DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
Claims 1-27 are pending and under current examination in this application. Amendment to the claims and Specification filed 15 February 2024, are acknowledged. Claims 4, 5, 7-12, 14-23, and 25 have been amended and are supported by the originally-filed disclosure.
Claim Objections
Claim 23 is objected to because of the following informalities:
Claim 23 is objected to because it recites the use of “carbodopa” which is misspelled and should be corrected to “carbidopa”.
Claim Rejections - 35 USC § 112(b)
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 Applicant regards as his invention.
Claim 11 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, regards as the invention.
Claim 11 reads, “The method of claim 1, wherein the composition is in the form of a granule, a pellet, a powder, a tablet, a minitablet, a suspension, a paste, a non-aqueous liquid, an oil, a polyethylene glycol, a gastroretentive device and combinations thereof.” The claim uses the conjunctive term “and” in a list that concludes with the phrase “combinations thereof.” This structure creates ambiguity as to the scope of the claim and fails to inform one of ordinary skill in the art about the metes and bounds of the invention with reasonable certainty, as required by Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898 (2014).
Specifically, the recitation “a granule, a pellet, a powder… a gastroretentive device and combinations thereof” is unclear because it is impossible to determine whether the composition must be in a form that encompasses all of the listed forms simultaneously (i.e., a single composition that is a granule, a pellet, a powder, etc., at the same time), which would render the claim inoperative, or the composition may be in any one of the listed forms (i.e., in the alternative), which is the more likely intended meaning but is contradicted by the use of the conjunctive “and”. The composition may be in a combination of two or more of the listed forms, as suggested by “combinations thereof,” but the relationship of this option to the preceding list joined by “and” is grammatically and logically ambiguous. The use of “and” to connect the final item, “a gastroretentive device”, immediately before “combinations thereof,” compounds the ambiguity as to whether “combinations thereof” is linked only to “a gastroretentive device” or to the entire preceding list. This lack of clarity leaves the scope of the claim uncertain (see MPEP § 2173.05(e)).
To overcome this rejection, applicant may amend the claim to clarify the intended meaning (e.g., “…wherein the composition is in a form selected from the group consisting of a granule, a pellet, a powder, a tablet, a minitablet, a suspension, a paste, a non-aqueous liquid, an oil, a polyethylene glycol, a gastroretentive device, and combinations thereof.”, “…wherein the composition is in the form of at least one of a granule, a pellet, a powder…, and a gastroretentive device, or a combination thereof.”, or “…wherein the composition is in the form of a granule, a pellet, a powder…, a gastroretentive device, or a combination of any of the foregoing.”).
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 (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.
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 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 1-27 are rejected under 35 U.S.C. § 103 as being unpatentable over Han et al. (US20060013875A1; published 19 January 2006, hereinafter referred to as “Han”) in view of Navon et al. (WO2012059815A1; published 10 May 2012, hereinafter referred to as Navon) and in further view of Menachem and Zalit (WO2015187746A1; published 10 December 2015, hereinafter referred to as “Menachem”).
Han teaches oral administration (see claim 2) dosage forms of carbidopa and levodopa with immediate and controlled release components for treating ailments like Parkinson's disease (¶[0002] and ¶[0004]). Han teaches delivering within hard or soft gelatin capsules an effective amount of pharmaceutical drug combination (i.e., levodopa and carbidopa) in the composition by mixing [dispersing] with the relevant ingredients and granulating the mixture (¶[0075]), wherein the capsule may contain a coating [outer shell] and the drug combination particle mixture (i.e., levodopa and carbidopa) contained within the capsule's outer shell (¶[0076]; see also Example 4, ¶[0125]). Inherently, for any properly manufactured pharmaceutical capsule formulation, it is necessary that the pharmaceutical drugs must be uniformly distributed/dispersed through the blended composition before encapsulation to ensure dose accuracy and content uniformity. Han’s claim 12 teaches the use of between about 25-75 mg carbidopa and about 300 mg levodopa, meeting the limitation of instant claim 7. Claim 32 teaches the use of at least about 200 mg levodopa and wherein the ratio of carbidopa to levodopa in the pharmaceutical dosage is from about 1:10.
The instant claim 24 dose of at least 400 mg levodopa and at least 40 mg of carbidopa in encompassed within range taught by Han in claim 32. Han also teaches wherein adjustment of the specific dose level is a matter of routine optimization as, “The skilled artisan will appreciate that daily dosages having an amount of active agent sufficient to treat Parkinson's disease will generally contain from about 25 mg to about 4,000 mg of levodopa in combination with from about 5 mg to about 600 mg of carbidopa…It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including body weight, general health, gender, diet, time and route of administration, rates of absorption and excretion, combination with other drugs, and the severity of the particular disease being treated.” (¶[0049]) and “Taken together, the results of these studies support that optimum doses of carbidopa (or other AAAD inhibitors) vary significantly among individuals who are treated with levodopa.” (¶[0053]), providing a clear motivation to adjust the range. The instant claim 24 dose of at least 400 mg levodopa and at least 40 mg of carbidopa is encompassed within this range.
Choosing the specific dose of instant claim 24 would be a matter of routine experimental optimization, particularly given that evidentiary reference MedCentral Oral Carbidopa-Levodopa Monograph (https://www.medcentral.com/drugs/monograph/3394-382394/carbidopa-levodopa-oral; revised 18 October 2021, accessed 19 December 2025) teaches dosages of immediate-release combination preparation containing 10 mg of carbidopa and 100 mg of levodopa therapy, usually is initiated with 1 tablet 3 or 4 times daily in which this dosage will not provide an adequate amount of carbidopa for many patients and dosage may be increased by 1 tablet every 1 or 2 days until a maximum dosage of 8 tablets daily (80 mg of carbidopa and 800 mg of levodopa), squarely encompassing the instant claim 24 dose range (page 8, paragraph 4).
