DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-13, in the reply filed on 11/25/2025 is acknowledged. The traversal is on the ground(s) that “Group II claims are drawn to a process that requires all the limitations of a product of Group I”. This is not found persuasive because the product of Group I can be used in a materially different process of using that product since prolactin secretion and growth hormone are regulated by dopamine.
The requirement is still deemed proper and is therefore made FINAL.
Claims 14-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-8, 10-13 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Segral (US 2008/0255235) in view of Tsukada et al., (US 4,409,233) and further in view of Klement et al., (British Journal of Anasthesia 1991).
Segral teaches, “An infusion or injection solution of Levodopa containing at least 10 mg/mL of Levodopa, or at least 5 mg/mL of Levodopa together with at least 0.5 mg/mL of at least one inhibitor of a Levodopa-metabolizing enzyme” (Abstract)
The Levodopa-metabilizing enzyme may be one of the “dopa decarboxylase (DDC) inhibitors” such as “carbidopa” and “entacapone” (p. 2, para. [0026]-[0028]).
The reference teaches a specific embodiment of a Levodopa solution comprising water and Carbidopa:
PNG
media_image1.png
168
515
media_image1.png
Greyscale
(p. 3, para. [0040]). Note: sodium pyrosulfite qualifies as excipient, as per claim 8.
Since the amount of the at least one inhibitor of a Levodopa-metabolizing enzyme is at least 0.5 mg/mL it would have been obvious to have at least about 2% or 4% carbidopa, as per claims 2-3. "[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" (see MPEP 2144.05 IIA quoting In re Aller, 220 F.2d 454, 456 (105 USPQ 233)).
The compositions of Segral are reasonably expected to be stable at 25ºC for 48 hours or more, as per claim 4, insofar as Segral teaches, “A solution of 5 mg/mL Levodpa and 0.5 mg Carbidopa has been heated to 60ºC. and left to stand for 36 hours, and then at room temperature for 1 week, without any sign of discoloration or precipitation (p. 4, para. [0046]).
Since the compositions are taught to be stored at “room temperature” (Id.), it would have been obvious for the compositions to have a temperature of 25ºC, as per claims 1 and 4.
Segral does not teach arginine or wherein the pH of the liquid is about 7 to about 9 at 25ºC.
Tsukada et al. teaches an “aqueous composition of a dopa which comprises dopa and at least one amino acid selected from the group consisting of . . . arginine . . .” (Abstract), based on the discover “that a dopa can be dissolved in a high concentration (10-100 mg/ml) by adding a basic amino acid and/or a certain type of neutral amino acid to the dopa compound” (col. 1, lines 45-49).
The reference teaches a specific embodiment comprising 2.0g arginine and 2.0g dopa (col. 2, Example 1, lines 30-36).
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s invention to combining the arginine of Tsukada et al. with the levodopa carbidopa solution of Segral for the advantage of solubilizing dopa, as taught by Tsukada et al.
The combination would have provided the arginine salt of cabidopa, as per claims 12-13.
The artisan would have modified the molar ratio of the combination arginine and dopa, as per claims 5-6, as a means for adjusting the dosage of active dopa and the solubilizing effect of the arginine. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.");
The combination of Segral and Tsukada et al. does not teach a pH of about 7 to about 9.
Klement et al. “studied the intensity and time-course of pain during and after injection into an isolated vein segment in several normal subjects” (see Summary, at p. 89) based on the osmolality or pH of the injection formulations. The study found, “Acidic and alkaline solutions evoked pain at a pH value < 4 or > 11” (Id.). They concluded, “Pain on injection and perhaps also thrombophlebitis can probably be avoided by diluting hyperosmolar drug formulations with distilled water or by aspirating blood for buffering into formulations with extreme pH just before injection” (p. 194, right col. last para.).
Accordingly, it would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to provide a pH for injection falling withing the range of 4 to about 11, e.g. the claimed pH range of about 7 to about 9, as taught by Klement et al., to provide a pH in a physiologically acceptable range that avoids pain in the subject.
2) Claim 9 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Segral (US 2008/0255235) in view of Tsukada et al., (US 4,409,233) and further in view of Klement et al., (British Journal of Anasthesia 1991) as applied to claims 1-8, 10-13 above, and further in view of Strickley (Pharmaceutical Research, 2004).
The combination of Segral, Tsukada et al., and Klement et al., differs from claim 9 insofar as it does not teach the excipients recited therein.
Strickley teaches solubilizing excipients for oral and injectable formulations (Ti).
“A review of commercially available oral and injectable solution formulations reveals that the excipients include water-soluble organic solvents (polyethylene glycol 300, polyethylene glycol 400, ethanol, propylene glycol, glycerin, N-methyl-2-pyrrolidone, dimethylacetamide, and dimethylsulfoxide) . . . (Abstract; see also p. 214, right column, 1st full paragraph).
“The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945)” (see MPEP 2144.07).
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to select propylene glycol or N-methyl-pyrrolidone as excipient in the injectable formulations of Segrell, based on their art recognized suitability for their intended use in injectable formulations, as taught by Strickley.
Nonstatutory Obvious-type Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
1) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 9,993,451. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient.
2) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 7,863,336. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient.
3) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 8,193,243. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient.
4) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 9,040,577. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient. The inclusion of Levodopa would have been obvious, since carbidopa functions to prevent Levodopa metabolism in vivo before it gets through the blood brain barrier.
5) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 9,040,578. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient. The inclusion of Levodopa would have been obvious, since carbidopa functions to prevent Levodopa metabolism in vivo before it gets through the blood brain barrier.
6) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9,040,589. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient. The inclusion of Levodopa would have been obvious, since carbidopa functions to prevent Levodopa metabolism in vivo before it gets through the blood brain barrier.
7) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,040,590. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient. The inclusion of Levodopa would have been obvious, since carbidopa functions to prevent Levodopa metabolism in vivo before it gets through the blood brain barrier.
8) Claims 1-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 9,421,267. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim compositions comprising carbidopa and arginine. Adjustment of the formula pH would have been obvious as a means for providing a pH that is physiologically tolerable for the patient. The inclusion of Levodopa would have been obvious, since carbidopa functions to prevent Levodopa metabolism in vivo before it gets through the blood brain barrier.
Conclusion
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER E WEBB whose telephone number is (571)270-3287 and fax number is (571) 270-4287. The examiner can normally be reached from Mon-Fri 7-3:30.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Walter E. Webb
/WALTER E WEBB/Primary Examiner, Art Unit 1612