DETAILED ACTION
Claims 87-138 are pending and under consideration on the merits.
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 .
Claim Rejections - 35 USC § 112
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 108, 112, and 118-123 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as 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 108 recites the formulation of claim 87 “comprising a disintegrant” in a recited range. This limitation is indefinite because claim 87 already recites a disintegrant. Is the disintegrant of claim 108 a different disintegrant than the one recited by claim 87, or the same? If the latter, claim 108 should recite “the disintegrant” instead of “a disintegrant.” Clarification is required. For the purpose of examination in view of the prior art, claim 108 has been given its broadest reasonable interpretation, which is that “a disintegrant” refers to the same disintegrant recited by claim 87. MPEP 2173.01.
Similarly, claim 112 recites “a lubricant,” but base claim 87 already recites a lubricant, and claims 118-124 recite “a diluent,” “a disintegrant,” and “a lubricant,” all of which are already recited by base claim 87. Therefore, these claims have the same problem as discussed with respect to claim 108 above. Clarification is required. For the purpose of examination in view of the prior art, these claims have been given their broadest reasonable interpretation, which is that “a diluent,” “a disintegrant,” and “a lubricant,” refer to the same diluent, disintegrant, and lubricant that are recited by claim 87. MPEP 2173.01.
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 87-138 are rejected under 35 U.S.C. 103 as unpatentable over Henary et al. (US Pat. Pub. 2020/0360374; published 11.19.2020) in view of Koziara et al. (US Pat. Pub. 2018/0177734; published 6.28.2018).
As to claims 87-138, Henary discloses a formulation comprising “Compound A” aka ”AMG 510” (synonymous with “sotorasib” of the present claims) and a method of treating cancer by administration of a therapeutically effective amount of the formulation to a subject in need thereof (claim 138)(paragraph 30). Henary discloses administering the sotorasib in a daily dose of 180, 360, 720, or 960 mg (see claim 1 of Henary), and teaches that a suitable dose may be calculated according to body weight, body surface areas, or organ size, and that determining the appropriate dose is routinely done by those of ordinary skill in the art without requiring undue experimentation (paragraph 38). Henary further teaches that the formulation may comprise a diluent such as a cellulose (paragraph 38), excipients such as starch or lactose (paragraph 52), a disintegrant, and a lubricant (paragraph 40), and also an excipient coating (paragraph 40).
Regarding claims 90-97, 118-124, and 126, the formulation may comprise from about 1 to about 90 wt% sotorasib, which encompasses the ranges and amounts recited by these claims (paragraph 42).
As to claims 87-138, Henary does not further expressly disclose that the diluent, disintegrant, and lubricant are present in amounts within the ranges or amounts of claims 87, 108, 112, or 118-128, that the lactose diluent is lactose monohydrate or that the cellulose diluent is microcrystalline cellulose as recited by claims 98-106 or 124-128, that the disintegrant is croscarmellose sodium or sodium starch glycolate (claims 109-111, 112-128), that the lubricant is magnesium stearate (claims 113-114, 124-128), or that the sotorasib is present in the amounts recited by claims 115-117 and 125-128. Nor does Henary expressly teach the presence of a plastic diluent such as microcrystalline cellulose and a brittle diluent such as lactose monohydrate in combination as recited by claims 87-88, wherein a first ratio by weight of the plastic diluent to brittle diluent is within the range of claims 87-88 and a second ratio of the plastic diluent to sotorasib and the brittle diluent together is within the ranges of claims 87-88, nor of the plastic diluent to sotorasib weight ratio of claim 89, and wherein the brittle and plastic diluents have average Heckel yield pressures within the ranges of claim 107. Nor does Henary expressly teach the sotorasib dissolves within the parameters of claims 135-137, or that the tablet is coated with a coating composition comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and/or a coloring agent as recited by claims 129-134.
Koziara discloses pharmaceutical tablet compositions comprising active ingredients along with excipients (paragraphs 4-5) such as 250mg or less of diluents/fillers such as microcrystalline cellulose, lactose monohydrate, or starches (claims 87 and 98-106), 0.5-5 wt% of lubricants of claims 87, and 113-114 such as magnesium stearate, calcium stearate, stearic acid, hydrogenated vegetable oil, glyceryl behenate, or talc (which encompasses the lubricant ranges of claims 87, 112, 118-124 and 126) and disintegrants such as croscarmellose or sodium starch glycolate of claims 87 and 108-111 (paragraphs 58, 60, 61, 62). Paragraph 74 discloses a specific embodiment of a tablet comprising lactose monohydrate (“brittle diluent” of the present claims”) and microcrystalline cellulose (“plastic diluent” of the present claims) as diluents in a total amount of 28.8 wt%, 1.3 wt% magnesium stearate as lubricant, and 6.2 wt% croscarmellose sodium as disintegrant, which results in a ratio of the plastic diluent to brittle diluent of about 4:1, which is within the ranges of claims 87-88. Regarding claims 129-134, the tablet is coated with a coating composition comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and indigo carmine (a “coloring agent”)(paragraph 74). Koziara teaches that in certain embodiments the tablet releases at least 80% or at least 90% of the active contained therein within 20 minutes measured using USP apparatus II with 75 rpm paddle speed at 37 degrees Celsius, which is within the ranges of claims 135-136 (paragraph 54).
