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 . Claims 1-8 filed November 21, 2022 are currently pending. Claim 1 is independent.
Priority
Acknowledgement is made of the national stage entry of PCT/IB2021054199 filed 05/17/2021 which claims foreign priority to Application 202041020998 filed 05/19/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/04/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112-Paragraph A
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 1, 3-8 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 description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See, e.g., In re Wilder, 22 USPQ 369, 372-3 (Fed. Cir. 1984). (Holding that a claim was not adequately described because the specification did ‘little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.') Mere indistinct terms (such as "5-fluoropyrimidine derivatives" and “isomers of 5-fluoropyrimidine derivatives” found within instant claim 1), however, may not suffice to meet the written description requirement. This is particularly true when a compound is claimed in purely functional terms. See Univ. of Rochester v. G.D. Searle, 69 USPQ2d 1886 (CAFC 2004) at 1892, stating: "[T]he appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. A description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) described even in terms of its functioning of lessening inflammation of tissues fails to distinguish any steroid from others having the same activity or function. A description of what a material does, rather than of what it is, usually does not suffice The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. (Emphasis added).
Conversely, a description of a chemical genus will usually comprise a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. See Univ. of Calf. V. Eli Lilly, 43 USPQ 2d 1398, 1406 (Fed. Cir. 1997). This is analogous to enablement of a genus under 35 U.S.C. 112, first paragraph, by showing the enablement of a representative number of species within the genus.
A chemical genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has substantial variance, the disclosure must describe a sufficient number of species to reflect the variation within that genus. See MPEP 2163.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. MPEP 2163.
Here, the specification does not provide a reasonably representative disclosure of useful "5-fluoropyrimidine derivatives” or “isomers of 5-fluoropyrimidine derivatives” Paragraph [006] of the specification describes the genus of “5-fluoropyrimidines derivatives” by its function and not its structure. “5-fluoropyrimidine derivatives is an example of a prodrug of 5-FU with a pharmacological mode of action like capecitabine. Endogenous enzymes convert 5-fluoropyrimidine derivatives to 5-fluorouracil (5-FU). Both normal and tumor cells metabolize 5-FU to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). As shown in Alvarez (Expert Opinion Thera Patents Vol. 22 pages 107-123 published 2012) the generic “5-fluoropyrimidine derivative” embraces a wide array of compounds comprising chemical structures with no structural overlap including capecitabine, ftorafur/tegafur, eniluracil/GW-776, doxifluridine, gemcitabine and polysaccharide 5-FU prodrugs.
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Said genus embraces diverse structures relative to the base 5-fluorouracil compound (abstract, pages 111-113Figure 1).
However, the specification discloses NO “derivatives” of 5-fluoropyrimidine other than compound CLX-115 or (2R, 3R, 4R, 5R)-2-(5-Fluoro-4-octanamido 2-oxopyrimidine-1(2H)-y1) -5-methyltetrahydrofuran-3,4-diyldiacetate as recited in claim 2 and [0060] of the instant specification. Nor does the specification provide blaze-marks to defining structural limitations and physical properties encompassing a "5-fluoropyrimidine derivative" or how far the structure of a scaffold may vary to be encompassed in the genus either a structural “derivative of 5-fluoropyrimidine” or a functional “derivative of 5-fluoropyrimidine”, and which compounds lie inside or alternatively, outside the purported genus.
Additionally, the specification does not provide a reasonably representative disclosure of useful "5-fluoropyrimidine derivatives" and “isomers of 5-fluoropyrimidine derivatives” generally, a potentially huge genus inclusive of many different compounds having widely divergent structures and functions (i.e., a “isomer” embraces a constitutional isomer which comprises the same molecular formula with different connectivity"). Specifically, the specification discloses NO "5-fluoropyrimidine derivatives” other than the distinct species 2R, 3R, 4R, 5R)-2-(5-Fluoro-4-octanamido 2-oxopyrimidine-1(2H)-y1) -5-methyltetrahydrofuran-3,4-diyldiacetate in claim 2. The specification also does not disclose “isomers of 5-fluoropyrimidine derivatives” nor provide blaze-marks to defining structural limitations encompassing an "isomer or mixture of isomers of 5-fluoropyrimidine derivative" and where isomerization could occur on the chemical framework.
