DETAILED ACTION
Status of Application
The response filed 02/02/2026 has been received, entered and carefully considered. There are no claim amendments.
Applicant had previously elected Group I in response to restriction requirement.
Claims 14-22 are withdrawn being drawn to a non-elected invention.
Claims 1-22 are pending.
Claims 1-13 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Standing Grounds of Rejection
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-7, 11-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Levijoki et al. (U.S. Pat. Pub. 2016/0206555) as evidenced by Rowe et al. (Edetic Acid).
Rejection:
Levijoki et al. teaches an aqueous pharmaceutical composition comprising a selective D2 family dopamine agonist like ropinirole; and teaches formulations with ropinirole in aqueous solution at about 5.7% with excipients including edetate disodium (also Known as EDTA/edetic acid, see formulation of Example 9-12,
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) which are sterilized (sterile water, abstract, [14-15, 24, 41-45], claims 5, 19-20, 23-24, see full document specifically areas cited); and edetate disodium is a known chelator/scavenger of iron as established/evidenced by Rowe (edetic acid, also known as EDTA, Col. 1 second to last paragraph). As the solution contains the recited structural components of ropinirole in water as claimed are met, the desired results and properties are met such as the stability to degradation/impurity B are met as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope. As the instant specification addresses that the trace amount of iron can be 86ppb/10ml of ropinirole HCI with water (34.2mg/ml)- which is 8.6ppb per ml (e.g. instant experiment 1-3) and 330ppb/10ml of ropinirole HCI with water (34.2mg/ml)- which is 33ppb per ml (e.g. instant experiment 4); the amount of trace iron in the 1ml formulation in examples 9-12 of Levijoki et al. would inherently be below the ranged claims as it would be about 8.6ppb to about 33ppb in the 1ml as demonstrated by the instant specification and within the claimed range. Additionally, none of the components contain iron as part of their structure (ropinirole and water do not contain iron in the structure, neither does tartaric acid, EDTA, sodium CMC, nor HCl/NaOH), wherein the trace amount or iron would be expected to fall within the claimed range as demonstrated by the instant specification. It is noted that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342,1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). An inherent feature need not be recognized at the time of the invention. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. The fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.
All the critical elements are taught by the cited reference and thus the claims are anticipated.
Response to Arguments:
Applicant's arguments are centered on the assertion that Levijoki does not disclose the iron concentration of the ropinirole formulations, that the examples of the instant specification cannot be extrapolated to other formulations with different ropinirole concentrations and different compositions as the instant specification examples contains 34.2mg/ml ropinirole HCl and Levijoki contains 57mg/ml ropinirole HCl which is 1.7x more than the instant examples, that it is inappropriate to assume that the examples of Levijoki will have 10 times less iron based on a decrease in volume, that the presence of EDTA with trace iron would sill constitute iron.
This is fully considered but not persuasive.
While Levijoki does not disclose the iron concentration of the ropinirole formulations, the solution contains the recited structural components of ropinirole in water as claimed are met, the desired results and properties are met such as the trace amount of iron and stability to degradation/impurity B are met as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope. The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer; wherein the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable as there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Applicant has not presented any evidence that the prior art does not have the recited trace levels of iron claimed.
As for the assertion that the specification examples cannot be extrapolated to other formulations with different concentrations/compositions as the amount of ropinirole in the prior art is 1.7x that of the instant examples, this is fully considered but not persuasive. The instant specification examples demonstrate that the amount of trace iron without the scavenger treatment and filtration would range from 8.6ppb per ml (86ppb/10ml of aqueous solution of ropinirole HCI (34.2mg/ml)) to 33ppb per ml (330ppb/10ml of aqueous solution of ropinirole HCI (34.2mg/ml)) which is a fraction of the claimed range and as the structural components of the claim are met (water and 1-15%wt ropinirole) the recited properties are met. As for the assertion that the concentrations of the prior art are 1.7x that of the instant examples, this is not persuasive as even if the amount of ropinirole is 1.7x the instant examples (i.e. 8.6-33ppb per ml x1.7=about 14.62-56.1ppb/ml)l, the amount of trace iron is inherently less than the range claimed absent evidence to the contrary.
