Detailed Action
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 14 November 2025 has been entered.
Status of the Claims
The amendment filed 14 November 2025 (referred to herein as Remarks) is acknowledged. Claims 5 and 6 were cancelled. Claims 2, 4, 7, and 8 are currently pending.
Withdrawn Rejections
In view of Applicant amending the claims to recite wherein the riboflavin and TNFα inhibitor are in a single composition the 35 USC 102 rejection over Matsumoto is hereby withdrawn.
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 2, 4, 7, and 8 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 2 is drawn to “active ingredients” in lines 2 and 7 for use in “treatment of inflammatory bowel disease (IBD), Crohn’s disease, or other inflammatory conditions” in the las two lines. The scope of the composition is unclear. For example, is a composition comprising riboflavin, at least one TNF inhibitor, and a third agent (X) wherein the composition is useful for the treatment of multiple sclerosis (i.e., “other inflammatory condition”) and Crohn’s Disease; however, X is not an active ingredient in treating one condition while being active in treating the other disease within the scope of claim 2. To put another does the claim exclude ingredients that are active in treating any of the recited conditions, or alternatively, is an agent that is inactive for one of the claimed conditions within the scope. Further still Applicant in their Remarks assert amino acids and carbohydrates would be considered “active” agents and are therefore excluded from the claim while the specification teaches these same structures are auxiliary agents which are inactive and thus permissible (see Remarks pg. 6; see specification pg. 10 lines 19-26, pg. 11 lines 16-20). Therefore, the scope of the claimed composition cannot be ascertained.
The FDA defines “active” ingredient as “any component that provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or animals” (see Drugs@FDA pg. 1, accessed online 17 July 2025). Applicant points to a similar definition provided by the FDA (see Remarks pg. 4, 2nd para). It is noted Applicant has not provided a copy of the reference definition nor disclosed said reference in an information disclosure statement (IDS).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7 and 8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 7 is drawn to wherein the composition is for use as a medicament while the independent claim is wherein the composition is for use in the treatment of particular conditions. Therefore claim 7 expands the scope of claim 2 to include conditions not recited in claim 2.
Claim 8 is drawn to the composition of claim 2 for use in the treatment diseases identical to those recited in claim 2. Therefore, claim 8 does not further limit claim 2.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 2, 4, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over WO2018/112240 (referred to herein as Jones) and WO2014/070014 (referred to herein as Harmsen, as cited on the IDS received 08/02/2021).
Jones discloses a device for the release of a TNFα inhibitor into the gastrointestinal tract in order to treat disease. Jones specifically claims/discloses a method of treating gastrointestinal disease by administering a pharmaceutical formulation comprising a TNFα inhibitor that is released at a location in the gastrointestinal tract proximate to one or more sites of disease (see Jones claim 1, pg. 2 lines 15-16, pg. 3 line 29). Jones claims/discloses the TNFα inhibitor are identical to those instantly claimed (see Jones claims 113 and 137-141, para spanning pgs. 4-5, pg. 77 lines 8-10, pg. 25 lines 26-30) and treating both Crohn’s disease and inflammatory bowel disease (see Jones claims 48 and 50). Jones discloses the state of the art is such that infliximab and adalimumab are currently used in the treatment of Crohn’s disease (see Jones pg. 27 lines 26-28); thereby providing motivation to use these particular TNFα inhibitors. Symptoms of Crohn’s disease include frequent bowel motions, malnutrition, and dehydration with disruption in the activities of daily living (see Jones specification pg. 28 lines 20-23). Jones demonstrates using a colitis mouse and porcine models that administration of adalimumab via a cecal catheter/intra rectal was therapeutically effective (see Jones, experiment 1, pg. 282, lines 11-19, example 2b, pg. 284 lines 6-17, pg. 300 lines 24-30). Specifically, localized administration had less of a suppressive effect on the systemic immune response of an animal which is advantageous for treating pro-inflammatory disorders of the intestine (see Jones pg. 292 lines 20-24). Swine treated locally with adalimumab showed greater reduction in TNFα levels compared to systemic administration at the localized site (see figures 53 and 54, pg. 303 lines 1-6, 17-23). Jones also teaches,
“the formulation herein may also contain more than one active compound as necessary for the particular indication being treated, for example, those with complementary activities that do not adversely affect each other... Such molecules are suitably present in combination in amounts that are effective for the purpose intended” (see Jones pg. 25 lines 12-16).
Harmsen discloses using riboflavin, riboflavin phosphate or a salt thereof for supporting the growth or maintenance of oxygen sensitive bacteria in the gastrointestinal tract of an animal (see Harmsen abstract). Faecaliumbacterium prausnitzii (F. prausnitzii) has anti-inflammatory effects in cellular and TNBS colitis models and is one of the most abundant human colon bacteria (see Harmsen pg. 1 lines 20-24. Reduction in F. prausnitzii bacteria is associated with higher risk of postoperative recurrence of ileal Crohn’s Disease (see Harmsen pg. 1 lines 25-26). Volunteers receiving daily riboflavin had beneficial effects on F. prausnitzii population while not adversely affecting other bacterial populations (see Harmsen pg. 13 lines 3-19). Harmsen claims/discloses a pharmaceutical composition comprising riboflavin for use in treating inflammatory gastrointestinal disease in particular Crohn’s disease (see Harmsen claims 1 and 3, pg. 2 lines 1-3). Harmsen teaches using the composition in veterinary care and liquid formulations (see Harmsen pg. 4 lines 8-11). Harmsen also discloses a method for the selective stimulation of F. prausnitzii bacteria in the gastrointestinal tract in an animal comprising administering to the animal riboflavin, riboflavin phosphate or a physiologically acceptable salt thereof in order to selectively stimulate the growth of F. prausnitzii in the gastrointestinal tract (see Harmsen pg. 5 lines 16-21).
Therefore, the ordinary artisan would combine the formulation comprising adalimumab in a method of treating Crohn’s disease as taught by Jones with a second active agent riboflavin as taught by Harmsen. There is a reasonable expectation of success give Jones demonstrates localized release of adalimumab was able to treat colitis in animal models without adverse systemic side effects and Harmsen discloses riboflavin treatment increases F. prausnitzii bacteria (i.e., increasing anti-inflammatory activities) which is beneficial for Crohn’s patients. Jones teaches a second active agent in the formulation. Both Jones and Harmsen either reduce to practice the use in animals (i.e., mice, swine, humans) as well as the targeted area to be treated as the gastrointestinal tract.
Request for Interview
It is noted Applicant has requested an interview following the mailing of the office action (see Remarks pg. 8, 1st full para). Examiner is available for said interview. Please contact Examiner Petrash using the information provided below.
Conclusion
No claim allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HILARY ANN PETRASH whose telephone number is (703)756-4630. The examiner can normally be reached Monday-Friday 8:30-4:30 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, Misook Yu can be reached at (571)-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H.A.P./ Examiner, Art Unit 1644
/AMY E JUEDES/ Primary Examiner, Art Unit 1644
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