The lack of examples is not viewed as being reasonably representative of the genus in its claimed scope because no readily apparent combination of identifying characteristics is provided, other than the disclosure of those specific species as examples of the claimed genus.
Claim Rejections - 35 USC § 112-Paragraph 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 1-8 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.
Claim 1 is directed to a pharmaceutically acceptable composition comprising: a) an active ingredient selected from 5-fluropyrimidine derivatives, their isomers, stereoisomers, diastereomers, enantiomers, prodrug and pharmaceutically acceptable salts thereof in an amount of 100- 3000 mg and comprising at least 60-85% by weight of the formulation; b) one or more disintegrants or super disintegrants in an amount of 0.5 to 6 % by weight; c) one or more surfactants in an amount of 0.1 to 5% by weight; d) one or more binders in an amount of 0.2 to 5%by weight; and e) at least one lubricant in an amount of 0.3 to 3% by weight; wherein the pharmaceutically acceptable composition exhibits a friability of not more than 1 to 10%.
Claim 1 recites the limitation "the formulation". There is insufficient antecedent basis for this limitation in the claim, as the preceding text of the claim does not recite “a formulation”. Rather, the preceding text of the claim recites the phrase “a pharmaceutically acceptable composition”. Accordingly, one of ordinary skill in the art prior to the time of the invention would not have been reasonably apprised of the metes and bounds of the subject matter for which Applicant was presently seeking protection. To overcome this rejection, Applicant is invited to amend the phrase “the formulation” to “the pharmaceutically acceptable composition”
Claims 1, 3-8 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “isomers and stereo isomers” of 5-fluoropyrimidine derivates, prodrugs of 5-fluoropyrimidines and pharmaceutically acceptable salts of 5-fluoropyrimidines. The phrase “isomers” embraces constitutional isomers which comprises the same molecular formula with different connectivity. Claim 1 also recites “enantiomers and diastereomers” of 5-fluoropyrimidine derivates which is the narrower statement of the range/limitation “isomers and stereo isomers of 5-fluoropyrimidine derivates”. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 4 and 7 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.
Claim 4 contains the trademark name “carbomer” while claim 7 contains the trademark/trade name “Tween 80”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe polyoxyethylene sorbitan monooleate or polysorbate 80. CARBOMER is a US trademark for specialty chemicals. (Serial number 78242328.). Accordingly, the identification/description is indefinite.
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.
Claim(s) 1, 3-8 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Sehgal (WO2016/203358 published 12/22/2016) and Patel (US2017/0304328 published 10/26/2017).
Claim interpretation is as follows: Claim 1 is directed to a pharmaceutically acceptable composition comprising: a) an active ingredient selected from 5-fluropyrimidine derivatives, their isomers, stereoisomers, diastereomers, enantiomers, prodrug and pharmaceutically acceptable salts thereof in an amount of 100- 3000 mg and comprising at least 60-85% by weight of the formulation; b) one or more disintegrants or super disintegrants in an amount of 0.5 to 6 % by weight; c) one or more surfactants in an amount of 0.1 to 5% by weight; d) one or more binders in an amount of 0.2 to 5%by weight; and e) at least one lubricant in an amount of 0.3 to 3% by weight; wherein the pharmaceutically acceptable composition exhibits a friability of not more than 1 to 10%.
