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 . 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.
Claim Objections
Claim 1-7 are objected to because of the following informalities:
Claims 1-7, at the first line of each claim, recite the word “compositions”, which should be in singular form, rather than pluralized.
Claim 6, at the third line, recites the word “comprising”, which should be “comprises”.
Claim 7, at the last line, recites the word “vials” in plural form, which should be singular.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 –
Indefiniteness and Lack of Antecedent Basis
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 3-7 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 3 recites the limitation "the antioxidant" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 4 recites the limitation "the pH modifier" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 5 recites the limitation "the vehicles" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitation "the process of preparation" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitation "solution" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitation "the step (b) suspension" in line 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitation "solution" in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103 - Obviousness
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) 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Almarsson et al (US 2016/0243259 A1), in view of Puertos et al (Hosp Pharm, 2014, 49(3), 269-272) and further in view of Ying et al (US 2021/0214334 A1).
Almarsson taught pharmaceutical compositions [claim 1, ¶0010] comprising lenalidomide [0968], one or more pharmaceutically acceptable excipients [0390] and sodium chloride injection (e.g., 0.9 % sodium chloride) [¶s 0040, 1002, 1004, claim 20], formulated in liquid dosage form [0851].
Almarsson was silent an impurity less than 0.5 % after storing for 3 months at 2-8 º C, as recited in claim 1.
Puertos taught the stability and sterility of an intravenous 0.9% sodium chloride solution that had been cooled (e.g., 5.2 ºC, Tables 1-2) for an extended period of time, where the solution remained stable and showed no signs of microbial or fungal growth for a period of 199 days [abstract]. The stability of 0.9 % sodium chloride solutions enables hospitals and emergency medical service facilities to significantly extend the expiration date assigned to these fluids, and therefore save time and money and decrease the number of fluids that need to be discarded each month [page 271-272, Conclusion].
Since Almarsson taught pharmaceutical compositions comprising sodium chloride injection (e.g., 0.9 % sodium chloride), it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Almarsson, solutions cooled and stable for an extended period of time, as taught by Puertos et al [abstract and conclusion]. The ordinarily skilled artisan would have been so motivated, because the stability of compositions comprising 0.9 % sodium chloride solution enables hospitals and emergency medical service facilities to significantly extend the expiration date assigned to these fluids, and therefore save time and money and decrease the number of fluids that need to be discarded each month, as taught by Puertos [page 271-272, Conclusion].
The combined teachings of Almarsson and Puertos did not teach less than 0.5 % impurity.
Ying taught lenalidomide having a purity of more than 99.90%, maximum single impurity of less than 0.10%, which was suitable for industrial production [abstract].
Since Almarrson taught compositions comprising lenalidomide, it would have been prima facie obvious to include, within the combined teachings of Almarsson and Puertos, lenalidomide having a purity of more than 99.90%, maximum single impurity of less than 0.10%, as taught by Ying. The ordinarily skilled artisan would have been motivated to provide compositions suitable for industrial production, as taught by Ying at the abstract.
Claims 2-5 are rendered prima facie obvious because Almarsson taught butylated hydroxyanisole [claim 20, 0833]; glacial acetic acid [Table 9, page 98, listed under Intravenous]; polyethylene glycol 400 and propylene glycol [Table 9, page 99, listed under Intravenous].
Claim(s) 6 is rejected under 35 U.S.C. 103 as being unpatentable over Almarsson et al (US 2016/0243259 A1), in view of Puertos et al (Hosp Pharm, 2014, 49(3), 269-272), further in view of Ying et al (US 2021/0214334 A1) and further in view of Borovinskaya et al (US 2020/0330445 A1).
The 35 U.S.C. 103 rejection over Almarsson, Puertos and Ying was previously described.
Additionally, Almarsson taught the active ingredient at between 0.1 and 100 % [0394, 0398] and 95-100 % excipients [0827].
However, Almarsson was not specific excipients at 0.1 to 1 %, as recited in claim 6.
Nevertheless, Borovinskaya taught liquid [0011-0012] lenalidomide (1-95 % lenalidomide at [0165]) formulations [title] comprising excipients [0085, 0097-0098] (e.g., butylated hydroxyanisole [0101]; acetic acid [0086, 0097]; and, polyethylene glycol 400 and propylene glycol [0096], at 0-95 % [see each of the examples].
