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 .
Summary
Claims 1-15, 17, 18, 23, 25-27, 30, 34, 37 and 38 are pending in this office action. Claims 16, 19-22, 24, 28-29, 31-33 and 35-36 are cancelled. All pending claims are under examination in this application.
Priority
The current application filed on March 22, 2023 is a 371 of PCT/US2023/068009 filed June 6, 2023, which in turn claims domestic priority to a provisional patent application 63/349,470 filed on June 6, 2022.
Information Disclosure Statement
Receipt of the Information Disclosure Statement filed on February 3, 2026 is acknowledged. A signed copy of the form PTO/SB/08 is attached to this office action.
Claim Rejections - 35 USC § 112(a), Written Description
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 27, 30 and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, Paragraph 1, “Written Description” Requirement, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. This should include the following considerations: (1) actual reduction to practice, (2) disclosure of drawings or structural chemical formulas, (3) sufficient relevant identifying characteristics such as complete structure, partial structure, physical and/or chemical properties and functional characteristics when coupled with a known or disclosed correlation between function and structure, (4) method of making the claimed invention, (5) level of skill and knowledge in the art and (6) predictability of the art. For each claim drawn to a single embodiment or species, each of these factors is to be considered with regard to that embodiment or species. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention. Where skill and knowledge in the art is high adequate written description would require fewer species to be disclosed than in an art where little is known; further, more species would need to be disclosed to provide adequate written description for a highly variable genus.
First, what do the claims as a whole cover? Claim 27 is directed to a pharmaceutical composition comprising ebselen with a particular disintegration time and dissolution rate. Claims 30 and 34 are directed to a method of delivering ebselen to achieve particular Cmax values.
Second, how does the scope of the claims compare to the scope of the disclosure? The disclosure contains the same language found in the claims in the rejection; there is no disclosure of any disintegration time or dissolution rate. Table 3 shows some Cmax results for two specific compositions.
Third, the factors need to be considered.
(1) What was actually reduced to practice?
Formulations 1 and 2 were actually reduced to practice.
(2) Is there disclosure of drawings or structural chemical formulas?
The structural chemical formula is given for ebselen; the compound itself does not lack written description. The drawing shows percent of drug released over time for the two specific formulations.
(3) Are there sufficient relevant identifying characteristics disclosed?
There are no characteristics disclosed that result in the clamed disintegration times or dissolution rates or the claimed Cmax values. The specification teaches many possibilities for the filler, disintegrant, lubricant and glidant but contains no discussion of how to choose any of them to achieve the claimed disintegration times or dissolution rates or the claimed Cmax values. Amounts of ingredients are disclosed and claimed but, again, no correlation is presented between the amounts of ingredients and the clamed disintegration times or dissolution rates or the claimed Cmax values.
(4) Is there at least one method of making the claimed invention disclosed?
A dosage form formulator would have no difficulty making the compositions for use in the methods; only basic formulation skills would be needed.
(5) What is the level of skill in the art and what knowledge is present in the art?
The level of skill in the art of dosage form design is high, about that of a PhD pharmacologist with several years’ experience. The level of skill needed to actually make the formulations is less high, that of a formulation technician.
\(6) What is the level of predictability of the art?
The level of predictability of achievement of particular disintegration times or dissolution rates or the Cmax values is low since, until the dosage form is created and tested, there is no information upon which to base a prediction of what disintegration times or dissolution rates or Cmax values might be obtained, except for the two formulations tested.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not demonstrate that applicant was in possession of the claimed invention.
Claim Rejections - 35 USC § 112(b)
Claim 27 is 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 27 is directed to a pharmaceutical composition comprising ebselen with a particular disintegration time and dissolution rate. There is nothing specifically recited in the claim that would be expected to give this result. It would be expected that the claimed composition would have A dissolution rate, for example, but it is not clear which ingredients and/or which proportions would result in the specific values claimed.
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.
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 1-15, 17, 18, 27, 30, 34 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Kil et al., WO 2006096759 A2, published September 14, 2006 in view of Holmgren et al., US Patent No. 7,671,211 B1 published March 2, 2010.
Holmgren et al. is the US equivalent to the reference cited as D1 in the Written Opinion, used because the WO is in Japanese and the US patent is in English.
