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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12 January 2026 has been entered.
Applicant’s amendment of 12 January 2026, in which claims 1, 10, 16 have been amended, is acknowledged.
Claims 1, 2, 6-12, 14-17 are pending in the instant application.
Claims 1, 2, 6-12, 14-17 are examined herein.
Response to arguments of 12 January 2026
On 12 January 2026, Applicant has amended independent claims 1, 10, 16 by deleting the recitation “no more than 10% w/v” propylene glycol in a liquid pharmaceutical composition of ropinirole. As a result, the rejection of claims 1, 2, 6-12, 14-17 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description/new matter, is herein withdrawn.
A new rejection is made below, based on Applicant’s amendment of 12 January 2026.
Applicant’s arguments (Remarks of 12 January 2026, pages 4-6) against the rejection of claims 1, 2, 6-12, 14-17 under AIA 35 U.S.C. 103 over Schmitz, in view of King and Barr, have been considered.
Applicant argues (page 4, paragraphs 6-7 under Remarks) that King does not teach propylene glycol, rather King only teaches esters of propylene glycol. In response, the paragraph in King (column 3, lines 14-18) lists oily esters, for example esters of glycerine,
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and also lists glycerine, water, saline, ethyl alcohol or propylene glycol as vehicles.
Irrespective whether King refers to propylene glycol as vehicle, or to esters as vehicle, Barr clearly teaches the advantages of using aqueous solutions of sorbitol and propylene glycol as carriers for oral pharmaceutical formulations.
The rejection is made over the combined teachings of Schmitz, who teaches liquid formulations of ropinirole hydrochloride comprising water as carrier and a citrate buffer; King, who teaches ropinirole or a pharmaceutically acceptable salt thereof for oral administration as liquid formulation containing conventional additives such as, for example, sorbitol, as well as aqueous or non-aqueous vehicles, for example water or propylene glycol/or esters thereof; and Barr, who teaches the advantages of using aqueous solutions of sorbitol and propylene glycol as carriers for oral pharmaceutical formulations. Thus, the teachings of Barr provide the motivation to add water, sorbitol and propylene glycol as carriers to ropinirole, in order to obtain a liquid oral pharmaceutical composition.
Applicant argues (page 4, paragraph 8 under Remarks) that Barr’s teaching is “a teaching of biological stability and is not a teaching of chemical stability”.
In response, regarding Applicant’s argument related to the stability of formulations, stability is a property of the composition. Schmitz, King and Barr render instant composition obvious; the property of such a claimed composition will also be rendered obvious by the prior art teachings, since the properties are inseparable from its composition. Therefore, if the prior art teaches the composition or renders the composition obvious, then the properties/stability are also taught or rendered obvious by the prior art. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990.) See MPEP 2112.01. The burden is shifted to Applicant to show that the prior art product does not possess or render obvious the same properties as the instantly claimed product.
Applicant (page 4, last paragraph, page 5, first paragraph) refers to the Declaration under 37 CFR 1.132 signed by Francesca Minale, co-inventor, submitted on 8 November 2023, which had been considered on 26 March 2024. Applicant argues unexpected results with the compositions of the present invention.
Applicant argues (Remarks of 12 January 2026, page 4, last paragraph, page 5, first paragraph) that a carrier consisting of water, propylene glycol and sorbitol (Formulation #21) reduce chemical degradation of the ropinirole compound better than a carrier consisting of water, glycerin, propylene glycol and sorbitol (Formulation #19) or a carrier consisting of water, glycerin and sorbitol (Formulation #20). See Table 8 of the 1.132 declaration. Specifically, a formulation containing the claimed carrier contained 4.5 times less degradants of ropinirole after storage at 60 degrees Celsius for 3 weeks than a formulation containing glycerin instead of propylene glycol and 6 times less degradants than a formulation containing glycerin in addition to the triple combination. Nothing in the prior art suggests that this specific triple combination would provide the best stability results.
In response, Table 8 in the Minale Declaration compares the relative stabilities of ropinirole formulation #21, which contains a mixture of water, propylene glycol and sorbitol as carrier (as in instant the instant claims), with similar formulations containing glycerin (formulations #19, #20). It is unclear how such a comparison is relevant to the rejection on record, and why such a comparison represents unexpected results.
Applicant argues (page 5, third paragraph) that chemical stability and biological stability are different, and Barr is irrelevant because Barr “only teaches biological stability”. This argument is not persuasive, because (1) there is no reference to biological or chemical stability in the instant claims, and (2) as indicated above, stability is an inherent property of the composition (In re Spada).
