DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the third Office action on the merits of the claims.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Continued Examination
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 17 August 2026 has been entered.
Status of the Claims
Applicant amended claim 2 and cancelled claims 12, 25-26, and 31-32. Claims 1, 3, 10, and 23 were cancelled previously by Applicant. Claims 2, 4-9, 11, 13-22, 24, and 27-30 are pending.
Status of the Rejections
The rejection of claims 2, 4-9, 11, 13-22, 24, and 27-30 under 35 U.S.C. 112(a) for lack of enablement is new.
The rejection of claim 32 under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s cancellation of the claim.
The rejection of claims 2, 4-9, 11, 13-22, and 27-30 under 35 U.S.C. 112(b) is new.
The rejection of claim 31 under 35 U.S.C. 112(d) is withdrawn in view of Applicant’s cancellation of the claim.
The rejection of claims 2, 4-9, 11-22, and 24-32 under 35 U.S.C. 103 as being unpatentable over Fellstrom (“Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial.” The Lancet 389.10084 (2017): 2117-2127) in view of Calliditas Therapeutics (“Pharmalink’s core patents for Nefecon® treatment for renal disease granted in United States, Europe, China and Hong Kong.” 2014 July 10. [Press Release]), Watts (US 8,491,932 B2), Villa (US 9,192,581 B2), and Gareb 2016 (“Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease.” European Journal of Pharmaceutics and Biopharmaceutics 103 (2016): 32-42) is withdrawn in view of Applicant’s combination of narrowing amendments to claim 2.
All three provisional rejections on the ground of non-statutory double patenting are withdrawn in view of Applicant’s combination of narrowing amendments to claim 2.
Claim Rejections - 35 U.S.C. 112(a)
The following is a quotation of 35 U.S.C. 112(a):
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.
Claims 2, 4-9, 11, 13-22, 24, and 27-30 are rejected under 35 U.S.C. 112(a) for lack of enablement.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics, 8 USPQ2d 1217 (Fed. Cir. 1988)). MPEP § 2164.01. Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. MPEP § 2164.01(a). These factors were outlined in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988) and include the following: (1) the breadth of the claims; (2) the nature of the invention; (3) the state of the prior art; (4) the level of one of ordinary skill; (5) the level of predictability in the art; (6) the amount of direction provided by the inventor; (7) the existence of any working examples; and (8) the quantity of experimentation necessary needed to practice the claimed invention based on the content of the disclosure. MPEP § 2164.01(a). These factors are addressed below.
The breadth of the claims. The independent claim (claim 2) is directed, in part, to an enterically-coated budesonide tablet. The core of the tablet comprises budesonide, a gelling matrix material (about 15-20 wt% of the total tablet), and a disintegrant (about 0.5-5 wt% of the total tablet). Claim 2 recites no limitation concerning the concentration of budesonide. Furthermore, the claim is generic regarding the enteric coating, the gelling matrix material, and the disintegrant. Claim 2 also includes a combination of four functional limitations concerning the release profile of the tablet, which serves as a proxy for targeting budesonide release to the ileum following oral administration. Klein, Sandra. “The use of biorelevant dissolution media to forecast the in vivo performance of a drug.” The AAPS Journal 12.3 (2010): 397-406. In the interest of clarity, the examiner notes that the ileum is the final and longest section of the small intestine, located between the jejunum and the large intestine. The functional limitations of claim 2 are narrow, whereas the compositional limitations of claim 2 are broad.
The nature of the invention. The claimed invention has considerable complexity because it is directed to the pharmaceutical and medical arts.
The state of the prior art. There is relevant art concerning ileum-targeting budesonide tablets, most notably: Gareb, Bahez, et al. “Development of a zero-order sustained-release tablet containing mesalazine and budesonide intended to treat the distal gastrointestinal tract in inflammatory bowel disease.” European Journal of Pharmaceutics and Biopharmaceutics 103 (2016): 32-42.” The guidance provided by Gareb focuses on a specific combination of pharmaceutical excipients at specific concentrations and is best encapsulated by Table 2 (page 34) reproduced below:
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The level of one of ordinary skill. In view of the breadth of the claims, the state of the art, the nature of the invention, and the state of the prior art, the level of ordinary skill is high, i.e., a person of ordinary skill in the art typically has a Ph.D. in pharmaceutics, pharmacology, chemical/biomedical engineering, or a closely-related scientific discipline, as well as several years of relevant work experience.
The level of predictability in the art. The field of pharmaceutical formulations development is unpredictable.