As to claims 87-138, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the sotorasib formulation of Henary by selecting microcrystalline cellulose as the diluent and optionally in combination with lactose monohydrate, along with croscarmellose sodium or sodium starch glycolate as the disintegrant, and magnesium stearate as the lubricant, because Henary expressly teaches that its formulation may comprise lactose and celluloses as excipients without specifying any particular lactoses and celluloses, and further may comprise lubricants and disintegrants without specifying any particular lubricants, disintegrants, and Koziara expressly teaches that lactose monohydrate and microcrystalline cellulose are suitable forms of lactose and cellulose for use as diluents in pharmaceutical formulations, and that magnesium stearate is a suitable lubricant and croscarmellose sodium is a suitable disintegrant for use in pharmaceutical formulations, and further discloses a specific formulation comprising lactose monohydrate, microcrystalline cellulose, magnesium stearate, and croscarmellose sodium in combination, such that the skilled artisan reasonably would have expected that this combination of diluent, lubricant, and disintegrant would be suitable for use in the Henary pharmaceutical formulation. Such a modification is merely the combination of known elements according to known methods to achieve predictable results, which is prima facie obvious. MPEP 2143.
It further would have been prima facie obvious to select amounts of the lactose monohydrate, microcrystalline cellulose, magnesium stearate, and croscarmellose sodium that are within the presently claimed ranges and which results in a weight ratio of plastic diluent to brittle diluent within the range of claim 87, because Koziara discloses a specific embodiment comprising the use of amounts of lactose monohydrate, microcrystalline cellulose that reads on said ratio and which further comprises amounts of magnesium stearate and croscarmellose sodium that are close to the presently claimed amounts such that it can reasonably be assumed will result in similar properties (see MPEP 2155.05 I), and further because Koziara discloses the functions of these ingredients as being diluent, lubricants, and disintegrants, respectively, such that the skilled artisan would recognize that the amounts of these ingredients will affect the degree to which they are able to impart diluent, lubricating, and disintegrating abilities to the formulation, such that said amounts are result effective variables for which the skilled artisan would have been motivated to engage in an optimization process to determine the most effective amounts. MPEP 2144.05 I and IIA. The Office further notes that although the amounts of microcrystalline cellulose and lactose monohydrate diluents exemplified by Koziara are significantly less than the presently claimed amounts, the Koziara embodiment discussed above comprises four actives (i.e., elvitegravis, emtricitabine, tenofovir alafenamide hemifumarate, and cobicstate) which will take up a larger portion of the tablet composition, thereby requiring the use of less diluent. The skilled artisan would have been motivated to select higher amounts of the diluents for the Henary composition as it comprises only a single active. Additionally, discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding the second ratio of plastic diluent to sotorasib and brittle diluent together as recited by claims 87-88 and the ratio of plastic diluent to sotorasib of claim 89, since Koziara exemplifies amounts of the plastic and brittle diluents that read on the first ratio of claim 87 as discussed above and Henary teaches amounts of the sotorasib that are similar to the amounts recited by the dependent claims, the combination of Henary and Koziara is viewed as rendering the second weight ratio of claims 87-88 as well as the ratio of claim 89 prima facie obvious. It would have been well within the purview of the skilled artisan in the art of pharmaceutical formulations to test varying ratios of a diluent that is more plastic (and therefore more deformable) and a diluent that is more brittle (and therefore less deformable), relative to each other and to the other ingredients, in order to optimize the properties of the tablet, for example to ensure the appropriate friability, tensile strength, and hardness of the tablet (properties which are discussed by Koziara, for example, at Figure 9 and paragraphs 55-56), and ensure that the tablet disintegrates at an appropriate time to release the active within the time periods taught by Koziara. Additionally, discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
As to claims 90-97, and 115-128, it further would have been prima facie obvious to select amounts of the sotorasib active that are recited by claims 115-117, i.e., 120, 240, or 320 mg, and which are within the ranges of claims 90-97 and 118-128, because Henary expressly teaches the use of amount of sotorasib of 180, 360, 720, or 960 mg which includes amounts that are similar to the claimed amounts, and because Henary expressly suggests altering the amount of sotorasib to match a desired dosage form for a given patient and teaches that doing so involves only routine work without undue experimentation to one of ordinary skill in the art, and further because sotorasib is the active ingredient such that the amount of the sotorasib is a result effective variable which will affect the therapeutic efficacy of the composition for which the skilled artisan would have been motivated to engage in an optimization process to determine the most effective amounts. MPEP 2144.05 I and IIA. Additionally, discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claims 129-134, it further would have been prima facie obvious to coat the Henary tablet formulation with a coating composition comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and a coloring agent such as indigo carmine, because Henary expressly teaches the tablet may be coated without providing further details which would have motivated the skilled artisan to search the pharmaceutical tablet arts for disclosure of proper coating materials, which would have led to Koziara which teaches said ingredients as suitable for use as a coating over a pharmaceutical tablet comprising lactose monohydrate, microcrystalline cellulose, magnesium stearate, and croscarmellose sodium excipients, such that the skilled artisan reasonably would have expected that they could be used to form a coating over the Henary composition. Such a modification is merely the combination of known elements according to known methods to achieve predictable results, which is prima facie obvious. MPEP 2143.
The resulting formulation will possess the sotorasib release properties recited by claims 135-137 and an average Heckel yield pressure within the range of claim 107 because it comprises the same ingredients in the same amounts and a product cannot be separated from its properties. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima face case of either anticipated or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the countless ways that an Applicant may present previously unmeasured characteristics. When the prior art appears to contain the same ingredients that are disclosed by Applicants' own specification as suitable for use in the invention, a prima facie case of obviousness has been established, and the burden is properly shifted to Applicants to demonstrate otherwise. See MPEP 2112.01. Additionally, Koziara discloses specific embodiments for its formulation wherein the actives are released in similar amounts within similar times periods to those recited by the claims, such that the skilled artisan would recognize that incorporating the excipients from the Koziara embodiment into the Henary formulation would result in release profiles within the scope of the claims. Additionally, discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/
Primary Examiner, Art Unit 1600