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 .
Status of Application
The Amendments and Remarks filed on 06/16/26 are acknowledged.
Claims 7 and 9-10 were cancelled.
Claims 1-2 and 4-6 were amended.
Claims 1-6, 8, and 11-40 are pending.
Claims 17-40 were previously withdrawn from consideration.
Claims 1-6, 8, and 11-16 are included in the prosecution.
Response to Amendments/Arguments
Claim Objections
In light of the cancellation of claim 9, the objection to this claim is moot. The correct spelling of “oxybutynin” in amended claim 1 is acknowledged.
However, claim 2 is objected to, necessitated by Applicant’s amendment.
Rejection of claims under 35 USC § 112(d)
In light of the cancellation of claim 7, the rejection of this claim under 35 U.S.C. 112(d) is moot.
In light of the amendment of claims 5 and 6, the rejection of these claims under 35 U.S.C. 112(d) is withdrawn.
Rejection of claims under 35 USC §§ 102(a)(1) and 103
In light of the amendment of claim 1 to recite that the polymer carrier comprises poly(lactide-co-glycolide) (PLGA), Applicant’s arguments (Pages 9-13, filed 06/16/26) regarding the following prior art rejections have been fully considered and are persuasive.
Rejection of claims 1-8 and 11-13 under 35 U.S.C. 102(a)(1) as being anticipated by Na et al. (CA 3 167 978 A1 – “Na”)
Rejection of claims 1-2, 4-11, 13, and 16 under 35 U.S.C. 102(a)(1) as being anticipated by Sanders et al. (US 2002/0147236 A1 – “Sanders”)
Rejection of claims 14 and 15 under 35 U.S.C. 103 as being unpatentable over Sanders, as applied to claims 1-2, 4-11, 13, and 16, in view of Bielski et al. (US 2019/0125687 A1 – “Bielski”) and Dash et al. (Journal of Pediatric Surgery 51 (2016) 2025-2029 – “Dash”)
Since the cited references do not teach or suggest a combination of PLGA with the specific active agents now recited in amended claim 1, the rejections listed above are withdrawn.
However, upon further consideration of the amended claims, a new ground(s) of rejection is made over Zhang (US 2008/0260846 A1).
Since the new grounds of rejection were necessitated by Applicant’s amendment, this action is made FINAL.
Claim Objections
Claim 2 is objected to because of the following informalities: In claim 2, line 2, the acronym “PLA” should be spelled out at “polylactide.” Appropriate correction is required.
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.
Claim 2 is 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 pre-AIA the applicant regards as the invention.
Claim 2 recites the limitation "… wherein the polymer carrier comprises PLGA and PLA." Claim 2 is dependent on claim 1, and claim 1 recites that the polymer carrier comprises poly(lactide-co-glycolide) (PLGA). Claim 1 does not recite that the polymer carrier is selected from a group comprising PLGA and PLA. It is recommended that either claim 1 be amended to recite a Markush group of polymer carriers which includes PLGA and PLA or claim 2 be amended to recite that the polymer carrier further comprises PLA.
Notice for all US Patent Applications filed on or after March 16, 2013
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.
New Rejections Necessitated by Amendment
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 1-2, 4-6, 11, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (US 2008/0260846 A1).
Instant claim 1 is drawn to a microsphere for controlled long-term sustained delivery of an active agent, comprising the active agent and a polymer carrier that encapsulates the active agent, wherein the active agent comprises oxybutynin, tolterodine, solifenacin, darifenacin, pramipexole, or tamsulosin, or a free base, a stereoisomer, a derivative, an analog, a prodrug, or a pharmaceutically acceptable salt thereof,
wherein the polymer carrier comprises poly(lactide-co-glycolide) (PLGA), and
wherein the microsphere has a zero-order release when contacting with an aqueous phase, with a coefficient of determination (R2) of at least 0.99.
Zhang teaches a long-acting sustained release dosage form for treatment of Parkinson Disease, comprising a dopamine receptor agonist and a pharmaceutically acceptable biodegradable polymer, wherein the content of the dopamine receptor agonist in the sustained-release dosage form is 5-50% by weight (Abstract, claim 22). The dosage form is injectable sustained-release microspheres ([0001], [0079]-[0089], Examples 1-19 - [0111]-[0128], Examples 24-28 – [0162]-[0175], and claim 25). The active agent is the dopamine receptor agonist pramipexole ([0015], [0022], [0051], [0053], Example 17 – [0126], and claims 22-23 and 32-34). Example 17 discloses microspheres having 15% drug and a particle diameter of 1-250 micrometers by using 0.15 g of pramipexole and 0.85 g of poly(lactide-glycolide) (PLGA) (lactide : glycolide = 50 : 50) ([0126]).
