DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ claimed invention, filed 31 January 2025, in the matter of Application N° 19/042,930. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The originally filed claims are at issue. No additions, amendments, or cancellations have been made. The issue of new matter is moot.
Thus, claims 1-20 represent all claims currently under consideration.
Information Disclosure Statement
One Information Disclosure Statement (IDS) filed 31 January 2025 is acknowledged and has been considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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. Applicants are 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 1-3, 6, 9-12, 15, 16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Shanmugam et al. (USPN 11,523,993 B1; IDS reference).
The instantly claimed invention is directed to a tablet comprising:
an effective amount of at least one of: tafamidis, a pharmaceutically acceptable salt thereof (i.e., meglumine), and a tafamidis co-crystal;
at least one solubilizing agent selected from cyclodextrin, substituted cyclodextrin derivatives, and mixtures thereof; and
at least one excipient selected from a diluent, a disintegrant, and a lubricant.
Claim 20 recites a method of treating a transthyretin amyloid disease in mammals, comprising administering a therapeutically effective amount of the tablet of claim 1.
Shanmugam discloses a tablet comprising 61 mg of tafamidis or 20 mg of tafamidis meglumine and at least one pharmaceutically acceptable excipient (see e.g., claim 1). The excipient is further disclosed as being a disintegrant, diluent, lubricant, or mixture thereof (see e.g., claim 4). The practiced composition is further taught as containing a solubility enhancer, which is defined further still as being selected from α-, β-, and γ-cyclodextrins and derivatives thereof (see col. 6, lines 4-11). The limitations directed to the amount of solubilizing agent recited by instant claims 2 and 9 are also met by the reference (see col. 6, lines 12-27).
Disclosure of cyclodextrin and/or its derivatives is additionally considered to meet the recited dissolution property of instant claim 15. See MPEP §2111.01(IV) and §2112.01(I).
The recited amount of lubricant of instant claim 10 is read on by claim 21 of the reference.
The recited amount of diluent of instant claim 11 is read on by claims 14-17 of the reference.
The recited amount of disintegrant of instant claim 12 is read on by claim 21 of the reference.
The limitations recited by instant claim 16 are also disclosed by the foregoing disclosure for the solubilizing agent, whereby carbohydrates are read on by povidone, copovidone, PEG, and sorbitol monooleate polysorbate (see col. 6, lines 4-11).
Lastly, the instantly recited method is disclosed (see e.g., Abstract; claim 29).
Based on the teachings of the reference, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Claims 1-3, 6-12, 15, 16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Shanmugam et al. (US Pre-Grant Publication Nº 2023/0149365 A1).
The limitations of claims 1-3, 6, 9-12, 15, 16, and 20 are discussed above.
The limitations of claims 7 and 8 are directed to tafamidis co-crystal form, such as tafamidis fumaric acid.
Shanmugam discloses a tablet comprising tafamidis (e.g., 61 mg), tafamidis meglumine (e.g., 20 mg), or tafamidis free acid fumaric acid cocrystal and at least one pharmaceutically acceptable excipient for the purposes of treating transthyretin-mediated amyloidosis (see e.g., Abstract; claims). The excipient is further disclosed as being a disintegrant, diluent, lubricant, or mixture thereof. See e.g., ¶[0012]. The practiced composition is further taught as containing a solubility enhancer, which is defined further still as being selected from α-, β-, and γ-cyclodextrins and derivatives thereof, as well as povidone, copovidone, PEG, and sorbitol monooleate polysorbate (see e.g., claim 22 and ¶[0061]), thereby meeting the solubilizer limitations recited by claims 1 and 16. The limitations directed to the amount of solubilizing agent recited by instant claims 2 and 9 are also met by the reference. See ¶[0062].
Disclosure of cyclodextrin and/or its derivatives is additionally considered to meet the recited dissolution property of instant claim 15. See MPEP §2111.01(IV) and §2112.01(I).
The recited amount of lubricant of instant claim 10 is read on by ¶[0066] of the reference.
The recited amount of diluent of instant claim 11 is read on by ¶[0060] of the reference.
The recited amount of disintegrant of instant claim 12 is read on by ¶[0056] of the reference.
Based on the teachings of the reference, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Claims 1-3 and 5-20 are rejected under 35 U.S.C. 103 as being unpatentable over Shanmugam et al. (US Pre-Grant Publication Nº 2023/0149366 A1; IDS reference) in view of Das et al. (WO 2022/185333 A1).
The limitations of claims 1-3, 6-12, 15, 16, and 20 are discussed above.
The limitations of claims 5 and recite that the effective amount of tafamidis is about 12.2 mg/tablet and 61 mg/tablet, respectively.
The limitations of claim 17 recite that the tafamidis has a D90 particle size of about 20 microns or less. This limitation also appears in independent claims 18 and 19.
Claim 18 additionally comprises a solubilizing agent (e.g., cyclodextrins) and at least one excipient selected from a diluent, disintegrant, and lubricant; and wherein the composition is “essentially free of” (i.e., has less than 5 wt%) acidifiers.