Applicant argues (page 5, last two paragraphs, page 6, first paragraph) that only Schmitz and King are relevant because only Schmitz and King teach ropinirole compositions, and King teaches water, sorbitol, propylene glycol as being interchangeable in ropinirole formulations. Applicant argues unexpected results with a triple combination of water, sorbitol and propylene glycol as carriers, compared to a triple combination of water, glycerin and sorbitol, or to a quadruple combination of water, propylene glycol, glycerin and sorbitol.
This argument is not persuasive. Barr teaches the advantages of using aqueous solutions of sorbitol and propylene glycol as carriers for oral pharmaceutical formulations. A person of ordinary skill in the art would prepare an oral composition of ropinirole using aqueous solutions of sorbitol and propylene glycol as carriers, with a reasonable expectation of success.
For these reasons, the rejection of claims 1, 2, 6-12, 14-17 under AIA 35 U.S.C. 103 over Schmitz, in view of King and Barr, is herein maintained and a modified rejection is made below, based on Applicant’s amendment of 12 January 2026.
Applicant’s amendment of 12 January 2026 necessitated the following new and modified rejections.
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 1, 2, 6-9, 14-17 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.
Independent claims 1, 16 recite “wherein w/v denotes weight by total volume of the composition”; yet, claims 1, 16, as amended on 12 January 2026, no longer recite “w/v” because Applicant has amended independent claims 1, 16 by deleting the recitation “no more than 10% w/v” propylene glycol in a liquid pharmaceutical composition of ropinirole.
Appropriate correction of the claim language is required.
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 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 of this title, 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 1, 2, 6-12, 14-17 are rejected under AIA 35 U.S.C. 103 as obvious over Schmitz et al. (US 2014/0275202, cited in PTO-892 of 16 September 2022), in view of King (US 6,218,421, cited in PTO-892 of 11 May 2023) and Barr et al. (J. Am. Pharm. Assoc. 1956, 46 (4), 217-218, cited in PTO-892 of 26 March 2024).
Schmitz (US 2014/0275202) teaches (Table A, page 5, also Table B, page 6) a liquid pharmaceutical composition comprising ropinirole hydrochloride, and a liquid vehicle comprising one carrier which is water and citrate buffer.
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The compositions are utilized to treat Parkinson’s disease, as in instant claims 14, 15.
The concentration of ropinirole hydrochloride in the liquid pharmaceutical composition (Table A) is 1.5% w/v; water is the only carrier in the composition (concentration over 98% w/v); the concentration of buffer citric acid in the liquid composition is 0.11% w/v and the concentration of sodium citrate is 0.14% w/v, which is within the range in instant claim 10, and within the range/close to the range in instant claim 12.
Schmitz teaches [0050] that the concentration of ropinirole in the composition is 1 mg/mL (0.1 % w/v) to 133 mg/mL, which overlaps with the range in instant claim 10. Schmitz further teaches that ropinirole can be present in the composition in an amount of 0.05, 0.5 or 1 mg/mL, which are within the range in instant claims 10, 11.
Schmitz teaches [0062] methyl, ethyl, propyl, or butyl paraben as antimicrobial agents in the liquid composition, as in instant claims 8, 9, 16, 17.
Schmitz teaches [0051] that ropinirole can be mixed with a suitable aqueous solvent that dilutes, dissolves and/or suspends ropinirole, such as sterile water.
Schmitz also teaches [0052] that ropinirole can be mixed with a suitable non-aqueous pharmaceutical solvent (safe and non-toxic for administration to humans) that dilutes, dissolves and/or suspends ropinirole.
Schmitz does not teach a mixture of water, propylene glycol and sorbitol as liquid carriers in the pharmaceutical composition, as in instant claims.
Schmitz does not specifically teach that the concentration of ropinirole in the liquid composition is 0.01% to 0.05% w/v, as in instant claims 10, 11, and that the concentration of water is 10% to 90% w/v, as in instant claims 10-12.
Schmitz teaches injectable compositions of ropinirole.
Schmitz does not teach that the formulations of ropinirole are for oral administration, as in the instant claims.
King (US 6,218,421) teaches (column 2, lines 13-17) ropinirole or a pharmaceutically acceptable salt thereof, formulated for administration by any route, including oral, or parenteral/iv injectable.
King teaches (column 3, lines 5-20) ropinirole for oral administration as liquid formulations. Such liquid formulations contain conventional additives such as, for example, sorbitol, syrup; aqueous or non-aqueous vehicles, for example propylene glycol, water; preservatives.
Barr et al. (J. Am. Pharm. Assoc. 1956, 46 (4), 217-218) teach (page 218, left column, second paragraph, also page 217, left column, first paragraph) the use of aqueous solutions of propylene glycol and sorbitol as carriers in oral pharmaceutical formulations. Barr teaches (page 218, left column, second paragraph) that propylene glycol is a very good solvent, yet if only propylene glycol is used in formulations, one encounters objections based on its taste.
