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 .
Application Status
Claims 1-15 were previously pending.
By virtue of Applicant’s preliminary amendment, filed 04 October 2024, claims 3, 5-7, and 9-15 were amended. No new claims were added and no claims were cancelled.
Therefore, claims 1-15 remain pending and under examination.
Priority
Acknowledgement is made for the following priority:
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Information Disclosure Statement (IDS)
The IDS (1) filed on 04 October 2024 has been considered by the examiner. A signed copy is enclosed.
Applicant is reminded of their duty to disclose to the Office all information known to the person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section.”
Claim Objections
Claims 3, 5, and 9 are objected to:
Claim 3 is objected to as reciting: “[t]he orodispersible tablet according to any of claims 1.” This is assumed to be a typographical error. Appropriate correction is required.
The phrase ‘of from’ is generally discouraged in US Patent claims. Several of the instant claims contain this claim language. Claim 5, however, is specifically objected to for reciting the ratio “…preferably of from to…” The extra ‘to’ renders the clause facially malformed.
Claim 9 is objected to because the recited list lacks a conjunction before the final surfactant. For proper grammatical form and clarity, applicant is required to insert ‘and’ or ‘or’ as appropriate before “sorbitan monolaurate.’
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 2-6, 8, 10, and 12 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.
Regarding claims 2, 4, 5, 8, 10, and 12, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 3 and 4 either directly (claim 3) or indirectly (claim 4) depend from claim 1. Claims 3 and 4 both recite “the first pharmaceutically acceptable disintegrant.” There is insufficient antecedent basis for this limitation because claim 1 does not recite a first pharmaceutically acceptable disintegrant.
Claim 6, which directly depends from claim 1, recites “…wherein any pharmaceutically acceptable disintegrant present in the orodispersible tablet is selected from…” It is unclear if this limitation further limits claim 1 as claim 1 recites a single disintegrant. If this was meant to limit claim 1, Applicant should reference already recited limitations by ‘the’ not ‘any’ (see USPTO’s claim drafting guidance: https://www.uspto.gov/sites/default/files/documents/Claim%20drafting.pdf Therefore, it is unclear). Since it is unclear whether this limitation refers to the disintegrant of claim 1 or adds an additional disintegrant, one of ordinary skill could not reasonably determine the metes and bounds of the claim.
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.
Claim 15 is 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 15 recites “[t]he orodispersible tablet according to claim 1 for use in the treatment of: a) prevention of…” The intended utility does not serve to further limit the orodispersible tablet of claim 1.
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
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.
Claims 1 and 3-12, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Tyebji (US PGPub. No. 2017/0000799 A1, published 05 January 2017) as evidenced by Lu (“Influence of Colloidal Silicon Dioxide on Gel Strength, Robustness, and Adhesive Properties of Diclofenac Gel Formulation for Topical Application,” published 11 December 2014); as evidenced by NEJM (“Oral rivaroxaban for symptomatic venous thromboembolism,” published 23 December 2010).
Tyebji discloses solid particles of a poorly soluble drug, pharmaceutical compositions comprising them, and processes for their preparation (abstract).
Regarding claim 1, Tyebji discloses:
The poorly soluble drug is selected from Xa inhibitors such as rivaroxaban ([0031]);
With an average particle size less than 100µm, whereby at least 90% of the weight of the particles have a particle size below 100µm ([0033]);
At least one pharmaceutically acceptable excipient that includes fillers, binders, disintegrants, lubricants, and/or combinations thereof ([0047]); and
The composition can be in the form of an orodispersible tablet ([0061]).
Furthermore, Tyebji provides an example of a direct compression procedure whereby pre-sieved rivaroxaban, sodium lauryl sulphate, lactose monohydrate, and hydroxypropyl methylcellulose are mixed, combined with microcrystalline cellulose and croscarmellose sodium, lubricated with magnesium stearate, and compressed into tablets ([0078]-[0084]).
Therefore, Tyebji discloses embodiments of the invention which include an orodispersible tablet comprising rivaroxaban particles have a D(v,90) of less than or equal to 100µm, a pharmaceutically acceptable disintegrant, and additional pharmaceutically acceptable excipients. The limitation that the tablet is “obtainable by a direct compression process” is product-by-process language. Although a product-by-process claim is defined by the recited process, patentability is determined based on the product itself (see MPEP 2113). Whereas here, when the prior art tablet is identical or substantially identical to the claimed tablet, the claim is obvious even if the reference does not disclose the tablet was prepared by the recited direct compression process. The burden therefore shifts to the applicant to establish the recited direct compression process imparts a structural or functional difference to the claimed tablet relative to the tablet disclosed by Tyebji (see MPEP 2113(II)).