Han teaches that availability of carbidopa and levodopa combination product immediate release as well as controlled release formulations in the art, wherein the controlled release formulations allow for the continuous release of drug over a prolonged period and dosages taken in the day or evening (¶[0010]). Hence the administration limitations of instant claims 21-23 are taught to be previously known in the art as standard dosing administration protocols by Han.
Han teaches that the administration of a pharmaceutical dosage form of the present invention would provide therapeutic benefit to a human patient (¶[0033]). The evidentiary reference MedCentral Oral Carbidopa-Levodopa Monograph teaches that levodopa is known in the art to be useful in the management akinesia, rigidity, and tremor (extrapyramidal motor) symptoms of parkinsonian syndrome, producing alertness, increased vigor, and a sense of well-being (i.e., treating non-motor Parkinson's disease symptoms such as depression, apathy and cognitive issues), and is useful in a patient with dysphagia and does not exclude the use for other symptoms in patients that are not determined to be dysphagic. Patients treated with levodopa have improved functional ability and other secondary motor manifestations such as those affecting swallowing (page 2, paragraph 3), which would include improving the swallowability of an antiparkinsonian medication. The evidentiary reference also teaches that patients are known to have difficulty swallowing commercially available extended-release carbidopa-levodopa capsule size dosage forms by providing guidance for administering capsule medication in patients with difficulty swallowing by opening the capsules and sprinkle the entire contents on a small amount of applesauce (page 6, paragraph 2).
Crexont® (brand name, formerly IPX203) capsules are commercially available extended-release carbidopa-levodopa capsules having a specific size ranging from standard capsule size 2-00 (approximately 18-23.3 mm length and 6.35-8.53 mm; see evidentiary reference Hauser et al. How to dose extended-release carbidopa-levodopa capsules (IPX203, Crexont®) in patients with Parkinson's disease. Clin Park Relat Disord. 2025 Jun 18;13:100357, page 1, right column, paragraph 1), which are smaller than the instant claimed capsule size of 29-32 mm length and at least about 9.5-10.5 mm width, thus teaching that it is known in the art wherein a patient may have previously been determined to have difficulty swallowing dosage forms smaller than the instant claimed capsule, as in the limitation of instant claim 27.
The instant claimed patient population is "diagnosed with a Hoehn and Yahr rating of at least 2", is not explicitly recited in the teachings of Han. However, by disclosing the treatments taught by Han are for Parkinson's disease, wherein the Hoehn and Yahr scale is a standard clinical staging tool for Parkinson's disease, it thus would have been obvious to one of ordinary skill in the art to administer a known, effective Parkinson's disease medication to patients at a specified, conventional disease stage (Hoehn and Yahr ≥2) as part of routine clinical practice and patient management. This limitation does not impart patentable weight.
Han does not explicitly mention capsules with the precise dimensional limitations of a length of about 29-32 mm and width of about 9.5-10.5 mm, as per the limitations of instant claims 1, 24, 26 and 8 and 9.
Navon teaches a gastroretentive accordion pill for the controlled release of carbidopa/levodopa in an improved method of treatment of Parkinson's Disease symptoms to provides significantly more continuous and stable levodopa plasma levels over a 24-hour period (Abstract), without explicitly stating the capsule size dimensions used in the embodiment of the invention. However, Menachem discloses a gastroretentive dosage form for extended retention in a stomach (Abstract) including an active pharmaceutical ingredient ranging from about 0.1 mg to 2 grams (claim 37), wherein the formulation is positioned in a capsule (claim 84; 106) which may have a length between 26-32 mm and a diameter of less than about 11mm or in other embodiments less than 10mm (¶[000201]), encompassing the instant claimed range dimensions of about 29-32 mm length and 9.5-10.5 mm width.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to adjust the dose range to that of the instant claims in the invention of Han, as dose range adjustments would be motivated by the teaching of such by Han and the specific instant claimed doses would be a matter of routine optimization, as evidence by the evidentiary reference MedCentral Oral Carbidopa-Levodopa Monograph in patients experiencing the instant claimed symptoms or for the treatment of the symptoms, which are also described in the evidentiary reference to be known in Parkinson's Disease patients, wherein levodopa is also known for the treatment of such symptoms. It would have also been obvious to one of skill in the art to administer a known Parkinson's disease medication to patients at a specified, conventional disease stage (Hoehn and Yahr ≥2) as part of routine clinical practice and patient management.
One with skill in the art seeking to reduce the pill burden, pill swallowing difficulty and improve the low bioavailability and short half-life of levodopa, with knowledge of the prior art disclosed in the instant specification ¶[0007], finding that larger hard-shell capsules were more favorable for swallowing ease in Parkinson's disease patient (Buhmann 2019) in combination with the teachings of Navon of an improved method of treatment of Parkinson's Disease using a gastroretentive accordion pill for the controlled release of carbidopa/levodopa in and the specific size of gastroretentive dosage form size dimension ranges for extended retention in a stomach taught by Menachem to arrive at the instant claimed dimensions of about 29-32 mm length and 9.5-10.5 mm width.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA L. SCOTLAND whose telephone number is (571) 272-2979. The examiner can normally be reached M-F 9:00 am to 5:00 pm EST.
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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615