DETAILED ACTION
This office action is in response to applicant’s filing dated March 28, 2026.
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 .
Status of Claims
Claims 1-23 and 27 are pending in the instant application. Acknowledgement is made of applicant’s remarks filed March 28, 2026. Claims 24-26 and 28 were previously cancelled.
Election/Restrictions
Applicant’s election without traverse of LFA-1 antagonist (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4- tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid and the inflammatory bowel condition of ulcerative colitis in the reply filed on March 28, 2026 is acknowledged.
Claims 1-17, 23, and 27 are read on the elected species.
Claims 18-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 19, 2025.
Claims 1-17, 23, and 27 are presently under examination as they relate to the elected species of (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4- tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid and of ulcerative colitis.
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.
Claims 1-17, 23, and 27 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 one or more symptoms of an ulcerative colitis comprising administering the LFA-1 antagonist inhibitors (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6- carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid, (S,E)-2-(2,6-dichloro-4-((3 -(furan-2-yl)acrylamido)methyl)benzamido)-3 -(3- (methylsulfonyl)phenyl)propanoic acid, (S)-2-(5,7-dichloro-2-(3-hydroxybenzoyl)-1,2,3,4-tetrahydroisoquinoline-6- carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid, (2S)-2-(2,6-dichloro-4-(3 -hydroxy-3 -(3 -hydroxyphenyl)propyl)benzamido)-3 -(3- (methylsulfonyl)phenyl)propanoic acid, or (2S)-2-(2,6-dichloro-4-(3 -hydroxy-3 -(3 -hydroxyphenyl)propyl)benzamido)-3 - (thiophene-2-carboxamido)propanoic acid in the instant claims, does not reasonably provide enablement for a method of treating or preventing one or more symptoms of an inflammatory bowel disease. 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. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
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 the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to a method of treating, preventing, or ameliorating one or more symptoms of an inflammatory bowel disease in a subject.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As noted in claim 1, where all subsequent claims derive their dependence, the invention is drawn to generic symptoms of a generic inflammatory bowel disease. Developing therapies for the differing inflammatory bowel diseases and different symptoms is extremely unpredictable. As illustrative of treating, preventing, or alleviating the inflammatory bowel disease, the examiner cites Appiah et al. (U, Appiah, J. K. “Emerging Therapies in Inflammatory Bowel Disease: A Comprehensive Review” Journal of Clinical Medicine. (2025) pp. 1-12). For instance, according to Appiah et al., cited here for evidentiary purposes, Crohn’s Disease and Ulcerative Colitis are caused by differing biological pathways despite both being forms of Inflammatory Bowel Diseases (pp. 3, Figure 1). The compatibility and effectiveness of drugs depends on the type of Inflammatory Bowel Disease, for instance Anti-IL 17 Biologics specifically target Crohn’s Disease and not Ulcerative Colitis (pp. 12, Table 3). Furthermore, prior art in Inflammatory Bowel Diseases do not teach any method which can predictably bar a subject from acquiring a generic Inflammatory Bowel Disease or one of its symptoms. As such, it would be extremely unpredictable to determine whether a particular drug would be effective against a generic Inflammatory Bowel Disease or be capable of treating or preventing its onset.
Furthermore, as noted in the specification, there are numerous different symptoms associated with inflammatory bowel diseases such as abdominal cramping, abdominal pain, bloody stools, diarrhea, fatigue, fever, gas and bloating, loss of appetite, nausea and vomiting, rectal bleeding, upset stomach, and weight loss. Although all symptoms are caused by an inflammatory bowel disease, the different diseases have different etiologies and are drawn to differing patient populations.
As illustrative of treating, preventing, or alleviating the inflammatory bowel disease symptom of diarrhea, the examiner cites Cunha (V, Cunha, J. P. “Diarrhea” EMedicineHealth, (2026) pp. 1-13). For instance, Cunha, cited here for evidentiary purposes, teaches that diarrhea is one of the most common diseases which affects all age groups and patient populations (pp. 3, paragraph 2). Cunha also teaches that there are innumerable causes of diarrhea ranging from adverse reactions to food or medications, to viruses and bacteria, to intestinal diseases and disorders (pp. 4, paragraph 1 – pp. 8, paragraph 3). Although Cunha teaches of some medications which can slow down intestinal movement and stop some diarrhea symptoms, Cunha does not teach of any pharmaceutical which can predictably prevent or bar a subject from having diarrhea (pp. 13, paragraphs 2-6).
As illustrative of treating, preventing, or alleviating the inflammatory bowel disease symptom of abdominal pain, the examiner cites McMillen (W, McMillen, M. “Abdominal Pain: What You Should Know” WebMD (2024) pp. 1-6). McMillen, cited here for evidentiary purposes, teaches that abdominal pain is an extremely common and broad symptom with potential causes ranging from bacterial and viral infections, food intolerances, pregnancy, numerous types of different cancers, heart attacks, and gastrointestinal conditions (pp. 1, paragraph 1; pp. 1, paragraph 8 – pp. 5, paragraph 1). Although McMillen teaches that some medications can treat inflammation, acid reflux, ulcers, or infection, McMillen does not teach of any pharmaceutical which can predictably prevent or bar a subject from having diarrhea (pp. 6, paragraph 2). Furthermore, there are no known treatments which can prevent or bar a subject from acquiring the different inflammatory bowel disease symptoms.