The amount of direction provided by the inventors. The direction provided by the inventors concerning the composition of a budesonide tablet that targets budesonide release to the ileum is generic, aside from the working examples. See, e.g., Specification at p. 48 (“Such tablet compositions of the invention may be gelling matrix tablets that further comprise a gelling matrix material, such as a low molecular weight HPMC.”). In other words, the working examples, themselves, constitute the only meaningful guidance on formulating a budesonide tablet that targets release to the ileum.
The existence of any working examples. Example 24 (page 91), reproduced below, is the most relevant of the three exemplary tablet formulations.
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The specification states: “The budesonide release from these tablets matches the dissolution profile required to achieve the majority of release to the ileum. What is particularly surprising that the combination of a gelling agent (hypromellose) with a disintegrant (crospovidone) allowed the achievement of the correct in vitro dissolution profile. Although it is expected that other tablet formulations are possible to achieve the desired release profile.” Page 93 at para. [0464]. The examiner notes that Example 24 utilizes crospovidone and the following mixture of gelling agents: Hypromellose 100 mPa·s and Hypromellose 4000 mPa·s. None of Applicant’s claims recites the foregoing combination of three excipients or even approximates it. The two remaining tablet formulations, i.e., Example 22 (pages 88-89) and Example 23 (pages 90-91) are merely prophetic in relation to ileum release.
The quantity of experimentation. “Oral drug products with a drug release in the ileum are challenging to develop,” as evidenced by Blümlinger, Michael, et al. “Illeum targeted semaglutide delivery and pharmacokinetic study in an experimental porcine animal model via oesophagogastroduodenoscopic administration.” Journal of Controlled Release (2025): 114164. “This is due to two main factors: (1) the achievement of the actual drug release in the ileum and (2) the in vivo measurement of the location of the drug release in an adequate animal model.” Blümlinger at page 2, left column. Similarly, “several features of the gastrointestinal tract pose unique challenges to successful drug delivery,” as evidenced by Chu JN, Traverso G. “Foundations of gastrointestinal-based drug delivery and future developments.” Nat Rev Gastroenterol Hepatol. 2022 Apr;19(4):219-238 PMID: 34785786. On page 5, Chu further evidences:
The gastrointestinal tract has a large absorptive surface with a total surface area of ~250–400 m2 and is subdivided into several anatomic compartments: the oesophagus, stomach, small intestine and colon. The compartments of the gastrointestinal tract differ in many properties, including length and absorptive area, drug residence and transit time, pH, mucus thickness, cell types and transporters, permeability, and bacterial diversity and population (Table 1). These diverse properties pose a challenge for drug delivery systems, but also provide opportunities for targeted drug delivery by exploiting the differences between compartments.
Given the nature of the claimed invention and the limited number of relevant working examples, among the other observations made above, very significant and lengthy experimentation would have to be undertaken before a person having ordinary skill in the art could practice Applicant’s claimed invention. Considerable laboratory experimentation would be required to identify those gelling matrix material, disintegrant, and enteric coating combinations — as generically defined in the claims — that focus release of budesonide in the ileum, in accordance with the four functional limitations recited in claim 2. MPEP § 2164.08(b) (“Although, typically, inoperative embodiments are excluded by language in a claim (e.g., preamble), the scope of the claim may still not be enabled where undue experimentation is involved in determining those embodiments that are operable.”).
On the basis of the foregoing factors and observations, the examiner concludes that a person having ordinary skill in the art could not practice Applicant’s invention, as claimed, without first engaging in undue experimentation.
Claim Rejections - 35 U.S.C. 112(b)
The following is a quotation of 35 U.S.C. 112(b):
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.
Claim 2, 4-9, 11, 13-22, and 27-30 rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter that the inventor regards as the invention.
Claim 2 recites the following limitation: “a gelling matrix material.” Given the limited guidance provided by the specification of the present application, persons having ordinary skill in the art can reasonably disagree over which pharmaceutical excipients other than hydroxypropyl methylcellulose (HPMC) qualify as a gelling matrix material. See, e.g., Specification, page 48 at para. [0253] (“Such tablet compositions of the invention may be gelling matrix tablets that further comprise a gelling matrix material, such as a low molecular weight HPMC (e.g., Hypromellose).”). Therefore, claim 2 and all claims depending thereon (except claim 24) are indefinite. MPEP § 2173.04 (“a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim)”).
Conclusion
Claims 2, 4-9, 11, 13-22, 24, and 27-30 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER ANTHOPOLOS whose telephone number is 571-270-5989. The examiner can normally be reached on Monday – Friday (9:00 am – 5:00 pm). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany P. Barham, can be reached on Monday – Friday (9:00 am – 5:00 pm) at 571-272-6175. The fax number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.A./
29 September 2026
/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
