DETAILED ACTION
Notice of 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 .
Status of the Claims
The amendments filed 5/22/2026 have been entered.
Response to Arguments
Applicant’s arguments, filed 5/22/2026, have been fully considered.
The nonstatutory obvious type double patenting rejections of claims based on 17/998,198 and 17/998,202 are WITHDRAWN.
Applicant traverses the rejection of claims under 35 U.S.C. 103(a) as being unpatentable over Snyder et al (US 2018/0296574; of record) in view of Hedley et al (US 2018/0311224; of record) and Benjamin et al (US 2016/0015816; of record).
Applicant first argues that “Snyder, Hendley and Benjamin do not teach or suggest the claimed active pharmaceutical ingredients in a granule composition comprising the claimed combination of excipients” (Applicant Arguments, Page 7). As argued by Applicant, “Snyder does not teach a pharmaceutical composition comprising the claimed excipients” and “Benjamin, which allegedly supplies the claimed composition excipients, relates to a composition for a single API whereas the claimed composition includes a fixed combination of two APIs” (Applicant Arguments, Page 8).
The argument is not found persuasive. Although Benjamin et al do not specifically disclose granules comprising multiple APIs, there is nothing to suggest that a second API could not be included in the granules of Benjamin et al. Indeed, Benjamin et al teach that “[i]n some embodiments of the invention, the solid composition further comprises at least one additional pharmaceutical ingredient” which includes any ingredient “so long as the material is not generally deleterious to a human subject when the solid composition is administered at dosing quantities” (Paragraph 0054).
Applicant next argues that the granules of Benjamin et al relate “to an entirely different class of compound” – namely a “glucokinase (GK) activator” as opposed to a “poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor” and an “inhibitor of human cytochrome P45017α” as claimed, having “different mechanisms of action... [and] different chemical structures” (Applicant Arguments, Page 8). As further argued by Applicant, “[n]othing... indicates that those of ordinary skill in the formulation arts would have viewed UD1 and a combination of abiraterone acetate and niraparib tosylate monohydrate as comparable, much less interchangeable” and “the Office fails to identify any reason to believe that a skilled formulator would have substituted one UD1 for the claimed combination of APIs in a granule composition without carefully considering chemical differences that might influence whether a suitable granule composition may be obtained or the ultimate stability and properties of the composition” (Applicant Arguments, Page 8).
The argument is not found persuasive. While it is recognized that the API utilized in the granules of Benjamin et al are structurally and functionally different from the APIs of the instantly claimed granules and, moreover, that “[t]he preparation of... solid compositions presents a number of technical problems that may vary depending on the chemical and physical properties of the active compound” (Paragraph 0021), a person of ordinary skill in the art would have nevertheless understand the granulation platform of Benjamin et al as generic pharmaceutical technology applicable to other APIs. There is nothing about the granules of Benjamin et al that are specific to GK activators. Rather, in the instant case, (1) the prior art elements perform the function specified in the claim (that is, the pharmaceutically acceptable carriers utilized in formulating the GK activator-comprising granules of Benjamin et al would function in the same way in formulating the instantly claimed abiraterone acetate- and niraparib tosylate monohydrate-comprising granules, with only insubstantial differences); (2) the claimed elements (i.e., the instantly claimed the pharmaceutically acceptable carriers) and their function was known in the art; (3) a person of ordinary skill in the art would have recognized the interchangeability of the elements and could have substituted one known element for another; and (4) the results of the substitution would have been predictable. As stated by the Court in KSR International Co., v. Teleflex Inc., 127 US 1727 (2007), “when a patent ‘simply arranges old elements with each performing the same function it had been known to perform’ and yields no more than one would expect from such an arrangement, the combination is obvious” (quoting Sakraida v. AG Pro, Inc., 425 US 273 (1976)). Furthermore, as noted by the court in In re Fout, 675 F.2d 297 (CCPA 1982), an express suggestion to substitute one equivalent component for another is not necessary to render such substitution obvious.
Applicant next argues that, in contrast to the prior art, “Applicant unexpectedly achieved a granule combination in which two APIs have comparable dissolution profiles” (Applicant Arguments, Page 9). In particular, Applicant points to Figures 5A and 5B which “reveal that when formulated in the claimed fixed-dose granule composition, abiraterone acetate and niraparib tosylate monohydrate have comparable dissolution profiles relative to each other and to abiraterone acetate alone. Surprisingly, the claimed fixed-dose granule composition shows an improved dissolution profile relative to dissolution profile of niraparib tosylate alone” (Applicant Arguments, Pages 9-10).
It is well settled that a showing of unexpected results is generally sufficient to overcome a prima facie case of obviousness. In re Albrecht, 514 F.2d 1389 (CCPA 1975). In Figures 5A and 5B, Applicant demonstrates that administration of “a combination of single agents being one capsule of 100-mg eq. niraparib, in tosylate monohydrate form, and 2 tablets of 250-mg abiraterone acetate” results in complete dissolution of abiraterone (Figure 5A (SA 100 mg + SA 2x250 mg)), only about 25-30% of niraparib is dissolved (Figure 5A (SA 100 mg + SA 2x250 mg)). However, when either “50-mg eq. niraparib, in tosylate monohydrate form” or “100-mg eq. niraparib, in tosylate monohydrate form” is formulated as a single fixed dose combination with “500-mg abiraterone acetate”, 100% of niraparib is dissolved.