Regarding instant claim 1, the limitation of a microsphere for controlled long-term sustained delivery of an active agent, comprising the active agent and a polymer carrier that encapsulates the active agent, wherein the active agent comprises pramipexole or a free base, a stereoisomer, a derivative, an analog, a prodrug, or a pharmaceutically acceptable salt thereof, and the polymer carrier comprises PLGA is anticipated by Example 17 which discloses microspheres having 15% drug and a particle diameter of 1-250 micrometers by using 0.15 g of pramipexole and 0.85 g of poly(lactide-glycolide) (PLGA) (lactide : glycolide = 50 : 50) ([0126]), as taught by Zhang. The limitation of the microsphere having a zero-order release when contacting with an aqueous phase, with a coefficient of determination (R2) of at least 0.99 is an inherent property of the microsphere and inseparable from it. Please see MPEP 2112.01. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990.) 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.
Regarding instant claim 2, the limitation of the polymer carrier comprising PLGA and PLA is anticipated by the biodegradable polymer selected from poly(lactide-glycolide), polylactic acid, etc., or a combination of two of them ([0016], [0019], [0068]), and claims 24 and 26), as taught by Zhang.
Regarding instant claim 4, the limitation of the microsphere comprising from 5% (w/w) to 50% (w/w) of the active agent by weight of the microsphere is anticipated by the microspheres having 15% drug which is 0.15 g of pramipexole (Example 17 – [0126]), as taught by Zhang.
Regarding instant claim 5, the limitations of the polymer carrier comprising PLGA having a lactide-to-glycolide ratio of about 75:25 and an intrinsic viscosity of about 0.2 dL/g are anticipated by the PLGA having a lactide to glycolide ratio of 75:25 ([0020], [0069], Example 14 – [0114], and claim 28), as taught by Zhang. According to MPEP 2131.03 (II), prior art which teaches a range touching the claimed range anticipates if the prior art range discloses the claimed range with “sufficient specificity.” The limitation of the intrinsic viscosity of about 0.2 dL/g is an inherent or intrinsic property of the PLGA having the lactide to glycolide ratio of about 75:25 disclosed by Zhang. Please see MPEP 2112.01. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990.) 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.
Regarding instant claim 6, the limitations of the polymer carrier comprising PLGA having a lactide-to-glycolide ratio of about 50:50 and an intrinsic viscosity of about 0.2 dL/g are anticipated by the PLGA having a lactide to glycolide ratio of 50:50 ([0069], Example 17 – [0126]), as taught by Zhang. According to MPEP 2131.03 (I), a specific example in the prior art which is within a claimed range anticipates the range. The limitation of the intrinsic viscosity of about 0.2 dL/g is an inherent or intrinsic property of the PLGA having the lactide to glycolide ratio of about 50:50 disclosed by Zhang. Please see MPEP 2112.01. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990.) 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.
Regarding instant claim 11, the limitation of a composition comprising the microsphere of claim 1 is anticipated by the injectable sustained-release microspheres, injectable gels and implants ([0049]), as taught by Zhang.
Regarding instant claim 16, the limitation of an implant is anticipated by the implants ([0049]), as taught by Zhang.
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 3 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US 2008/0260846 A1), as applied to claims 1-6, 11, and 16 above.
Instant claim 3 is drawn to the microsphere of claim 1, wherein the microsphere has a diameter of from about 8 µm to about 75 µm.
The teaching of Zhang is discussed above.
Although Zhang teaches microspheres having an overlapping particle diameter range of 1-250 micrometers ([0126]), Zhang does not expressly teach a particle diameter of about 8 µm to about 75 µm.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare microspheres having 15% drug and a particle diameter of 1-250 micrometers by using 0.15 g of pramipexole and 0.85 g of poly(lactide-glycolide) (PLGA) (lactide : glycolide = 50 : 50), as taught by Zhang, and prepare microspheres with different particle diameters within the range of 1-250 micrometers, as taught by Zhang, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because 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.”