As for the assertion that it is inappropriate to assume that the examples of Levijoki will have 10 times less iron based on a decrease in volume, this is not persuasive as the trace amount of iron in the instant examples is based on 10ml of solution wherein the concentration of trace iron per ml is 8.6-33 ppb per ml wherein contrary to Applicant’s assertion that volume not a consideration - 1ml of the instant exemplified solutions would be 8.6-33 ppb not 86-330ppb, and as the prior art of Levijoki is also for 1ml (i.e. 8.6-33 ppb trace iron), the amount of trace iron would fall within the claimed range.
As for the assertion that the presence of EDTA with trace iron would still constitute iron this is fully considered and persuasive but does not overcome the prior art rejection as the prior art solution contains the recited structural components of ropinirole in water as claimed are met, the desired results and properties are met such as the trace amount of iron and stability to degradation/impurity B are met as any component that materially affects the composition and its properties would have to be present in the claim to be commensurate in scope.
Accordingly, the rejection stands.
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 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Levijoki et al. (U.S. Pat. Pub. 2016/0206555) as evidenced by Rowe et al. (Edetic Acid) as applied to claims 1-7, 11-13 above.
Rejection:
The teachings of Levijoki et al. as evidenced by Rowe et al. are addressed above.
Levijoki et al. as evidenced by Rowe et al. does not expressly exemplify the ranges recited but does teach that the ropinirole or its pharmaceutical salt can be from about 0.2-about 10% more typically from 0.3-8% [25] and about 90-99.8% of sterile water [25-26].
While Levijoki et al. as evidenced by Rowe et al. does not teach the exact claimed values for the sterile water but they are embraced (instant claim 8-9) or overlap the taught ranges (instant claim 10); wherein it would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize within the taught range to attain the desired therapeutic profile and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality for the claimed values.
Response to Arguments:
Applicant's arguments are those directed to Levijoki which is addressed above.
Accordingly, the rejection stands.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Schmitz et al. (U.S. Pat. Pub. 2014/0275202).
Rejection:
Schmitz et al. teaches an aqueous composition comprising ropinirole with excipients like buffers and antioxidants to reduce impurities and improve stability with a pH from about 3.0-about 6.5 (abstract, [51]). The composition contains excipients to achieve a desired pH and stability (has stability to pH (has buffers), also has stability to impurities e.g. low or no impurities like compound/impurity B (4-[2-(dipropylamino) ethyl]indoline-2,3-dione hydrochloride, can be less than 3% and less than 2% and less than 1%) ([53, 55-56], includes amounts like 0.04% 0.01%, 0.001%, zero and near zero). The aqueous solvent includes sterile water [51]. composition is for injection, the antioxidants include one or more of sequestering agents like citric acid, ascorbic acid, and sodium citrate [71]. The antioxidant can be from about 0.1, about 5% up for about 20% [71]. The ropinirole can be from 0.05mg/ml-133mg/ml (about 0.005-about 13.3%) [15] and exemplified at 1.5%wt/v with a volume of 1ml (Table A, Example 2-3 [68, 91-93]). Schmitz et al. exemplifies that formulation with antioxidants like citrate buffered formulations have little to no impurity of compound B at a month like the instant specification which addresses that the iron content corresponds with the degradation rate of ropinirole (amount of impurity B, Table F) wherein it is implicit if not prima facie obvious that the amount of trace iron would fall within the recited ranges as the solution contains the recited structural components of ropinirole in water as claimed and exemplified at 1ml, the desired results and properties are present as demonstrated/evidenced by instant specification for the correspondence of trace iron to the impurity B with a reasonable expectation of success.
While prior art does not teach the exact claimed values for ropinirole and water for the instant dependent claims they are embraced (ropinirole about 0.005-about 13.3%, sterile water about ropinirole about 99.99%-about 86.7%) wherein it would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize within the taught ranges to attain the desired therapeutic profile and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality for the claimed values.
Response to Arguments:
Applicant's arguments center on the assertion that there is no evidence that the prior art formulation necessarily contain less than 140ppb of trace iron and that Schmitz is silent on the amount of iron, there is no motivation to modify the prior art to have less than 140 ppb of iron, that while the iron content in the solution corresponds with the degradation rate of ropinirole (Impurity B) the specification does not suggest that a ropinirole composition with low degradation to Impurity B necessarily has low iron concentrations wherein the Office has failed to meet the burden of inherency of the Schmitz disclosure, that the specification defines “stable aqueous pharmaceutical composition” to be
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and that Schmitz only reports for up to 6 months with impurity level of 0.7% and 1.26% at 6 months which is higher than Applicant’s formulation at 36 months for batch B-E of 0.587% to 0.712%.
