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 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.
Previous Rejections
Applicant’s arguments, filed 4/29/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claims 2-5 and 7-10 are cancelled.
Claims 1, 6, and 11-14 are pending and are examined on the merits in this prosecution.
CLAIM REJECTIONS
Obviousness Rejection
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.
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.
1) Claims 1, 6, and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Pilgaonkar (US 2011/0229569 A1, cited herein as “Pilgaonkar ‘569; of record), in view of Navon (US 2011/0117192 A1; of record).
Pilgaonkar ‘569 is drawn to a tablet composition exhibiting delayed transit through the gastrointestinal tract comprising one or more active agents and at least one pharmaceutically acceptable excipient (Abstract; pg 6, [0061]). Pilgaonkar ‘569 teaches levodopa as a suitable active agent (pg 4, [0044] and pg 10, claim 11, lines 1 and 4).
For the limitation of “the swelling agent is polyethylene oxide,” Pilgaonkar ‘569 teaches hydrophilic polymers having swelling and or mucoadhesive properties suitable for incorporation in the compositions of present invention include polyethylene oxide (pg 5, [0055]). Pilgaonkar ‘569 teaches Example 8 (pgs 9-10) comparing a gastroretentive layer comprising polyethylene oxide (Example 8A) with a gastroretentive layer comprising fenugreek fiber (Example 8B) and determines that “the gastroretentive formulation with Polyox® WSR 303 (Example 8A) and fenugreek fiber (Example 8B) exhibited comparable swelling and floating characteristics” (pg 9, [0110]). While Pilgaonkar ‘569 teaches that polyethylene oxide is expensive, hygroscopic, and may undergo oxidation, Pilgaonkar ‘569 further teaches: “Poly (ethylene oxide) is thus the major excipient employed in swelling type of gastroretentive formulations due to its excellent swelling properties.” See (pg 2, [0012]).
Pilgaonkar ‘569 teaches a suitable swelling retardant is ethyl cellulose (pg 5, [0055]).
Pilgaonkar ‘569 teaches a compressed bi-layered gastroretentive tablet (pg 35, claim 15).
Pilgaonkar ‘569 does not teach the or a combination of carbidopa and levodopa.
Navon teaches the missing element of Pilgaonkar ‘569.
Navon teaches multi-layered gastroretentive drug formulations for the controlled release of a combination of levodopa and carbidopa in the upper gastrointestinal tract (pg 1, [0002]; pg 3, [0022]).
Navon teaches an unexpected advantage of adding carbidopa to a gastroretentive comprising levodopa is increasing the plasma half-life of levodopa from about 50 minutes without carbidopa, to about 1.5 hours when carbidopa and levodopa are administered (pg 7, [0088]). Navon teaches (pg 7, [0087]):
The pathogenesis of PD [Parkinson’s Disease] involves degeneration of dopaminergic neurons in the substantia nigra pars compacta and a consequent depletion of the neurotransmitter dopamine in the basal ganglia. Since dopamine cannot cross the blood-brain barrier, Levodopa (LD) (which is enzymatically decarboxylated by the enzyme L-amino dopa decarboxylase in the CNS to dopamine), is used therapeutically to replenish the brain's diminished dopamine reservoir. LD is considered the most effective therapeutic drug for the treatment of Parkinson's disease. Decarboxylation reaction can also occur at some rate peripherally, even before levodopa reaches the brain. Therefore, Levodopa is generally co-administered with an effective L-amino dopa decarboxylase inhibitor such as Carbidopa. The inhibition of Levodopa decarboxylation in the periphery reduces peripheral dopamine formation and decreases the side effects attributed to dopamine (i.e. orthostatic hypotension, nausea and vomiting), while simultaneously increasing the bioavailability of Levodopa to the CNS. Carbidopa/Levodopa is commercially available as a combination products, both as immediate-release (e.g. Sinemet®, Merck & Co., Inc.) or controlled-release ( e.g. Sinemet-CR®, Merck & Co., Inc.) tablets.
For claim 11, Pilgaonkar ‘569 teaches a compressed bi-layered gastroretentive tablet comprising an active layer comprising levodopa, while Navon teaches the advantages of combining levodopa with carbidopa, since carbidopa is an effective L-amino dopa decarboxylase inhibitor (pg 7, [0087]. As stated by Navon ([0088]),
The plasma half-life of LD [levodopa] is about 50 minutes, without Carbidopa (CD). When CD and LD are administered together, the half-life of LD is increased to about 1.5 hours. At steady state, the bioavailability of LD from Sinemet® tablets is approximately 99% relative to the concomitant administration of Carbidopa and LD.
As discussed above, Pilgaonkar ‘569 teaches the claimed active layer as well as the claimed gastro-retentive layer comprising at least one swelling agent and at least one swelling retardant.