Since Almarsson generally taught liquid lenalidomide formulations comprising excipients, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Almarsson, excipients at 0-95 %, as taught by Borovinskaya. The ordinarily skilled artisan would have been motivated to formulate the composition.
Regarding the claim 6 limitations of the amounts of butylated hydroxyanisole and glacial acetic acid, the differences in the claimed subject matter and the prior art are 0.1 % as claimed, versus 95-100 % excipients taught by Almarsson and 0-95 % excipients taught by Borovinskaya.
Almarrson was not silent as the amounts of the excipients. For example, although Almarrson taught 95-100 % excipients, Almarrson was not as specific the claimed 0.1-1 % excipients. However, Borovinskaya taught that these ingredients are useful at 0-95 %, an amount that overlaps the amount instantly recited. These ingredients, and their amounts, are recognized to have different effects (greater or less formulation of the pharmaceutical composition; Borovinskaya at the Examples) with changing amounts used. Thus, the general condition (the concentration) is known, and the amounts of these ingredients are recognized to be result effective. As such, result effective variables can be optimized by routine experimentation, and it would have been prima facie obvious to have optimized the amounts of the excipients present in the composition of Almarrson, as taught by Borovinskaya et al. See MPEP 2144.05.
With the combined teachings of Almarrson and Borovinskaya, the ordinarily skilled artisan would have had a reasonable expectation of success, and without undue experimentation, of arriving at the claimed range of butylated hydroxyanisole and glacial acetic acid.
The instant claim 6 recites 1-5 % active agent; 0.1 to 1 % butylated hydroxyanisole and glacial acetic acid; and, 1-95 % polyethylene glycol 400 and propylene glycol.
Almarsson taught the active ingredient at between 0.1 and 100 % and 95-100 % excipients. Borovinskaya taught 1-95 % lenalidomide and 0-95 % excipients. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over Almarsson et al (US 2016/0243259 A1), in view of Puertos et al (Hosp Pharm, 2014, 49(3), 269-272), further in view of Ying et al (US 2021/0214334 A1) and further in view of Schaut et al (PDA J Pharm Sci and Tech, 2017, 71, 279-296).
The 35 U.S.C. 103 rejection over Almarsson, Puertos and Ying was previously described. The combined teachings of the prior art were silent glass vials, as recited in claim 7.
Schaut taught that glass has long been used for packaging precious liquids, in particular pharmaceuticals. Its unique combination of hermeticity, transparency, strength, and chemical durability make it the optimal material for such an important role [abstract].
Since the combined teachings of Almarsson, Puertos and Ying taught liquid pharmaceutical compositions, it would have been prima facie obvious to one of ordinary skill in the art to include, within the combined teachings of the prior art, packaging in glass vials, as taught by Schaut et al. The ordinarily skilled artisan would have been so motivated, because glass has long been used for packaging precious liquids, in particular pharmaceuticals. Its unique combination of hermeticity, transparency, strength, and chemical durability make it the optimal material for such an important role [Schaut at the abstract].
The instant claim 7 recites “wherein the process of preparation comprises the steps of a-e. The limitation of preparing the 3-(4-amino-1-oxo-1, 3 dihydro-isoindol-2-yl)-piperdine-2,6-dione is a product-by-process limitation. Product by process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.
Even though the product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.
In the instant case, the pharmaceutical of the combined teachings of the prior art (e.g., liquid compositions comprising lenalidomide and excipients) reads on the claimed pharmaceutical composition comprising 3-(4-amino-1-oxo-1, 3 dihydro-isoindol-2-yl)-piperdine-2,6-dione and excipients. As such, the patentability of the instant composition does not depend on its method of production, and the Applicant’s limitation regarding the process of preparing pharmaceutical compositions of 3-(4-amino-1-oxo-1, 3 dihydro-isoindol-2-yl)-piperdine-2,6-dione is not patentable, in view of the combined teachings of Almarsson, Puertos, Ying and Schaut et al. MPEP 2113.
Conclusion
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612