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 .
DETAILED ACTION
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed August 12, 2025. The amendment, filed August 12, 2025, has been entered, wherein claims 1 – 4, 6, and 10 are amended.
Claims 1 – 10 are pending in this application and are currently examined.
Priority
3. The application is national stage application of PCT/IB2021/054728, filed May 29, 2021, which claims benefit of foreign priority document IN202041022831, filed June 1, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Objections
4. The objection of claims 1 – 4 and 6 in the previous Office Action, mailed June 6, 2025, is withdrawn in view of the amended claims.
The following are maintained / modified / new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed August 12, 2025, wherein claims 1 – 4, 6, and 10 are amended. Previously cited references have been used to establish the maintained / modified / new grounds of rejection.
Maintained / Modified Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 – 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Patel et al. (EP3052130B1, cited in the previous Office Action mailed June 6, 2025).
a. Independent claim 1 is directed to a fast water dispersible tablet comprising (a) about 50% w/w to about 85% w/w capecitabine, (b) about 10% w/w to about 25% w/w diluents, (c) about 1% w/w to about 5% w/w disintegrants, (d) about 1% w/w to about 2% w/w glidant, and (e) about 0.1% w/w to about 2% w/w lubricants. Dependent claim 2 is directed to the fast water dispersible tablet, wherein the diluent is microcrystalline cellulose. Dependent claim 3 is directed to the fast water dispersible tablet, wherein the disintegrant is croscarmellose sodium. Dependent claim 4 is directed to the fast water dispersible tablet, wherein the glidant is talc and colloidal silicon dioxide. Dependent claim 5 is directed to the fast water dispersible tablet, wherein the lubricant is magnesium stearate.
Patel et al. teach a pharmaceutical composition comprising fixed dose combination of capecitabine and cyclophosphamide for treating cancer diseases (para. [0001]). In one example, the pharmaceutical composition comprises 400 mg capecitabine , 95.82 mg microcrystalline cellulose, 36.5 mg croscarmellose sodium, 14.0 mg magnesium stearate, and 10.79 mg of talc and colloidal silicon dioxide. The weight of the total coated tablet is 715.0 mg (page 7 – 8, Example 3).
Accordingly, the weight percentage of capecitabine, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, and the glidants (talc and colloidal silicon dioxide) are 55.9%, 13.4%, 5.1%, 2.0%, and 1.5%, respectively.
For these reasons above, Patel et al. anticipate the claimed invention.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed August 12, 2025, have been fully considered and are found to be not persuasive.
Regarding Patel et al., Applicant argues that Patel et al. do not teach the fast water dispersible tablets of capecitabine. In response to applicant's argument that Patel et al. does not teach a “fast water dispersible tablet”, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Maintained / Modified 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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
Claims 6 – 10 are rejected under 35 U.S.C. 103 as being unpatentable over Patel et al. (EP3052130B1, cited in the previous Office Action mailed June 6, 2025) in view of Gogia et al. (WO2004/014337A2, cited in the previous Office Action mailed June 6, 2025).
b. Regarding claims 6 – 10, Patel et al. teach a pharmaceutical composition comprising fixed dose combination of capecitabine and cyclophosphamide for treating cancer diseases (para. [0001]). In one example, the pharmaceutical composition comprises 400 mg capecitabine , 95.82 mg microcrystalline cellulose, 36.5 mg croscarmellose sodium, 14.0 mg magnesium stearate, and 2.65 mg of colloidal silicon dioxide. The weight of the total coated tablet is 715.0 mg (page 7 – 8, Example 3). Examples of disintegrant for first layer include, without being limited to, croscarmellose sodium, crospovidone, sodium starch glycolate, starch, pregelatinized starch, and combination thereof (para. [0035]).