Regarding claim 3, Tyebji discloses:
Useful disintegrants for the invention which include starches, polyvinylpyrrolidones, crosslinked carboxymethyl cellulose, ion exchange resins, low substituted hydroxypropyl cellulose or a combination thereof ([0052]). Therefore, Tyebji contemplates multiple disintegrants in the formulation.
Regarding claim 4, Tyebji discloses:
The preferred percentage of disintegrant in the formulation is between 0.1% to 20% by weight with respect to the total weight of the dry matter of the formulation ([0053]). This range encompasses the instantly claimed range (see MPEP 2144).
Regarding claim 5, Tyebji discloses:
A working example of a direct compression tablet containing 11.76% w/w and 3.53% w/w croscarmellose sodium (disintegrant) ([0078], Example 1). This simplifies to approximately 1 : 0.03002 rivaroxaban : disintegrant, thus falling within the instantly claimed range (see MPEP 2144).
Regarding claim 6, Tyebji discloses:
Useful disintegrants for the invention which include crosslinked carboxymethyl cellulose such as croscarmellose sodium ([0052]).
Regarding claim 7, Tyebji discloses:
Other additional suitable components to the formulation include binders and those binders are present from about 0.1% to 30% by weight with respect to the total weight of the dry matter of the formulation ([0050]-[0051]). This range encompasses the instantly claimed range (see MPEP 2144).
Regarding claim 8, Tyebji discloses:
Binders suitable for use in the invention include modified celluloses such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methylcellulose, and ethyl cellulose ([0050]).
Regarding claim 9, Tyebji discloses:
Surfactants suitable for use in the invention include sodium lauryl sulfate, polysorbate 20, polysorbate 40, polysorbate 60, and polysorbate 80 ([0038]).
Regarding claim 10, Tyebji discloses:
Lubricants suitable for use in the invention include colloidal silicon dioxide ([0053]-[0054]). Although Tyebji characterizes colloidal silicon dioxide as a lubricant, colloidal silicon dioxide was well known in the pharmaceutical arts to function as a glidant by improving powder flow in tableting (e.g., Lu at p. 636). Accordingly, the silicon dioxide expressly present in Tyebji’s tablet is capable of performing the claimed glidant function, and the reference’s alternate characterization of the ingredient does not structurally distinguish the claimed composition.
Regarding claim 11, Tyebji discloses:
Fillers suitable for use in the invention include mannitol and microcrystalline cellulose ([0048]). Tyebji’s direct compression tablet examples include microcrystalline cellulose ([0078]-[0094]). Applicant’s specification indicates the most preferred diluents of Applicant’s invention are mannitol and microcrystalline cellulose (p. 12, lines 12-18). A filler is also conventionally referred to in the pharmaceutical arts as a diluent because it increases the bulk of the dosage form. Accordingly, the disclosed microcrystalline cellulose satisfies the claimed diluent limitation, notwithstanding that Tyebji characterizes the material as a filler.
Regarding claim 12, Tyebji discloses:
Rivaroxaban is preferably provided in a micronized form with an average particle size less than 100µm, whereby at least 90% of the weight of the particles have a particle size below 100µm ([0033]), preferably less than 20µm, and more preferably less than 10µm ([0032]). This range encompasses the instantly claimed range (see MPEP 2144).
Regarding claim 15, Tyebji discloses:
Rivaroxaban is administered to treat various thromboembolic diseases ([0005]).
The recitation in claim 15 that the tablet is for use in the treatment of the claimed conditions is considered a statement of intended use that does not structurally distinguish the claimed tablet. Tyebji discloses a substantially similar tablet, which is inherently capable of administration to treat deep vein thrombosis or prevent venous thromboembolism after orthopedic surgery (e.g., NEJM at p. 2499 and 2500). Furthermore, Tyebji discloses rivaroxaban for thrombotic disease treatment generally.
The difference between the applied reference and the claimed invention is that the applied references may not teach the instantly claimed composition with particularity so as to amount to anticipation. See MPEP “[t]he identical invention must be shown in as complete detail as is contained in the ... claim.” Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).
