DETAILED ACTION
This is an initial Office action for non-provisional application 18/537432 filed December 12, 2023, which claims foreign priority to EP22213699.6 filed December 15, 2022.
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 . 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.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Elections/Restrictions
In response to the restriction requirement dated 5/8/26, it is acknowledged that applicant elected Group I drawn to a solid dispersion comprising pimobendan encompassing claims 1-8 and 13-18 with traverse. The traversal is on the ground(s) that there is no undue search burden to examine all the presented claims. This is not found persuasive because the two inventions do, in fact, create a serious search burden for the examiner. As the invention of Group I is drawn to a drug composition and the invention of Group II is drawn to a process of preparing the drug composition, the examiner would need to search both drug formulations and methods of making if both inventions were to be examined together. Burden consists of searching CPC symbols and searching multiple databases for foreign references and literature searches. Further, a reference that would anticipate the invention of one group would not necessarily anticipate or even make obvious another group. Thus, a serious search burden does, in fact, exist and the restriction requirement is deemed proper and made FINAL.
Claim Status
Claims 1-11 and 13-18 are pending. Claims 9-11 are withdrawn. Claims 1-8 and 13-18 are drawn to the elected species.
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 5 and 17 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 claim 5 (see 3rd last line of claim), the phrase "such as" 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).
Regarding claim 17, the claim recites limitations that are enclosed within parentheses (see lines 3-4). However, it is unclear whether the subject matter within parentheses is part of the claimed invention or if it is optional. For purposes of examination, the subject matter within parentheses is being interpreted as being optional. Further, it should be noted that the Figure referred to in the parentheses is indefinite. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
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.
Claims 1, 7-8, 13-14 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Reven et al (WO 2011/042463; cited in IDS dated 12/12/23).
Regarding claim 1, Reven et al teach pharmaceutical compositions comprising poorly soluble active ingredients and hyperbranched polymers (abstract). According to Reven et al, the hyperbranched polymers provide the best solubility of the API and thus are effective stabilizing polymers (pg. 3, lines 6-7). Preferred active ingredients include pimobendan (pg. 3, line 3; pg. 6, line 2; pg. 40, example 21) in amorphous form to obtain advantages in terms of process yield and increased solubility (pg. 28, lines 5-10; pg. 30, lines 7-12).
Although Reven et al suggest the use of pimobendan as an active ingredient in an amorphous form within its compositions; it is not immediately envisaged.
It would have been obvious to select pimobendan from the list of active ingredients in Reven et al depending on the needs of a particular patient population and the desired treatment of the compositions. The court has reasoned a reasonable expectation of success in the art by stating that reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle. Sinclair & Carroll Co., 325 U.S. at 335, 65 USPQ at 301. Since all elements of the instant claims are taught in the prior art, combining the components for their intended use of treatment would have been obvious. A skilled artisan would have also been motivated to use pimobenden in amorphous from since Reven et al teach that amorphous forms of its active ingredients enhance solubility to achieve the desired pharmacological activity and dissolution profile of its compositions (see pg.1, pg. 28, lines 5-10; pg. 30, lines 7-12).
Regarding claim 7, Reven et al teach compositions comprising 2-5 wt.% pimobendan relative to the total weight of the solid dispersion (pg. 40, example 21).
Regarding claim 8, Reven et al teach its active ingredients can at least partially, but preferably completely also form a solid solution with the hyperbranched polymer allowing the constituents to become amorphous pg. 28, lines 5-10). Thus, Reven et al appear to teach compositions in which pimobendan selected from Reven’s list of suggest active ingredients can be present in 100% amorphous form, meeting the limitations of claim 8.
Regarding claim 13, Reven et al teach additional excipients can be used in its compositions (pg. 25, lines 1-10).
Regarding claim 14, Reven et al teach suitable excipients in its compositions including fillers, disintegrants or disintegrators, lubricants and sweeteners (pg. 25, lines 12-18). Note that sweeteners could be considered at least one flavor according to claim 14 since it is considered to have specific taste characteristics.
Regarding claim 18, Reven et al teach its active ingredients can at least partially, but preferably completely also form a solid solution with the hyperbranched polymer allowing the constituents to become amorphous pg. 28, lines 5-10). Thus, Reven et al appear to teach compositions in which pimobendan selected from Reven’s list of suggest active ingredients can be present in 100% amorphous form, meeting the limitations of “substantially amorphous”.
Claims 2-6 are rejected under 35 U.S.C. 103 as being unpatentable over Reven et al (WO 2011/042463; cited in IDS dated 12/12/23) in view of de Vasconcelos (US 2011/0014282; cited in attached PTO-892).
The disclosure of Reven et al is discussed above and incorporated herein.