Given the broadest reasonable interpretation of the phrase “5-fluoropyrimidine derivatives” found within [006] of the specification, wherein the genus of “5-fluoropyrimidine derivatives” is described by its function and not its structure, “(5-fluoropyrimidine derivatives is an example of a prodrug of 5-FU with a pharmacological mode of action like capecitabine. Endogenous enzymes convert 5-fluoropyrimidine derivatives to 5-fluorouracil (5-FU)), the examiner has interpreted that any compound that is a prodrug of 5-FU and has a pharmacological mode of capecitabine reads on the presently claimed genus of “5-fluoropyrimidine derivative”. As recited in Backynsky (US2008/0085310 published 04/10/2008), capecitabine is a prodrug of 5-FU and has the pharmacological mode of capecitabine ([0002][-0003]). Thus, the claims embrace pharmaceutically acceptable composition comprising capecitabine.
Sehgal (WO2016/203358 published 12/22/2016) teaches orally administered pharmaceutically acceptable dosage forms for the 5-fluoropyrimidine derivative capecitabine (abstract).
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Embodied within Sehgal includes a tablet composition comprising 50-80% wt. capecitabine, 0.5-1.5% of the lubricant magnesium stearate, 3-5% wt. of the disintegrant microcrystalline cellulose, 2-4% wt. of the binder hydroxypropyl methylcellulose cps (page 15). Sehgal teaches wherein the tablet comprises a film coat prepared from hydroxypropyl methylcellulose, talc, titanium, the polyethylene glycol and purified water, and is present in 2-4% wt. of the tablet composition (pages 15-16). The 5-fluoropyrimidine derivative capecitabine is present in 150 mg -750 mg of the composition (page 12). The amount and percent weight of the 5-fluoropyrimidine derivative capecitabine, disintegrant, binder and lubricant in the tablet composition of Sehgal overlap with the amounts of 5-fluoropyrimidine derivative, disintegrant, binder and lubricant found in the presently claimed composition. Applicant is reminded of MPEP 2144.05 wherein the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Regarding claim 7, said capecitabine tablet is formulated for prolonged release (pages 14-15). Regarding claim 8, said capecitabine tablet composition is administered to treat cancer in a subject in need.
The difference between the presently claimed composition and that of Sehgal is that Sehgal does not specifically teach wherein the capecitabine tablet formulation comprises one or more surfactants in a concentration of 0.1 to 5% wt. of the composition.
Patel (US2017/0304328 published 10/26/2017) teaches pharmaceutical tablets comprising the 5-fluoropyrimidine derivative capecitabine. Patel teaches film coating said capecitabine tablet using a coating solution of polyethylene glycol, the non-ionic surfactant polysorbate 80, carboxymethylcellulose, talc and titanium dioxide and eudragit NE30D ([0121]-[0142]), wherein the non-ionic surfactant is present in 0.08% wt. of the tablet composition (0.98 mg of 1215.00 mg total) ([0121]-[0142]).
Therefore, one of ordinary skill in the art of preparing tablets of the 5-fluoropyrimidine derivative capecitabine comprising 50-80% wt. capecitabine, 0.5-1.5% of the lubricant magnesium stearate, 3-5% wt. of the disintegrant microcrystalline cellulose, 2-4% wt. of the binder hydroxypropyl methylcellulose cps and a film coating as taught by Sehgal, said skilled artisan would have found it prima facie obvious to substitute the film coating prepared from hydroxypropyl methylcellulose, talc, titanium, the polyethylene glycol and purified water in 2-4% wt. of the tablet composition of Sehgal for a film coating comprising a solution of polyethylene glycol, the non-ionic surfactant polysorbate 80, carboxymethylcellulose, talc and titanium dioxide and eudragit NE30D in view of Patel, arriving at the presently claimed composition.