Kil et al. teach, at page 15, line 27 – page 16, line 18, a composition comprising ebselen or ebselen and allopurinol for oral use that can be obtained through combination of ebselen with solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable additional compounds, if desired, to obtain tablets or dragee cores. Suitable excipients are carbohydrate or protein fillers that include, among others, cellulose such as methylcellulose, hydroxypropylmethyl cellulose, or sodium carboxymethylcellulose (also known as croscarmellose sodium). If desired, disintegrating agents may be added, although croscarmellose sodium, known as a disintegrant, is already present in the composition.
Compositions comprising ebselen, which can be used orally, can be formulated, for example, as push-fit capsules that can comprise lubricants such as talc or magnesium stearate.
Kil et al. do not teach the claimed amounts of ingredients, although they do state, at page 17, lines 11-15, “The amounts of ebselen and allopurinol actually administered will be dependent upon the individual to which treatment is to be applied, and will preferably be an optimized amount such that the desired effect is achieved without significant side effects. The determination of an effective dose is well within the capability of those skilled in the art.”
Holmgren et al. teach, as stated in the Written Opinion, a tablet formulation containing 41% ebselen (compound A) (active compound), 20% carboxymethylcellulose (binder), 4% starch (glidant/ disintegrant), 33% crystalline cellulose (filler) and 1.6% magnesium stearate (lubricant) (example 1).
It would have been obvious to one of ordinary skill in the art, prior to the instant effective filing date, to formulate ebselen in a dosage form as claimed because Kil et al. and Holmgren et al. teach the claimed ingredients in similar amoutns for just that purpose. The amount of ebselen to dose is well within the ordinary level of skill in the art, as taught by Kil et al. and the amounts of excipients such as filler, disintegrant, lubricant and glidant are also well within the ordinary level of skill in the art, particularly since there is no evidence of criticality of said amounts.
Claims 23, 25, 26 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Kil et al., WO 2006096759 A2, published September 14, 2006 in view of Holmgren et al., US Patent No. 7,671,211 B1 published March 2, 2010. as applied to claims 1-18, 27, 30, 34 and 37 above, and further in view of Hrakovsky et al. US 20080008752 A1, published January 10, 2008.
The teachings of Kil et al. and Holmgren et al. are outlined above. They do not teach the distribution of ingredients between the intra-granlar phase and the extra-granylar phase.
Hrakovsky et al. US 20080008752 A1, published 2008-01-10 teach dosage forms containing memantine that are produced by a process comprising granulating memantine and at least one pharmaceutically acceptable excipient, preferably a diluent, a binder, and a disintegrant, in a liquid to form a granulate. The granulate is then preferably dried and milled. The granulate is then preferably used to form a composition that, for example, may then be compressed into tablet cores or filled into capsules, such as by blending with one or more pharmaceutically acceptable excipients, preferably a disintegrant, a glidant, and a lubricant.
Example 5 teaches dry granulation in paragraph [0049] Memantine hydrochloride (5 mg/tablet), lactose monohydrate (35 mg/tablet), povidone (1 mg/tablet), croscarmellose sodium (7 mg/tablet), and magnesium stearate (0.5 mg/tablet) [Part I] are blended to form a mixture. The mixture is then compacted or slugged, and then milled to form granules. The resulting granules are then blended with croscarmellose sodium (2 mg/tablet), microcrystalline cellulose (32.5 mg/tablet), and colloidal silicon dioxide (1 mg/tablet) [Part II] and magnesium stearate (1 mg/tablet) [Part III] to form the composition.
Notably, they mix memantine with filler, disintegrant and lubricant, dry-granulate that and then add glidant and lubricant and mix.
It would have been obvious to one of ordinary skill in the art, prior to the instant effective filing date, to follow the same process with the ebselen of Kil et al. and Holmgren et al. with the expectation of achieving useful dosage forms, just like Hrakovsky et al.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert A. Wax whose telephone number is (571)272-0623. The examiner can normally be reached 8:00 AM -4:00 PM Monday - Friday.
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, Jennifer Michener can be reached at (571) 272-1424. 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.
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
Prosecution Insights