This is fully considered but not persuasive.
With regards to the assertion that there is no evidence that the prior art formulation necessarily contain less than 140ppb of trace iron and that Schmitz is silent on the amount of iron this is not persuasive as Schmitz et al. teaches a ropinirole composition comprising water with little to no impurity of compound B wherein the prior art does not need to recite the amount of trace iron which the instant specification addresses that the iron content corresponds with the degradation rate of ropinirole (amount of impurity B); then by default a ropinirole composition with low degradation to Impurity B cannot have a high concentration of trace iron – it must have a level of trace iron that is low enough to have a low degradation rate, wherein it is implicit if not prima facie obvious that the amount of trace iron would fall within the recited ranges as the solution contains the recited structural components of ropinirole in water as claimed and exemplified at 1ml, the desired results and properties are present as demonstrated/evidenced by instant specification for the correspondence of trace iron to the impurity B with a reasonable expectation of success absent evidence to the contrary which has not been presented.
With the assertion that there is no motivation to modify the prior art to have less than 140 ppb of iron, this is not persuasive as the modification of the rejection is to the exact claimed values for ropinirole and water for the instant dependent claims which are embraced by the teachings of the prior art wherein it would be prima facie obvious to one of ordinary skill in the art to optimize within the taught ranges to attain the desired therapeutic profile and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality for the claimed values.
As for the assertion that the Office has failed to meet the burden of inherency of the Schmitz disclosure as while the iron content in the solution corresponds with the degradation rate of ropinirole (Impurity B) the specification does not suggest that a ropinirole composition with low degradation to Impurity B necessarily has low iron concentrations, this is not persuasive. The rejection is not anticipation/inherency, and as the specification addresses that the iron content in the solution corresponds with the degradation rate of ropinirole (Impurity B); then by default a ropinirole composition with low degradation to Impurity B cannot have a high concentration of trace iron – it must have a level of trace iron that is low enough to have a low degradation rate, wherein as addressed above it is implicit if not prima facie obvious that the amount of trace iron would fall within the recited ranges as the solution contains the recited structural components of ropinirole in water as claimed and exemplified at 1ml, wherein desired results and properties are present as demonstrated/evidenced by instant specification for the correspondence of trace iron to the impurity B with a reasonable expectation of success absent evidence to the contrary.
As for the assertion that the specification defines “stable aqueous pharmaceutical composition” to be
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and that Schmitz only reports for up to 6 months with impurity level of 0.7% and 1.26% at 6 months which is higher than Applicant’s formulation at 36 months for batch B-E of 0.587% to 0.712%. This is not persuasive and not representative of the prior art of Schmitz. Table D demonstrates the impact of pH on the formulation where the teaching for Schmitz is for the formulation to be at a pH of about 3.0-about 6.5 and the impurity level for compound B cited by Applicant at 1.26% at 6 months with a pH of 7 is not for the teaching of Schmitz but to demonstrate a pH outside the range. The levels for the Schmitz solutions such as the pH of 4.4 is 0.7% at 6 months which are stable and the teaching of Schmitz is for impurities in the formulations can be less than 2% and less than 1% [56] which would apply under various conditions including the instant recited conditions - as the prior art establishes that the compositions are stable and with a low level of impurities. Please note, since the Office does not have the facilities for examining and comparing Applicants’ composition with the composition of the prior art, the burden is on applicant to show a novel or unobvious difference between the claimed product and the product of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), and "as a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith." In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
It is noted that Applicant’s argument for long term stability for the claimed composition is not supported by Applicant’s own data as Batch A in Table 1 has 184ppb trace iron and considered a “stable aqueous pharmaceutical composition” as it has less than 2% of impurity B at 36 months under the recited conditions demonstrating that compositions with more than 140ppb trace iron are also stable.
Accordingly, the rejection stands.
Conclusion
Claims 1-13 are rejected.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613
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