Reven et al do not teach one or more stabilizing polymers as set forth in claims 2-6.
de Vasconcelos et al teach pharmaceutical compositions containing a solid dispersion of a poorly soluble active pharmaceutical ingredient, an amorphous carrier and a surfactant (abstract; see whole document) with improved dissolution properties (paragraph 0001). According to de Vasconcelos et al, at least part of its active pharmaceutical ingredients are in amorphous form (paragraph 0009). The amorphous carrier comprises polymers such as a cellulose derivative, starch derivative, polyethyleneglycol (PEG), polymethylacrylate, carbomer, polyvinyl acetate, povidone, crospovidone, D-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS 1000) or vinylpyrrolidone/vinylacetate copolymer (copovidone, PVP VA64) (paragraph 0054). de Vasconcelos et al teach its compositions with its amorphous carrier have desired dissolution properties and greater drug stability (paragraph 0008).
Therefore, it would have been obvious to an artisan of ordinary skill before the effective filing date of the claimed invention to utilize the stabilizing polymers recited in claims 2-6, which include crospovidone and polymethylacrylates as one of the stabilizing polymers in the pharmaceutical compositions of Reven et al. One would have been motivated to do so since de Vasconcelos et al teach such polymers are suitable for creating solid amorphous dispersions within pharmaceutical compositions for poorly soluble active ingredients and Reven et al teach pimobendan is a poorly soluble active ingredient.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Reven et al (WO 2011/042463; cited in IDS dated 12/12/23) in view of Garcia et al (WO 2017/103054; cited in IDS 12/12/23).
The disclosure of Reven et al is discussed above and incorporated herein.
Reven et al further teach its amount of carrier is preferably from about 10%-90% (pg. 23, lines, 2nd full paragraph) of the composition and pimobendan is in an amount of 2-5 wt.% relative to the total weight of the composition (pg. 40, example 21).
However, Reven et al do not teach all the components of the different options of formulations A-E as recited in claim 17.
Garcia et al teach pharmaceutical formulations comprising pimobendan with excipients such as 25-45 wt.% lactose monohydrate, 5-20 wt.% microcrystalline cellulose, 5-30 wt.% pig liver powder, 5-20 wt.% corn starch, and 4-20 wt.% yeast (abstract; pg. 9, lines 30-33—pg. 10, lines 1-5; Example 1; Table 4 on pg. 15). Further, Garcia teach that magnesium stearate can be incorporated as a lubricant in its composition (pg. 7, line 2) along with talc as a flow regulator or glidant (pg. 6, line 25) and sodium starch glycolate as a disintegrant (pg. 6, lines 30-31). Garcia et al also teach various types of starches can be incorporated in its compositions including gelatinized starch (pg. 7, lines 15-18).
Therefore, it would have been obvious to an artisan of ordinary skill before the effective filing date to include excipients such as lactose monohydrate, microcrystalline cellulose, pig liver powder, gelatinized starch, yeast, magnesium stearate, talc, and sodium starch glycolate within the compositions of Reven et al. One would have been motivated to do so with a reasonable expectation of success since Garcia et al suggest all excipients are conventional excipients in pharmaceutical compositions comprising pimobenden. In KSR v. Telefex, 82 USPQ2d 1385, 1397 (U.S. 2007), the Supreme Court has held that when there is market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person has good reason to pursue known options within his or her technical grasp. The court has reasoned a reasonable expectation of success in the art by stating that reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle. Sinclair & Carroll Co., 325 U.S. at 335, 65 USPQ at 301. Since all elements of the instant claims are taught in the prior art, combining the components for their intended use would have been obvious.
Regarding the amounts of pimobendan, stabilizing polymers and listed excipients; Garcia et al and Reven et al mostly suggest amounts of excipients in overlapping ranges with the instant claims. According to MPEP 2144.05, “In the case where 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). Further, it would have been obvious to an artisan of ordinary skill to manipulate and optimize the amounts of specific excipients. Optimization of parameters is a routine practice that would be obvious to a person of ordinary skill in the art to employ and reasonably expect success. One would have been motivated with a reasonable expectation of success to determine the optimal amounts of excipients depending on the desired characteristics of the composition and the method of making the composition. It should be noted that generally difference in concentrations do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such a concentration is critical. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Reven et al (WO 2011/042463; cited in IDS dated 12/12/23) in view of Liu et al (CN 112618505; cited in IDS dated 12/12/23).
The disclosure of Reven et al discussed above and incorporated herein.
Reven et al do not teach further active ingredients selected from ACE inhibitors, aldosterone antagonists and/or loop diuretics as set forth in claims 15-16.
Liu et al teach medicinal compositions comprising the ACE inhibitor, benazepril, and pimobendan for pets and methods of preparation thereof (abstract; whole document). According to Liu et al, both benazepril and pimobendane are used as separate medicines to control the heart failure of dogs (abstract; whole document).
Therefore, it would have been obvious to an artisan of ordinary skill to add the ACE inhibitor, benazepril, to the compositions of Reven et al containing pimobendan. One would have been motivated to do so since Liu et al teach both pimobendan and benazepril have advantageous cardiovascular outcomes in animals if used together. Further, it would have been obvious to add more than one ingredient for the same intended purpose in the compositions of Reven et al. It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06).
Conclusion
Claims 1-8 and 13-18 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHAEL E BREDEFELD whose telephone number is (571)270-5237. The examiner can normally be reached 8:00-5:00 Monday-Friday.
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/RACHAEL E BREDEFELD/Supervisory Patent Examiner, Art Unit 3786
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