Yet, whereas the Specification discloses the makeup of the fixed dose combinations (see, e.g., Pages 45-46, Tables 1-4), it is unclear what ingredients were included in the “combination of single agents being one capsule of 100-mg eq. niraparib, in tosylate monohydrate form, and 2 tablets of 250-mg abiraterone acetate”. At minimum, it does not appear that the single agents were formulated using the same excipients as the fixed dose combination, rendering it impossible to determine whether the differing dissolution of niraparib in the fixed dose combination is, in fact, unexpected. Evidence demonstrating:
(a) that the single agents, when formulated as single agents using the same excipients as used in the fixed dose combination, provide different dissolution profiles when compared to the fixed dose combination would be considered unexpected; and/or
(b) that the combination of niraparib, in tosylate monohydrate form, and abiraterone acetate in a single fixed dose combination comprising whatever excipients are present in the single agent formulations tested in Figures 5A and 5B do not result in 100% of niraparib being dissolved would also be considered unexpected.
The evidence of record is not sufficient to demonstrate unexpected results.
Moreover, even if Applicant’s argument that Figures 5A and 5B demonstrate unexpected results was considered to be persuasive, Applicant is reminded that “the objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support”. In re Clemens, 622 F.2d 1029 (CCPA 1980). In the instant case, the fixed dose formulations evaluated in Figures 5A and 5B and providing the alleged unexpected results comprise, in addition to abiraterone acetate, niraparib tosylate monohydrate, SLS and crospovidone as recited by claim 1, HPMC, purified water, lactose monohydrate, silicified MCC, colloidal anhydrous silica, and magnesium stearate organized into a unique granule structure. As such, even if Applicant’s argument that Figures 5A and 5B demonstrate unexpected results was considered to be persuasive, the claims are not drafted commensurate in scope with the formulations evaluated in Figures 5A and 5B.
Lastly, Applicant traverses the nonstatutory double patenting of claims based on copending Application No. 18/833,519. As argued by Applicant, “the 519 Application has a later patent term filing date than the instant application” and “[a]ccording to the MPEP, if an application under examination has the earlier patent term filing date, ‘the examiner should withdraw the [provisional nonstatutory double patenting] rejection in the application having the earlier patent term filing date and permit the application to issue as a patent” citing MPEP 804(I)(B)(1)(b)(i).
Applicant is directed to the full text of MPEP 804(I)(B)(1)(b)(i) which states:
If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent.
For all the foregoing reasons, the claims are MAINTAINED rejected.
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.
Claim 99 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 99 is drawn to the granule composition of claim 65, “wherein the dissolution profile of the abiraterone acetate and the dissolution profile of the niraparib tosylate monohydrate are measured by... UHPLC”.
Claim 65 does not provide support for measurement of a dissolution profile as recited by claim 99.
As such, claim 99 lacks antecedent basis in claim 65 and is thus rejected as indefinite.
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.
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 65-70 and 97-98 are rejected under 35 U.S.C. 103(a) as being unpatentable over Snyder et al (US 2018/0296574; of record) in view of Hedley et al (US 2018/0311224; of record) and Benjamin et al (US 2016/0015816; of record).
As amended, claim 65 is drawn to a granule composition comprising:
granules consisting essentially of:
abiraterone acetate,
niraparib tosylate monohydrate, and
a pharmaceutically acceptable carrier;
wherein the pharmaceutically acceptable carrier comprises:
a wetting agent that is sodium lauryl sulfate;
a disintegrant that is crospovidone; and
further comprising a glidant, lubricant and binder (claim 66), more specifically, wherein:
the glidant is colloidal anhydrous silica (claim 69);
the lubricant is magnesium stearate (claim 70); and
the binder is lactose (claim 68) and HPMC.
Snyder et al teach “pharmaceutical compositions comprising... niraparib, abiraterone acetate, and prednisone” (Paragraph 0011), wherein “[t]he compositions... may be in a form suitable for oral use, for example, as... granules” (Paragraph 0047), wherein “the niraparib [and] abiraterone acetate may be administered in a first dosage form, while the prednisone is administered to the patient in a second, separate dosage form” (Paragraph 0039). As further taught by Snyder et al, the “granules... provide the active ingredients in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives” and, optionally, “[a]dditional excipients” (Paragraph 0052).
Accordingly, it would have been prima facie obvious to formulate a composition comprising granules comprising abiraterone acetate, niraparib and a pharmaceutical carrier(s).
However, the granule composition taught by Snyder et al differs from the instantly claimed invention in that:
(a) Snyder et al teach the inclusion of niraparib as opposed to niraparib tosylate monohydrate; and
(b) Snyder et al do not specifically disclose any embodiments of granules and, in particular, granules comprising:
the wetting agent sodium lauryl sulfate;
the disintegrant crospovidone;
the diluent is lactose;
the glidant colloidal anhydrous silica;
the lubricant magnesium stearate; and
the binder is lactose and HPMC.