MPEP 2143 provides rationale for a conclusion of obviousness including (B): Simple substitution of one known element for another to obtain predictable results;
In the present case, a composition comprising hydroxypropyl methylcellulose, talc, titanium, the polyethylene glycol and purified water and a composition comprising a solution of polyethylene glycol, the non-ionic surfactant polysorbate 80, carboxymethylcellulose, talc and titanium dioxide and eudragit NE30D were each taught in the prior art as suitable film coatings for tablets for the 5-fluoropyrimidine derivative capecitabine. Accordingly, said skilled artisan would have readily predicted that the formulating a tablet of the 5-fluoropyrimidine derivative capecitabine comprising 50-80% wt. capecitabine, 0.5-1.5% of the lubricant magnesium stearate, 3-5% wt. of the disintegrant microcrystalline cellulose, 2-4% wt. of the binder hydroxypropyl methylcellulose cps and a film coating as taught by Sehgal, wherein said film coating comprised polyethylene glycol, the non-ionic surfactant polysorbate 80, carboxymethylcellulose, talc and titanium dioxide and eudragit NE30D of Patel, said tablet would have delivered the effective antineoplastic agent to the targeted tissue in the afflicted subject.
Regarding the limitation wherein the non-ionic surfactant is present in 0.1-5% wt. of the composition, it is considered well within the capabilities of one of ordinary skill in the art to optimize the amount of non-ionic surfactant in the 5-fluoropyrimidine derivative composition to provide optimal solubility conditions for the pharmaceutically active agent. The amount of each non-ionic surfactant in the 5-fluoropyrimidine derivative pharmaceutical composition is a result effective parameter that will affect the physical properties of the final composition. The amount of non-ionic surfactant, such as polysorbate 80 in a composition, is clearly a results effective parameter that a person of ordinary skill would routinely optimize. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the ratios polysorbate 80 in the capecitabine tablet of Patel provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal amount of non-ionic surfactant to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the composition and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Lastly, regarding the functional limitation wherein the composition exhibits a friability of not more than 1-10%, Applicant is reminded that properties (such as a friability of not more than 1-10%) that accrue from a process step of formulating a composition containing a 5-fluoropyrimidine derivative in 60-80% wt. of the composition, a disintegrant in 0.5-6% wt. of the composition, a binder in 0.2-5% wt. of the composition, a surfactant in 0.1-5% wt. of the composition and a lubricant in 0.3-3% wt. of the composition, said properties are considered characteristic features of the claimed product.
It is noted that MPEP 2112 discusses the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
In the present case the burden is shifted to Applicant to prove that the resulting capecitabine tablet embodied from the combined teachings of Sehgal and Patel does not have a friability of no more than 1-10%.
Claim(s) 2 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Sehgal (WO2016/203358 published 12/22/2016) and Patel (US2017/0304328 published 10/26/2017) as applied to claims 1, 3-8 in view of Kandula (WO2018/002739 published 01/04/2018).
As disclosed above, the combination of Sehgal and Patel render obvious a pharmaceutical tablet composition comprising the chemotherapeutic agent 5-fluoropyrimidine derivative capecitabine wherein capecitabine is present in 150-750 mg of the tablet composition, comprises 50-80% wt. of the tablet composition, and further comprises 0.5-1.5% of the lubricant magnesium stearate, 3-5% wt. of the disintegrant microcrystalline cellulose, 2-4% wt. of the binder hydroxypropyl methylcellulose cps and a film coating comprising a solution of polyethylene glycol, the non-ionic surfactant polysorbate 80, carboxymethylcellulose, talc and titanium dioxide and eudragit NE30D. The combination of Sehgal and Patel teach that said film coating is a suitable film coating to apply to capecitabine tablets in order to deliver the art-recognized antineoplastic agent to the targeted tissue in the afflicted subject.
The difference between the present claims and that of the combination of Sehgal and Patel is that the combination of Sehgal and Patel does not specifically teach wherein the 5-fluoropyrimidine derivative is (2R, 3R, 4R, 5R)-2-(5-Fluoro-4-octanamido 2-oxopyrimidine-1(2H)-y1) -5-methyltetrahydrofuran-3,4-diyldiacetate.