Barr teaches (page 217, left column, first paragraph) that sorbitol is a sugar alcohol/polyol used in pharmaceutical product formulations; yet most sugars and polyols commonly employed in product formulation including sorbitol support the growth of microorganisms.
Barr teaches (page 218, left column, first paragraph) that propylene glycol has a significant and useful preservative activity in solutions of sorbitol.
Barr prepares (page 217, left column, last paragraph) aqueous solutions of sorbitol in propylene glycol-water in a concentration of 0 to 70% w/v using gradations of 10%.
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The aqueous solutions prepared by Barr (Table II, lines 2-3) are carriers consisting of water, sorbitol and propylene glycol, as in instant claims, and are carriers consisting of 10% to 90% w/v water, propylene glycol and sorbitol, as in instant claims 10-12.
Barr teaches (Table II) that as little as 10% w/v propylene glycol added to water (0% sorbitol, first line in Table II, corresponding to a carrier consisting of water and propylene glycol, as in instant claim 1), or to sorbitol solutions of low concentration (10 % or 20% sorbitol, lines 2-3 in Table II, corresponding to a carrier consisting of water, sorbitol and propylene glycol, as in instant claim 10), resulted in the inhibition of bacteria and most molds.
Barr teaches (page 218, left column, second paragraph) that sorbitol and propylene glycol complement each other: the unpleasant taste of oral liquid pharmaceutical formulations containing only propylene glycol and water is remedied by adding sorbitol, and the microbial growth associated with sorbitol is reduced by adding propylene glycol, which acts as a preservative in sorbitol aqueous solutions (page 218, right column, point 5).
It would have been obvious to a person of ordinary skill in the art to combine the teachings of Schmitz, King and Barr to arrive at the instantly claimed invention. The person of ordinary skill in the art would have been motivated to formulate ropinirole or its HCl salt as a liquid oral pharmaceutical composition wherein the carrier consists of water, propylene glycol and sorbitol, because King teaches ropinirole or a pharmaceutically acceptable salt thereof for oral administration as liquid formulation containing conventional additives such as, for example, sorbitol; as well as aqueous or non-aqueous vehicles, for example propylene glycol, or water; and Barr teaches the advantages of using aqueous solutions of sorbitol and propylene glycol as carriers for oral pharmaceutical formulations. Thus, the person of ordinary skill in the art would have used an aqueous solution of sorbitol and propylene glycol as carrier to formulate ropinirole or its HCl salt as a liquid oral pharmaceutical composition, with the expectation that said carrier dissolves ropinirole hydrochloride and the resulting liquid formulation retains therapeutic effect and is suitable for oral administration. Further, the person of ordinary skill in the art would have used an aqueous solution of sorbitol and propylene glycol as carrier to formulate ropinirole or its HCl salt as a liquid oral pharmaceutical composition, with the expectation that sorbitol remedies the poor taste of aqueous propylene glycol solutions and propylene glycol acts as a preservative in sorbitol aqueous solutions of ropinirole.
With respect to claims 6-7, 12, the person of ordinary skill in the art would have been motivated to add a citrate buffer to such a formulation, because Schmitz teaches liquid formulations of ropinirole hydrochloride comprising water as carrier and a buffer which is a mixture of citric acid and sodium citrate. Thus, the person of ordinary skill in the art would have added a buffer such as citrate to a liquid formulation of ropinirole hydrochloride, with the expectation that the resulting mixture retains therapeutic effect.
With respect to claims 8, 9, 16-17, the person of ordinary skill in the art would have added parabens to the liquid composition, because Schmitz teaches parabens as antimicrobial additives in the composition to improve stability.
With respect to claims 10-11, the person of ordinary skill in the art would have used a concentration of ropinirole hydrochloride such as 0.02% w/v in the liquid formulation, because Schmitz teaches liquid formulations containing 0.05, 0.5, 1 mg/mL of ropinirole or salt thereof. It is well within the skill of the art to determine the effective amount within a range through routine experimentation. It is noted that "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955.)
With respect to claims 10-12, the person of ordinary skill in the art would have varied the relative amount of water/propylene glycol/sorbitol in the liquid composition of ropinirole hydrochloride, and would added different relative amounts of citric acid/citrate in order to adjust the pH of the liquid composition, with the aim of optimizing the properties/stability of the formulation. Such an optimization of relative ratios of water/propylene glycol/sorbitol carriers to buffer citrate is part of routine experimentation, in the absence of some evidence of the criticality of the claimed ranges.
As such, claims 1, 2, 6-12, 14-17 are rejected as prima facie obvious.
Conclusion
Claims 1, 2, 6-12, 14-17 are rejected.
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/IRINA NEAGU/Primary Examiner, Art Unit 1629