g. by chronic constipation or gastroparesis. Increased intestinal permeability may be diagnosed using specific tests, such as lactulose-mannitol test (LAMA test; e.g., Sequeira J.R. et al. (2014) PLoS One; 9(6):e99256), A-1-AT test, or zonulin test. Typically, increased intestinal permeability is permeability of the intestinal wall to particles having the size of more than 4 Angstroms in radius.”
As defined by applicant, “The term “abuse" as used herein is meant to include any consumption, which is not necessary for medical reasons and leads to dependency and/or health impairments including low grade inflammation of the gut wall.”
As defined by applicant “Prophylaxis" or “prophylactic use" shall be understood herein as preventing or delaying the onset of the disease including its recurrence in patients with complete or partial remission, e.g. after surgical treatment, chemotherapy, radiation therapy, or immunotherapy. It is also intended to include preventing or delaying the progression of the disease. In such a case rebamipide is administered to a patient who is in an initial or early stage of the disease to be treated in order to prevent or delay its progression to the next stage. The prophylactic effect of rebamipide resides in its ability to prevent passage of carcinogenic substances and other toxins into the body proper, thereby preventing events triggering cancer initiation.”
As defined by Applicant, “Treatment" shall be understood herein as a therapy that is able to slow, stop, inhibit or reverse the disease. It is also meant to cover reduction or alleviation of clinical symptoms of the disease. “Slowing down" the disease means reducing its progress while not being able to completely stop or reverse it, whereas “stopping" the disease means being able to completely halt its progression.
NEW REJECTIONS
Applicant’s claim amendments have necessitated new grounds of rejection.
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.
Claims 1, 10, and 16-20 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.
Claim 1 is directed to “administering to the subject an effective amount of rebamipide or a pharmaceutically acceptable salt thereof excluding rebamipide.”
However, based on the current claim construction it is unclear what is being administered based on the exclusion of rebamipide and phrasing “a pharmaceutically acceptable salt thereof.”
The Examiner suggests amending claim 1 to be consistent with Applicant’s remarks and directed towards “excluding rebamipide prodrugs,” to remedy the ambiguity.
(Please note: for the purposes of examiner, the examiner is interpreting claim one to refer to “excluding rebamipide prodrugs.”).
Claims 10 and 16-20 are likewise rejected for failing to remedy the ambiguity.
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.
Claim 1, 10, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al (USPN 11,420,963 B2).
Regarding claim 1, Cho teaches “A method for preventing colon cancer in a human subject having increased intestinal permeability comprising administering to the subject an effective amount of rebamipide or a pharmaceutically acceptable salt thereof-, excluding rebamipide, wherein said administration reduces intestinal permeability (abstract). “
The Examiner notes that reducing intestinal permeability is an outcome resulting from administration of rebamipide.
Specifically, Cho teaches that “in addition to gastric ulcer, acute gastritis and chronic gastritis, rebamipide is known to have prophylactic and therapeutic effects on xerophthalmia, cancer, osteoarthritis, and rheumatoid arthritis (Column 1, last paragraph, lines 60-67).”
Cho also recites a method for treating a disease including cancer using rebamipide (column 146, claim 9 of Cho).
Regarding Claim 16, Cho teaches “wherein rebamipide is administered in an oral pharmaceutical form (column 18, paragraphs 2-3 at lines 12-28)
Regarding claim 17, Cho teaches “wherein the oral pharmaceutical form is a form with enteric release (column 18, paragraph 2 at lines 13-16).”
Specifically, Cho teaches that “the pharmaceutical composition of the present invention may be formulated into a preparation suitable for use in releasing the active ingredient in an immediate, sustained or delayed manner. The preparation may be in such a form as a powder, a granule, a tablet, an emulsion, a syrup, an aerosol, a soft or hard gelatin capsule, a sterile injection, or a sterile powder (column 18, paragraph 2 at lines 13-16).”
Regarding claim 18, Cho teaches “wherein the pharmaceutical form contains rebamipide and at least one pharmaceutically acceptable excipient (column 18, paragraph 1, lines 3-5).”
Specifically, Cho teaches “In addition, the pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable additive. The additive may be any one of a carrier, an excipient, and a diluent, as typified by lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. A filler, an anti-coagulant, a lubricant, a humectants, a flavoring agent, an emulsifier, and a preservative may be used in the pharmaceutical composition of the present invention (column 18, paragraph 1, lines 3-12).” Therefore, Cho teaches that the pharmaceutical additive may be a pharmaceutically acceptable excipient.
Regarding claims 19-20, Cho teaches “wherein rebamipide is administered in a daily dose of 1 to 5000 mg (column 17, lines 56-67).”
Specifically, Cho teaches “The pharmaceutically effective daily dosage is about 0.5 mg/kg body weight to 100 mg/kg body, and preferably about 1 mg/kg body weight to 30 mg/kg body weight of the rebamipide or its pharmaceutically acceptable salt thereof. However, the pharmaceutically effective dose may vary depending on various factors including the severity of disease, the patient's age, weight, health condition, and sex, the route of administration, and the time of administration (column 17, lines 56-67).
The only difference between instant invention and Cho is Cho’s invention pertains to rebamipide prodrugs.
Therefore, it would have been prima facie before the effective filing date of the claimed invention to modify Cho and access instant invention based on routine optimization because the only difference is the use of prodrugs compared to rebamipide alone.
A person of ordinary skill in the art would be motivated to modify Cho to investigate rebamipide instead of its prodrug as part of routine optimization in developing a treatment plan for colon cancer as a comparative example. It is well-known in the art that patient treatment is highly personalized.
Therefore, one would arrive at instant invention as a predictable result with a reasonable expectation of success.
Therefore, Claims 1, 10 and 16-20 are rejected as being obvious.
Conclusion
Claims 1, 10, and 16-20 are under consideration and remain rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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