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Kandula (WO2018/002739 published 01/04/2018) teaches compounds of Formula (I) (abstract). Embraced within Formula (I) is compound Formula (I-5) shown above, which corresponds to CLX-115 or (2R, 3R, 4R, 5R)-2-(5-Fluoro-4-octanamido 2-oxopyrimidine-1(2H)-y1) -5-methyltetrahydrofuran-3,4-diyldiacetate as recited in [0060] of the instant specification. Kandula teaches tablet pharmaceutical compositions and that said pharmaceutical composition comprises 500-800 mg of the compound of Formula (I), Kandula teaches tablet compositions for compounds of Formula (I) wherein said compound is present in 30-70% wt. of the composition, and is formulated with disintegrants, binders, surfactants and lubricants, including the disintegrant microcrystalline cellulose, the binder hydroxypropyl methylcellulose and the lubricant magnesium stearate . Kandula teaches wherein the disintegrant is present in 2-20% wt. of the composition, the binder is present in 1-30% wt. of the composition and the lubricant is present in 1-5% wt. of the composition ([0082]-[0084], [0109], [0136]-[0143]). The amount of active agent, disintegrant, binder and lubricant embodied within Kandula overlaps with the amount embodied in the present claims ([0057], [0062]). Applicant is reminded of MPEP 2144.05 wherein the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Kandula teaches that the compounds of Formula (I) are typically compounds of capecitabine in which the free hydroxyl groups of capecitabine are conjugated with a fatty acid in an ester conjugate form ([0009]).
Therefore, one of ordinary skill in the art prior to the time of the invention knowing a tablet composition containing 0.5-1.5% of the lubricant magnesium stearate, 3-5% wt. of the disintegrant microcrystalline cellulose, 2-4% wt. of the binder hydroxypropyl methylcellulose cps and a film coating comprising polyethylene glycol, the non-ionic surfactant polysorbate 80, carboxymethylcellulose, talc and titanium dioxide and eudragit NE30D is a suitable tablet formulation for the 5-fluoropyrimidine derivative compounds (capecitabine) as taught by the combination of Sehgal and Patel, said skilled artisan would have found it prima facie obvious to apply the tablet formulation of the 5-fluoropyrimidine derivative capecitabine to a capecitabine derivative, such as (2R, 3R, 4R, 5R)-2-(5-Fluoro-4-octanamido 2-oxopyrimidine-1(2H)-y1) -5-methyltetrahydrofuran-3,4-diyldiacetate in view of Kandula, arriving at the presently claimed composition.
MPEP 2143 provides rationale for a conclusion of obviousness including (C): Use of a known technique to improve similar products in the same way;
As disclosed above, the combination of Sehgal and Patel use the known technique of formulating a pharmaceutically acceptable tablet of the 5-fluoropyrimidine derivative capecitabine with 0.5-1.5% of the lubricant magnesium stearate, 3-5% wt. of the disintegrant microcrystalline cellulose, 2-4% wt. of the binder hydroxypropyl methylcellulose cps and a film coating comprising polyethylene glycol, the non-ionic surfactant polysorbate 80, carboxymethylcellulose, talc and titanium dioxide and eudragit NE30D as said tablet formulation is suitable to deliver the art-recognized antineoplastic agent to the targeted tissue. Coupled with the knowledge that it is suitable to formulate (2R, 3R, 4R, 5R)-2-(5-Fluoro-4-octanamido 2-oxopyrimidine-1(2H)-y1) -5-methyltetrahydrofuran-3,4-diyldiacetate with microcrystalline cellulose, hydroxypropyl methylcellulose and magnesium stearate in overlapping concentrations as found in the combined teachings of Sehgal and Patel, it would have been obvious to have selected various capecitabine tableting techniques from within the prior art of Sehgal and Patel above and apply it to the art-recognized capecitabine mimic of Kandula, arriving at the claimed methodology “yielding no more than one would expect from such an arrangement”.
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621