However, the applied reference discloses the elements of the claimed composition with sufficient guidance, particularity, and with a reasonable expectation of success for the skilled artisan, that the invention would be prima facie obvious to one of ordinary skill in the art. Tyebji discloses embodiments of a tablet formulation comprising rivaroxaban, a pharmaceutically acceptable disintegrant, and one or more further pharmaceutically acceptable excipients which can be formulated into an orodispersible tablet. Tyebji teaches embodiments of the rivaroxaban composition with enough particularity that the skilled artisan would only be required to pick and choose between a small number of species taught by Tyebji to arrive at the instantly claimed invention. The skilled artisan would anticipate success in doing so because both Tyebji and the instantly claimed invention are directed to rivaroxaban tablet formulations.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Tyebji as applied to claims 1, 3-12, and 15 above, and further in view of Brniak (“The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs),” published 16 January 2016).
The disclosure of Tyebji is discussed above. Specifically –
Regarding claim 2, Tyebji discloses:
The composition of the invention can be in the form of an orodispersible tablet ([0061]). Although Tyebji does not expressly characterize orodispersible tablets as disintegrating in less than 3 minutes as required by claim 2, this property is well known in the pharmaceutical arts as a guideline for orodispersible tablet formulations as made obvious by Brniak.
Brniak teaches that according to Eur. Pharm. 7.0, orodispersible tablets should disintegrate in less than 3 minutes (p. 438). Furthermore, Brniak teaches the Food and Drug Administrations’ Guidance for Industry recommends the disintegration of orodispersible tablets should not exceed 30 seconds (p. 438).
Therefore, it would have been obvious, before the effective filing date of the claimed invention, to formulate the orodispersible tablet disclosed by Tyebji to disintegrate in less than 3 minutes as taught by Brniak. This modification would have been obvious to a skilled artisan because Brniak teaches disintegration of orodispersible tablets in less than 3 minutes is recommended by official medicinal quality standards and by governing regulatory organizations. The disintegration range taught by Brniak overlaps with the instantly claimed range in claim 2. See MPEP 2144.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over
Tyebji as applied to claims 1, 3-12, and 15 above, and further in view of
Pérez (US 2010/0297031 A1, published 25 November 2010).
The disclosures of Tyebji are discussed above. As it pertains to claims 13 and 14, Tyebji discloses:
A procedure for producing direct compression tablets comprising:
Mixing of pre-sieved rivaroxaban, sodium lauryl sulphate (surfactant), lactose monohydrate (filler), and hydroxypropyl methylcellulose (binder);
Mixing the mixture of step 1 with microcrystalline cellulose (diluent) and croscarmellose sodium (disintegrant);
Adding a magnesium stearate (lubricant) to the mixture; and
Compressing the blend into tablets ([0078]).
While Tyebji does not expressly disclose this process to produce orodispersible tablets, this is made obvious in view of Pérez.
Pérez discloses an orally disintegrating tablet obtainable by direct compression of a dry powdered mixture comprising calcium silicate, a diluent, a disintegrant, and an active ingredient (abstract, Example 1). Pérez further discloses direct compression is the easiest and most cost-effective method of manufacturing tablets ([0061]).
Tyebji discloses a rivaroxaban tablet comprising rivaroxaban particles, a pharmaceutically acceptable disintegrant, and further pharmaceutically acceptable excipients. Tyebji further discloses preparing the tablet by directly compressing a dry powdered mixture. Pérez teaches orodispersible tablets prepared by directly compressing a dry powdered mixture. It would have therefore been obvious to one of ordinary skill, before the effective filing date of the claimed invention, to prepare the directly compressed rivaroxaban tablet of Tyebji as the orodispersible tablet taught by Pérez. One of ordinary skill would be motivated to do so because direct compression with a disintegrant was a known technique for producing tablets that rapidly disintegrate in the mouth, thereby facilitating administration without water and improving ease of and adherence to administration. As person of ordinary skill would have a reasonable expectation of success because Tyebji already employs a disintegrant and a dry direct compression process compatible with the process taught by Pérez.
Citation of Relevant Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Benke (US PGPub. 2008/0026057 A1, published 31 January 2008) and Shah (WO2022/049602 A1, published 10 March 2022) both disclose rapidly releasing oral rivaroxaban tablets prepared by direct tabletting.
Conclusion
Claims 3, 5, and 9 are objected to. Claims 1-15 are rejected. No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Julia A. Rossi whose telephone number is (571)272-0138. The examiner can normally be reached M-Th 7:30-5:30 (MST).
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, Robert A. Wax can be reached at (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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/JULIA A. ROSSI/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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