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claim 3, the limitation of the microsphere having a diameter of from about 8 µm to about 75 µm would have been obvious over the microspheres having an overlapping particle diameter range of 1-250 micrometers ([0126]), as taught by Zhang. Please see MPEP 2144.05.
Regarding instant claim 8, the limitation of the microsphere maintaining a controlled and sustained release for a period from 1 week to 6 months would have been obvious over the continuous release of drug for more than two months ([0157]), as taught by Zhang. Please see MPEP 2144.05.
Claims 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US 2008/0260846 A1), as applied to claims 1-6, 11, and 16 above, in view of Nghiem et al. (US 2009/0004281 A1 – “Nghiem”).
Instant claim 12 is drawn to the composition of claim 11, further comprising at least one anti-cryogenic agent.
The teaching of Zhang is discussed above.
Zhang does not expressly teach at least one anti-cryogenic agent.
Nghiem teaches a multiparticulate osmotic delivery system which is a modified release composition suitable for oral administration and includes a core that includes at least one drug in combination with at least one pharmaceutically acceptable excipient (Abstract). The drug includes pramipexole ([0014], FIG. 1, [0070], [0165], Example 1 – [0394], claims 1, 2, 5, 55). The drug containing microparticles are in the form of ‘pearls’ which are manufactured by mixing drug with one or more pharmaceutical excipients, and additives such as the anti-cryogenic agent glycerine ([0246]). Excipients in the microparticle include glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, carnauba wax, microcrystalline cellulose, lactose, and mixtures thereof ([0223], claim 55). Controlled release dosage forms are disclosed ([0094]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare microspheres having 15% drug and a particle diameter of 1-250 micrometers by using 0.15 g of pramipexole and 0.85 g of poly(lactide-glycolide) (PLGA) (lactide : glycolide = 50 : 50), as taught by Zhang, in view of the microparticles comprising pramipexole, additives such as the anti-cryogenic agent glycerine and excipients such as microcrystalline cellulose and lactose, as taught by Nghiem, and produce the instant invention.
One of ordinary skill in the art would have been motivated to combine the teachings of Zhang and Nghiem because both references are drawn to microsphere or microparticle compositions containing the drug pramipexole for controlled release of the active ingredient and it is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A). One of ordinary skill in the art would have had a reasonable expectation of success in producing a functional controlled release microsphere containing pramipexole and excipients.
Regarding instant claim 12, the limitation of at least one anti-cryogenic agent would have been obvious over the anti-cryogenic agent glycerine ([0246]), as taught by Nghiem.
Regarding instant claim 13, the limitation of an excipient would have been obvious over the excipients in the microparticle including glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, carnauba wax, microcrystalline cellulose, lactose, and mixtures thereof ([0223], claim 55), as taught by Nghiem.
Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US 2008/0260846 A1), as applied to claims 1-6, 11, and 16 above, in view of Nghiem et al. (US 2009/0004281 A1 – “Nghiem”) and Chase et al. (US 2020/0147053 A1 – “Chase”).
Instant claim 14 is drawn to the composition of claim 13, further comprising an additional therapeutic agent.
The teachings of Zhang and Nghiem are discussed above.
Zhang and Nghiem do not expressly teach an additional therapeutic agent.
Chase teaches methods for treating depressive disorders by administration of an antagonist of the neurokinin receptor subtype-1 in combination with pramipexole ([0004]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare microspheres having 15% drug and a particle diameter of 1-250 micrometers by using 0.15 g of pramipexole and 0.85 g of poly(lactide-glycolide) (PLGA) (lactide : glycolide = 50 : 50), as taught by Zhang, in view of the microparticles comprising pramipexole, additives such as the anti-cryogenic agent glycerine and excipients such as microcrystalline cellulose and lactose, as taught by Nghiem, combine the pramipexole with an additional therapeutic agent such as an antagonist of the neurokinin receptor subtype-1, as taught by Chase, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so because Chase teaches the advantage of combining pramipexole with an additional therapeutic agent such as an antagonist of the neurokinin receptor subtype-1 for the treatment of depressive disorder ([0004]).
Regarding instant claims 14 and 15, the limitations of an additional therapeutic agent would have been obvious over the combination of pramipexole with an additional therapeutic agent such as an antagonist of the neurokinin receptor subtype-1 for the treatment of depressive disorder ([0004]), as taught by Chase.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. 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 ARADHANA SASAN whose telephone number is (571)272-9022. The examiner can normally be reached Monday to Friday from 6:30 am to 3:00 pm.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615