However, Patel et al. do not teach that about 1% w/w to about 2% w/w of colloidal silicon dioxide is present in both intragranular and extragranular portion of the tablet
Gogia et al. teach the invention relates to dispersible tablets of cephalexin (Abstract). In one embodiment, colloidal silicon dioxide is present in both intragranular and extragranular layers, wherein colloidal silicon dioxide is 1.5% in the intragranular portion and 0.5% in the extragranular portion. This particular example also comprises 12.00 mg crospovidone and 12.00 mg colloidal silicon dioxide in the intragranular layer and 4.00 mg colloidal silicon dioxide and 10.00 mg magnesium stearate in the extragranular layer (Page 8, Example 1). The dispersible tablets maintain the same advantages as conventional tablets and capsules in terms of their accuracy of dosing and ease of handling. They also possess the advantages of suspensions in terms of better bioavailability and increased compliance with children, elderly and patients who have difficulty in swallowing. These tablets have low friability and therefore are easily transportable and no refrigeration is required (page 7, lines 16 – 20).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute croscarmellose sodium with crospovidone as taught by Patel et al. because Patel et al. teach that crospovidone is another example of disintegrant listed. It would have been obvious to substitute as the substitution will yield predictable results. It would have been prima facie obvious to combine the tablet formulation of capecitabine as taught by Patel et al. with the dispersible tablet formulation in view of Gogia et al. because Gogia et al. explicitly teach that the dispersible tablet has the same advantages as conventional tablet and also possess other advantages. One would have been motivated to combine the two formulations because it is predicted to yield an improved formulation of capecitabine. For the amount of each component in the tablet, one would have performed a routine experimentation to discover the best amount of each component for the optimal treatment characteristics. Therefore, one of the skills in the art would have had a reasonable expectation of success to substitute croscarmellose sodium with crospovidone and to combine the tablet formulation of capecitabine as taught by Patel et al. with the dispersible tablet formulation in view of Gogia et al. because Patel et al. discloses all the components used in the capecitabine and Gogia et al. disclose the dispersible formulation that has more benefits. The combination of teachings will yield a predictable improved formulation of capecitabine.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed August 12, 2025, have been fully considered and are found to be not persuasive.
Regarding Patel et al., Applicant argues that Patel et al. do not teach the fast water dispersible tablets of capecitabine. In response to applicant's argument that Patel et al. does not teach a “fast water dispersible tablet”, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding Gogia et al., Applicant argues that Gogia et al. is not relevant because Gogia et al. teach cephalexin tablets and employs a binder solution, whereas the present invention relates to capecitabine and omits a binder. However, the examiner respectfully notes that Gogia et al. is not relied upon for its disclosure of the active ingredient but rather for its teaching of fast-disintegrating water-dispersible tablet formulations, which are applicable to a wide variety of active pharmaceutical agents. One of ordinary skill in the art would have been motivated to apply such known fast-disintegrating tablet technology to capecitabine, particularly since rapid disintegration is a universally desirable property. Moreover, Gogia et al. disclose the use of colloidal silicon dioxide as an excipient. Applicant’s claimed modification of positioning colloidal silicon dioxide intra- and extragranularly, while omitting a binder, represents routine optimization of excipient placement and selection, which is within the skill of the formulator. Disintegration time is a recognized obvious to a person of ordinary skill in the art to adjust excipient placement or omit binders to optimize tablet properties.
Finally, Applicant provides the synergistic activity when colloidal silicon dioxide is formulated into both intra- and extragranular layer, which a shorter disintegration time is being measured. The examiner acknowledged the results. However, the examiner is not able to determine whether the results are unexpected because Haeberlin et al. (US8617598B2) discloses that the addition of colloidal silicon dioxide to a disintegrant will promote disintegration. Colloidal silicon dioxide is known from the prior art primarily as a lubricant in pharmaceutical compositions. Where it is used for such purposes, silicon dioxide typically comprises around 0.5% by weight of the composition. The inclusion of 1 to 5% by weight of colloidal silicon dioxide has been found to be particularly effective in promoting disintegration of a macrolide solid dispersion in an aqueous solution, when combined with another disintegrant (Col. 2, lines 55 – 64). Apeji et al. (Journal of Pharmacy, 2017, Vol. 2, Issue 1, page 55 – 69, Reference included with PTO-892) teach that the role of colloidal silicon dioxide in co-processed mixture is to promote flowability of maize starch by reason of its action as a glidant. It is also known to enhance compressibility when deposited on the surface of co-processed particles providing rough surfaces that facilitates particulate bonding by mechanical interlocking. Rapid disintegration of tablets has been associated with colloidal silicon dioxide due to its ability to create a porous network that drives water uptake into the tablet resulting in a rapid burst of the tablet in an aqueous medium during disintegration (page 56, Right Col., para. 1). Apeji et al. further disclose that all the batches of tablets containing colloidal silicon dioxide disintegrate within 1 minute (page 66, Right Col., para. 1). Moreover, Mathivanan (Journal of Global Trends in Pharmaceutical Sciences, 2015, Vol. 6, Issue 2, page 2611 – 2620, Reference included with PTO-892) teaches that the combination of microcrystalline cellulose, crospovidone, and colloidal silicon dioxide at the intragranular level demonstrates the shortest disintegration time (page 2615, Table 1). Based on these support, the results provided by Applicant are not unexpected. Therefore, the addition of colloidal silicon dioxide in the intragranular level reduces the disintegration time is predictable.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the maintained / modified ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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