These articles plainly demonstrate that the art of treating, preventing, and ameliorating a generic inflammatory bowel disease or its generic symptoms with a pharmaceutical drug is extremely unpredictable. Even if a compound can treat one such inflammatory bowel disease or one such symptom, it can not be predictably determined if the compound can treat, prevent, or ameliorate any type of inflammatory bowel diseases and any of its associated symptoms.
2. The breadth of the claims
Claims 1-17 and 27 are very broad in the potential diseases and symptoms being treated, prevented, or ameliorated. Although claim 23 is directed to a specific disease, it still encompasses generic symptoms of ulcerative colitis.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification teaches Example 1, wherein (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4- tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid was injected in a dose of 5 mg/kg to rats with oxazolone-induced acute colitis, a known model of ulcerative colitis. The compound induced less body weight deviation, lower DAI scores (indicating normal fecal properties and less fecal occult blood), lower colon weights, greater colon lengths, and lower colon densities than the vehicle (indicating less instances of distorted colon crypt structure, colon lymphocyte infiltration, colon muscle fibrosis, colon Goblet Cell loss, or colon crypt abscess). However, the specification does not teach of the compound treating generic inflammatory bowel diseases or all types of potential symptoms, or prevent or bar a subject from having any particular inflammatory bowel disease symptom. Thus, the working example does not provide sufficient written description support for the full scope of the claims.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4- tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid could predictably treat any inflammatory bowel disease other than ulcerative colitis and any symptom other than body weight decrease, fecal occult blood, abnormal fecal properties, distorted colon crypt structure, colon lymphocyte infiltration, colon muscle fibrosis, colon Goblet Cell loss, or colon crypt abscess. The skilled artisan would also not accept that (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4- tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid could predictably prevent or ameliorate any inflammatory bowel disease or symptom thereof.
Determining if any of the claimed compounds will treat any particular symptom would require formulation into a dosage form, and subjecting into clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of claims 1-17, 23, and 27 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Claim Rejections - 35 USC § 102
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 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- 17, 23, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burnier et al (US8367701 B2).
Regarding claims 1-17 and 23, Burnier teaches of a method of treating inflammatory bowel disease, including ulcerative colitis, comprising administering to a subject in need the amorphous or crystalline forms A, B, C, D, or E of formula 1 ((S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4- tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoic acid) (Column 43, paragraph 6; which reads on claims 1-5; 23). Where crystalline form A of formula 1 has an X-ray powder diffractogram comprising peaks at two-theta angles of approximately 18.2, 21.4, and 22.7 degrees and a thermogram comprising an endothermic peak at about 145 C (Column 2, Paragraph 2; which reads on the limitations of claims 1-9). Where crystalline form B of formula 1 has an X-ray powder diffractogram comprising peaks at two-theta angles of approximately 12.1, 17.1, and 18.5 degrees (Column 2, Paragraph 3; which reads on claims 1-6; 10-11). Where crystalline form C of formula 1 has an X-ray powder diffractogram comprising peaks at two-theta angles of approximately 4.8, 17.8, and 21.5 degrees (Column 2, Paragraph 4; which reads on claims 1-6; 12-13). Where crystalline form D of formula 1 has an X-ray powder diffractogram comprising peaks at two-theta angles of approximately 17.6, 21.7, and 24.8 degrees (Column 2, Paragraph 5; which reads on claims 1-6, 14-15). Where crystalline form E of formula 1 has an X-ray powder diffractogram comprising peaks at two-theta angles of approximately 5.12, 8.26, and 17.8 degrees (Column 2, Paragraph 6; which reads on claims 1-6; 16-17).
Thus, Burnier anticipates the method of claims 1-17 and 23.
Regarding claim 27, Burnier teaches that the daily dose of the amorphous form or any of the crystalline Forms A, B, C, D, or E, or a combination of Formula 1 is about 100 mg and 500 mg (Column 52, paragraph 6). Assuming the average weight of an adult human is 70 kg, an amount of 100 mg and 500 mg would be equivalent to 1.42 mg/kg (100 mg/ 70 kg = 1.42 mg/kg) and 7.14 mg/kg (500 mg/ 70 kg = 7.14 mg/kg) respectively. MPEP 2144.05 states: 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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Thus, Burnier anticipates the method of claim 27.
Conclusion
Claims 1-17, 23, and 27 are rejected.
No claim is allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON RAFANAN ULLMAN whose telephone number is (571)272-6623. The examiner can normally be reached 7:30 am to 5:00 pm M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AARON RAFANAN ULLMAN/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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