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, filed 08/07/2023 is a National Stage entry of PCT/EP2022/053030, International Filing Date: 02/08/2022. PCT/EP2022/053030 Claims Priority from Provisional Application 63147060, filed 02/08/2021.
Status of Claims
Claims 1-40, 42, and 44 are currently pending as of the claim set filed on 8/7/23. Claims 41, 43, and 45-50 have been canceled.
Claims 1-40, 42, and 44 were examined. Claims 1-40 and 42 are rejected. Claim 44 is objected to.
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.
Claim(s) 1-40 and 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glicklich et. al., WO 2016112075 A1, publ. 7/14/2016, in view of Danese et. al., J. of Crohn’s and Colitis, publ. 2018, pp. S678-S686.
Glicklich teaches methods of treatment of sphingosine-1-phosphate subtype 1 (S1P1) receptor associated disorders by administering the compound (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid, also referred to as compound 1 or APD334, wherein S1P1 receptor associated disorders include inflammatory bowel disease and ulcerative colitis (title & abstract; p. 1, lines 4-22). Glicklich further teaches the methods encompass the use of compounds having agonist activity at the S1P1 receptor, with selectivity over the S1P3 receptor, as S1P1 selective agonists exhibit no or substantially no bradycardia side effect (p. 34, lines 16-27). Glicklich teaches inflammatory bowel diseases to be treated include mild, moderately active, and severely active ulcerative colitis, wherein treatment results in clinical remission (p. 9, lines 11-18; p. 15, line 17-p. 16, line 18). Glicklich teaches a dosing regimen wherein three or more doses of compound 1 are administered in a step-down or de-escalation regimen, with the first dose being greater than the second dose, and the third dose being less than the second (p. 16, line 38-p. 17, line 13). Glicklich teaches another embodiment wherein the doses are administered once daily, and wherein the administered doses are sufficient to induce desensitization of the heart such that no acute heart rate reduction occurs (p. 16, lines 23-27). Glicklich teaches additional embodiments wherein the first period of time for administration of a dose is up to two weeks, e.g., from 3 days to no more than two weeks; additionally, the first period of time can comprise multiple subperiods (p. 21, lines 27-38). An embodiment of treating ulcerative colitis by administering an amount of Compound 1 from about 0.5 to 2.5 mg. is taught (p. 54, lines 8-12); additionally, doses as low as 0.1 mg. are taught (p. 18, line 3-p. 21, line 24). Glicklich teaches an embodiment wherein the individual to be treated has demonstrated an inadequate response to, loss of response to, or intolerance to another therapeutic such as 5-aminosalicylates, corticosteroids, immunosuppressives, TNFalpha antagonists, and integrin antagonists (p. 37, lines 19-26).
Glicklich doesn’t explicitly teach or suggest amiselimod as claimed.
Danese teaches ulcerative colitis and Crohn’s disease as chronic and relapsing-remitting inflammatory bowel diseases, and while conventional management of these conditions involves treatment with glucocorticoids, 5-aminosalicylic acid, biologics, and immunomodulators, there is currently no curative therapy (p. S678, 1st para). Additionally, a third of IBD patients don’t respond to conventional therapy, while another third of patients show a loss of response over time, necessitating new therapeutic options (p. S678, 1st-2nd para). Danese teaches S1P as a pleiotropic lipid mediator, having a dual role in inflammatory response; S1P1 is the most widely represented S1P receptor subtype, being expressed mostly on endothelial cells and lymphocytes (p. S679, 1st -3rd para under The S1P pathway). Danese teaches amiselimod (MT-1303), along with APD334 as selective S1P1 modulators under evaluation for Crohn’s disease, and despite being as potent as another S1P modulator, fingolimod, amiselimod causes lower rates of adverse events (p. S681, Table 2; p. S682, left col., 1st -3rd full para). Notably, amiselimod doesn’t exert activity on the S1P3 receptor subtype (p. S682, Fig. 2).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the method of treating or ameliorating ulcerative colitis in a subject in need thereof, comprising: administering a first dose of amiselimod during a first administration period; and administering a second dose of amiselimod during a second administration period, wherein the first dose is larger than the second dose, in view of the combined teachings of Glicklich and Danese. Glicklich teaches a method of treating inflammatory bowel disease, including mild, moderate, or severely active ulcerative colitis by administering the selective S1P1 modulator, APD334; administration of daily doses, and in a dose step-down or de-escalation regimen is further exemplified, wherein the first dose administered for a time period is greater than the second and third doses administered. Danese teaches both ADP334 and amiselimod as selective S1P1 modulators, and that amiselimod appears to be associated with lower rates of adverse events and improved patient safety. As such, one of ordinary skill in the art would have been motivated to have treated a subject for ulcerative colitis by administering the selective S1P1 modulator, amiselimod, as S1P1 modulation is taught to be a therapeutic strategy for ulcerative colitis, with the reasonable expectation that fewer side effects, e.g., negative chronotropic effects such as bradycardia would have resulted. As Glicklich teaches a step-down dose regimen as a therapeutic strategy, wherein a first dose administered for a first time period of up to two weeks is greater than a second dose and optionally third dose administered thereafter, one of ordinary skill in the art would have been motivated to have adapted this regimen to the treatment of ulcerative colitis, and have had a reasonable expectation of success. Glicklich teaches a dose range from about 0.1 mg. to about 2.5 mg.; therefore, it would have been prima facie obvious to have arrived at a first dose within this range, and a second dose within this range, wherein the first dose is greater than the second dose, such as by 2 or 2.5 times larger, in consideration of the guidance provided by Glicklich. As Glicklich teaches the timeline for the first dose to be up to two weeks, it would have been prima facie obvious to have administered the first dose of amiselimod to treat ulcerative colitis for a first period of up to 14 days, thereby overlapping with the first administration periods recited by instant claims 10-12. Regarding instant claim 13, although the second administration period of at least one year is not explicitly taught, Danese teaches ulcerative colitis as a chronic disease without a cure. Therefore, it would have been prima facie obvious that treatment with the S1P1 modulator, amiselimod, for ulcerative colitis would have been chronic, and that the drug would need to be administered indefinitely, e.g., the second administration period of at least one year.
Regarding instant claim 14, Danese teaches conventional management of ulcerative colitis or Crohn’s disease involves treatment with glucocorticoids, 5-aminosalicylic acid, biologics, and immunomodulators, while Glicklich teaches treating an individual having had an inadequate response to, loss of response to, or intolerance to another therapeutic. Therefore, it would have been prima facie obvious to have incorporated administration of amiselimod to a subject having ulcerative colitis, who is undergoing treatment with another therapy such as those mentioned above, that they have demonstrated an inadequate response to.
Regarding instant claim 15, Danese teaches S1P1 agonists/modulators to exert anti-inflammatory effects and selectively block the egress of effector T cells from secondary lymphoid tissue to gastric mucosa (p. S681, para before Clinical study; pp. S683-S684, bridging 1st para of Conclusions). Danese also provides examples wherein S1P1 modulation reduced pro-inflammatory cytokines (p. S680, see Table 1). Therefore, it would have been prima facie obvious to one of ordinary skill in the art administration of the S1P1 modulator, amiselimod, to a subject in need of treatment for ulcerative colitis would have reduced inflammation in the subject’s GI tract.
Claim Objection
Claim 44 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Information Disclosure Statements
The IDS filed on 8/7/23, 10/30/24, and 1/29/26 have been considered.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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, Kortney Klinkel can be reached at 571-270-5239. 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.
SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627