For claim 12, Pilgaonkar ‘569 teaches, as discussed above, polyethylene oxide as the swelling agent and the ethyl cellulose as the swelling retardant (see
For claims 13 and 14, Navon teaches a dosage form wherein carbidopa and levodopa are present in total amounts of 75 mg and 300 mg, respectively (pg 8, Example 6). These amounts are considered to read on the limitations of “about 50 mg carbidopa” and “about 200 mg levodopa” since the instant specification fails to define or limit the term “about”.
The skilled artisan would have a reasonable expectation of success in adding carbidopa to the gastroretentive composition comprising levodopa taught by Pilgaonkar ‘569 because Navon teaches that the addition of carbidopa to a gastroretentive composition comprising levodopa increases the plasma half-life of the levodopa from 50 minutes to 90 minutes. The skilled artisan would have been motivated to select Navon's combination of levodopa and carbidopa since Navon teaches the combination of carbidopa with levodopa in the treatment of Parkinson’s disease is a commercial product, and the combination is preferred over levodopa alone since carbidopa inhibits the in vivo decarboxylation of levodopa reducing peripheral dopamine formation and decreasing the side effects attributed to dopamine (i.e. orthostatic hypotension, nausea and vomiting), while simultaneously increasing the bioavailability of levodopa to the CNS.
Examiner’s Reply to Attorney Arguments dated 4/29/2026
1. Rejection of claims 1, 6, and 11-14 under 35 U.S.C. 103 over Pilgaonkar ‘569 and Navon.
The applicant argues that Pilgaonkar ‘569 teaches away from the use of polyethylene oxide as presently claimed in favor of fenugreek fibers.
The Examiner acknowledges the argument presented, but is unpersuaded. In an obviousness determination, a reference may be relied on for all that it would have reasonable suggested to one having ordinary skill in the art. See MPEP 2123(I). In the instant case, as discussed above, Pilgaonkar ‘569 teaches hydrophilic polymers having swelling and or mucoadhesive properties suitable for incorporation in the compositions of present invention include polyethylene oxide. Pilgaonkar ‘569 teaches Example 8 (pgs 9-10) comparing a gastroretentive layer comprising polyethylene oxide (Example 8A) with a gastroretentive layer comprising fenugreek fiber (Example 8B) and determines that “the gastroretentive formulation with Polyox® WSR 303 (Example 8A) and fenugreek fiber (Example 8B) exhibited comparable swelling and floating characteristics.” While Pilgaonkar ‘569 teaches that polyethylene oxide is expensive, hygroscopic, and may undergo oxidation, Pilgaonkar ‘569 further teaches: “Poly (ethylene oxide) is thus the major excipient employed in swelling type of gastroretentive formulations due to its excellent swelling properties”. As interpreted by the Examiner, the teaching of Pilgaonkar ‘569 is that the potential issues of expense, manufacturing and storage, may been overcome since polyethylene oxide polymer is found in most of the prior research work and numerous patents (see [0010]-[0012]), and , Pilgaonkar ‘569 includes polyethylene oxide as a hydrophilic polymer suitable for incorporation in the claimed dosage form ([0050]). Furthermore, Example 8 of , Pilgaonkar ‘569 teaches polyethylene oxide performs as well as, or is superior to, the fenugreek fiber.
The applicant acknowledges:
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and further argues: “The '569 Publication therefore teaches away from polyethylene oxide, and rather suggests using the less expensive and easier to handle material fenugreek fiber.
As best understood by the Examiner, the applicant supports the Examiner’s position that Pilgaonkar ‘569 teaches polyethylene oxide as an equivalent to fenugreek fiber as an effective swelling agent in gastro-retentive tablets. Regarding the allegation that polyethylene oxide is too expensive and difficult to handle to be useful as a pharmaceutical excipient, the Examiner refers to the teachings of the evidentiary reference of D’souza (“Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications,” Expert Opinion On Drug Delivery, 2016, vol. 13, no. 9, 1257–1275) which discloses the following (pg 1257, “Introduction”:
Polyethylene glycol (PEG) is a polymer of choice in drug delivery systems. This USFDA-approved polymer is popular due to its tunable properties and well-established safety profile: prime requisites considered during the selection of any excipient in formulation development.
Of note is D’souza’s disclosure that “Polyethylene oxide and PEG both share the same Chemical Abstracts Society (CAS) number” (pg 1257, “1.2. Nomenclature of PEG and derivatives.”
As such, D’souza discloses that polyethylene oxide is a common ingredient in drug delivery systems, and is safe to use in a drug formulation.
CONCLUSION
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 MICHAEL P COHEN whose telephone number is (571)270-7402. The examiner can normally be reached on M-Th 8:30-5:30; F 9-4.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup, can be reached on (571)272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHAEL P COHEN/Primary Examiner, Art Unit 1612
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