Claim 19 recites a tablet composition comprising tafamidis having a D90 particle size of about 20 microns or less; a cyclodextrin or derivative thereof, an inorganic ionic compound; and a carbohydrate.
Shanmugam discloses a solid oral dosage form comprising:
tafamidis or a pharmaceutically acceptable salt or its solid-state forms or polymorphic forms thereof;
at least one acidifier in an amount of about 0% w/w to about 10% w/w based on the total weight of the dosage form; and
at least one pharmaceutically acceptable excipient (see e.g., claim 1; Abstract).
Claim 2 discloses that the solid oral dosage form may be a tablet.
Claims 4 and 5 disclose the limitations of instant claims 3, 5, and 6, respectively.
The one or more excipients of claim 1 are further defined as being selected from: diluents, disintegrants, and lubricants (see e.g., claim 9). The amount of diluent present in the practiced tablets is further defined by claims 15 and 16, and ¶[0062], thereby reading on instant claims 1 and 11.
Claim 13 discloses further defines the excipient as being a lubricant in an amount that reads on the instantly recited range of claim 10. See also ¶[0068].
Claim 10 discloses further defines the excipient as being a disintegrant in an amount that reads on the instantly recited range of claim 12. See also ¶[0059].
Paragraph [0063] discloses that the composition may comprise at least one solubility enhancer, and that examples of such enhancers include, but are not limited to, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and derivatives thereof. Additional compounds that define the combination of solubility enhancers that may used include such carbohydrates as povidone, copovidone, polyethylene glycol, and sorbitol monooleate polysorbate. The solubility enhancer is taught as being present in the practiced composition in amounts that read on the range recited by instant claims 1, 2, and 9. See ¶[0064].
Claim 19 discloses that pharmaceutically active salt or its solid-state forms or polymorphic forms has a D90 particle size ranging from about 20 to about 100 microns. Paragraph [0097] additionally teaches that the lower the particle size of tafamidis or its pharmaceutically acceptable salts or its solid-state forms (e.g., D90 less than about 15 microns), these particles will exhibit fast release during administration. Solid state formulations containing particles having a D90 less than about 15 microns are taught as releasing tafamidis faster than the reference product. The foregoing disclosure is considered to teach the structural particle size limitations of claims 17-19, but also teach and suggest the release limitations recited by instant claim 14.
The limitations of claim 14 are considered to be met by the dissolution profiles of the various Examples disclosed throughout. The Examiner acknowledges that
The limitations of claim 15 are met by the disclosure of claim 8. See also ¶[0105]-¶[0106]. Of particular note is that the practiced dosage form (including the solubility enhancer) is soluble in an aqueous medium having a volume of about 900 mL.
The limitations of claims 7 and 8 are additionally considered to be met by the disclosure of tafamidis in a solid-state or polymorphic form comprising tafamidis and fumaric acid (see e.g., Abstract).
Regarding the recited composition of claim 18, the Examiner submits that the foregoing disclosure accounts for each of the recited tafamidis active, particle size distribution, solubilizing agent(s), and excipients. Furthermore, claim 1, for instance, is noted as teaching that the acidifier component may be present in an amount of 0% (i.e., optional), thereby meeting the claimed “essentially free” limitation.
The Examiner additionally observes that the reference defines the “acidifier” as being inclusive of inorganic acids. See e.g., ¶[0054].
The foregoing disclosure is also considered to teach the limitations of independent claim 19.
Lastly, the limitations of independent method claim 20 are considered to be met; the practiced compositions are directly disclosed as being used to treat transthyretin amyloid disease in mammals (see e.g., Abstract; claim 21).
Where the teachings of Shanmugam are deficient is with respect to the limitations of claim 13, whereby the tablet formulation comprises an outer film coating.
Das is considered to bridge this gap in teaching disclosing formulations comprising tafamidis (e.g., co-crystalline forms), methods for treating transthyretin-mediated amyloidosis in patients in need thereof (see e.g., Abstract; claims 21 and 23). Claim 24 further defines the administered formulations as including tablets and film-coated tablets.
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success at producing the instantly claimed composition and arriving at the recited method of treatment.
Regarding the added teachings of Das, the Examiner advances that a person of ordinary skill in the pharmaceutical arts would be motivated to modify Shanmugam’s tablet disclosure with a film coating in order to alter the release profile (i.e., target, slow, delay, etc.) of the tafamidis encapsulated therein.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Allowable Subject Matter
Claim 4 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.
The subject matter recited therein requires that tafamidis of claim 1 is narrowed to tafamidis meglumine and that a single tablet contains 80 mg.
The attached DailyMed entry for tafamidis meglumine is considered to represent a contribution to the closest art available to the instantly claimed invention. Therein, the art recognizes that 20 mg tablets containing tafamidis meglumine are administered and may be done so four times daily to total 80 mg per day. However, the state of the art does not teach a single 80-mg tablet. The DailyMed entry acknowledges that doses exceeding 80-mg (in capsule form) have been administered successfully (e.g., 160 mg and 480 mg). However, mixed side effects were reported. See Sections 2.1 Recommended Dosage and 10 Overdosage.
All remaining claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
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