Yet, as to (a): Hedley et al, teaching “methods of administering a PARP inhibitor to a cancer patient” (Abstract) wherein “[i]n certain embodiments, the agent is niraparib or a salt or derivative thereof” (Paragraph 0009), further teach that “the term ‘niraparib’ means any free base compound... a salt form... or a solvated or hydrated form there... individually referred to as ‘niraparib free base’, ‘niraparib tosylate’, and ‘niraparib tosylate monohydrate’, respectively” (Paragraph 0119).
Accordingly, based further on Hedley et al, it would have been prima facie obvious to utilize niraparib tosylate monohydrate in place of niraparib in the granules of Snyder et al. The simple substitution a known niraparib equivalent for niraparib is prima facie obvious.
And, as to (b): Benjamin et al, describing “solid compositions... for the oral delivery of a drug” (Paragraph 0008), more specifically “a solid composition that comprises granules” (Paragraph 0063), specifically disclose granules comprising, as pharmaceutical excipients, sodium lauryl sulfate, crospovidone, lactose, magnesium stearate, and HMPC (Paragraph 0108, Example 7 and Paragraph 0112, Example 11) wherein “[i]n some embodiments of the invention, the solid composition further comprises at least one additional pharmaceutical ingredient” (Paragraph 0054) “such as colloidal silica” (Paragraph 0055), further disclosing “Cabosil, fumed silica, available from Cabot of Tuscola, Ill, USA” (Paragraph 0096) which entails colloidal anhydrous silica.
Accordingly, based further on Benjamin et al, it would have been prima facie obvious to formulate the granules of Snyder et al utilizing sodium lauryl sulfate, crospovidone, lactose, colloidal anhydrous silica, and magnesium stearate, and HMPC as pharmaceutical excipients. The picking and choosing of known pharmaceutical excipients (which are known to be useful in formulating granules in oral compositions) for formulating granules in oral compositions is prima facie obvious.
In view of all of the foregoing, claims 65-70 are rejected as prima facie obvious.
Claim 97 is drawn to the granule composition of claim 65, wherein the disintegrant crospovidone is present in the granule composition in a percentage from about 2 to 10% (w/w).
The final blend of Example 7 taught by Benjamin et al comprises 8.75% w/w crospovidone.
As such, claim 97 is also rejected as prima facie obvious.
Claim 98 is drawn to the granule composition of claim 65, wherein the granule composition has an immediate release profile.
Although Benjamin et al teach that, in some “embodiments, the solid dosage form is encapsulated... in a suitable pharmaceutical coating material... not limited to, sustained-release materials” and the like (Paragraph 0012), the embodied compositions of Benjamin et al and, in particular, Example 7, contain no sustained-release coating.
Accordingly, it is understood that Benjamin et al teach granule compositions having an immediate release profile.
As such, claim 98 is also rejected as prima facie obvious.
Claim 71 is rejected under 35 U.S.C. 103(a) as being unpatentable over Snyder et al (US 2018/0296574; of record) in view of Hedley et al (US 2018/0311224; of record) and Benjamin et al (US 2016/0015816; of record) as applied to claims 65-70 and 97-98 above, in further view of De Simone et al (J Drug Deliv Sci Tech 513-520, 2019; of record).
Claim 71 is drawn to the composition of claim 66, wherein the binder is HPMC 2910 15 mPa.s.
As discussed above, Snyder et al in view of Hedley et al and Benjamin et al teach a granule composition of claim 66 comprising HPMC as a binder.
However, Benjamin et al further disclose “HPMC (METHOCEL E3 LV, USP, Dow Chemical Co., Midland, Mich., USA)” (Paragraph 0102) – having a viscosity of about 3 mPa.s – as opposed to HPMC 2910 15 mPa.s as recited by claim 71.
Yet, as stated by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454 (CCPA): “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation…” Indeed, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the viscosity of HPMC as a binder in granules is clearly a result-effective variable as taught by De Simone et al, stating that “HPMC is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules)” (Abstract) and “HMPC concentration and its viscosity grade... are the most important formulation variables to modulate the drug release profile from the HPMC-based matrices according to the therapeutic needs” (Page 513, Column 2).
Accordingly, it would have been customary for an artisan of ordinary skill in the art to select a specific HPMC having a desired viscosity to function as a binder in the granules of the prior art “according to the therapeutic needs”.
As such, claim 71 is also rejected as prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 65-71 and 97-98 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending Application No. 18/833,519.
Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘519 claims are drawn to methods administering “a drug product comprising a two-drug combination of... niraparib and... abiraterone acetate” (claim 14), more specifically niraparib tosylate monohydrate (claim 23) as granules comprising each of the recited pharmaceutically acceptable excipients (claim 25).
It would have been obvious to formulate the granule dosage forms of the ‘519 application in order to carry out the method recited by the claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
The new ground(s) of rejection presented in this Office action are necessitated by Applicant’s amendments to the claims. 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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