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 .
Claims 1-12, are currently pending in this Application.
Information Disclosure Statement
Applicant’s Information Disclosure Statements, filed on 11/02/2023; 05/07/2024 and 01/27/2025 have been considered. Please refer to Applicant’s copies of the 1449 submitted herewith.
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 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 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 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 1-12 are rejected under 35 U.S.C. 103(a) as being unpatentable over AKIMO, “Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis,” Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, Vol. 18, pp. 55-63, 2017) in view of Toby A. Ferguson et al: “Clinical presentation and diagnosis of amyotrophic lateral sclerosis,” NeuroRehabilitation 22.6 (2007): 409-416.
The instant claims 1-12 are directed to methods of treating ALS ( see claim 1) or suppressing the progress of ALS (see claim 7) using Edaravone, 3-methyl-1-phenyl-2-pyrazolin-5-one,
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. The instant claims also recite some limitation on the patient population, wherein the potential patient population that can be treated exhibit a diagnosis that meets all of the seven pairs codes, wherein the seven pairs of codes are:
a pair of CPT code 82550 (CK or CPK lab test) and ICD-9 code 728.87 (muscle weakness);
a pair of ICD-9 code 728.87 (muscle weakness) and ICD-9 code 780.79 (malaise and fatigue),
a pair of CPT code 82607 (Vitamin B12 test) and ICD-9 code 728.87 (muscle weakness);
a pair of CPT code 82550 (CK or CPK lab test) and CPT code 86038 (a heterophile antibody screening test);
a pair of CPT code 82550 (CK or CPK lab test) and CPT code 82607 (Vitamin B12 test);
a pair of ICD-9 code 787.20 (dysphagia, unspecified) and CPT code 74230 (radiological examination of swallowing function);
and a pair of ICD-9 code 780.79 (malaise and fatigue) and CPT code 82550 (CK or CPK lab test).
Claims 2, 3, 5, 6, 8, 9, and 11-12 limit the method of admiration.
Determination of the scope and contents of the prior art
AKIMO teach edaravone,
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for treating patients who meets all of the following criteria (scores 2 points on all 12 items of the revised ALS functional rating scale (ALSFRS-R), forced vital capacity 80 % definite or probable ALS, and disease duration 2 years. (see Abstract; and Section “Patients” on page 56). The ALSFRS-R measures 12 aspects of physical function, ranging from one's ability to swallow and use utensils to climbing stairs and breathing. Each function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0.
AKIMO also teach method of administration. AKIMO teaches administering edaravone for 14 consecutive days followed by a 14-day drug-free period in Cycle1, and administering for 10 days within a 14-day period followed by a 14-day drug free period in Cycle 2 and thereafter ( see, Section “Study design” on page 56, right column).
AKIMO does not teach wherein the patient is identified by a diagnosis which meets all Pairs 1-7.Toby A. Ferguson et al which relates to ALS and thus is in the same technical field as present application teaches a method of diagnosing ALS through clinical symptoms such as muscle weakness and dysphagia, and clinical examinations, such as creatine kinase examination, vitamin B12 examination, and antinuclear antibody examination (see the full article, including abstract; Tables 2-3)
Resolving the Level of Ordinary Skill in the Pertinent Art
“Factors that may be considered in determining level of ordinary skill in the art include: (1) the educational level of the inventor; (2) type of problems encountered in the art; (3) prior art solutions to those problems; (4) rapidity with which innovations are made; (5) sophistication of the technology; and (6) the education level of active workers in the field.” Envtl. Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983) (citing Orthopedic Equip. Co. v. All Orthopedic Appliances, Inc., 707 F.3d 1376, 1381-82 (Fed. Cir. 1983)). The above factors are not exhaustive, but are a guide. Id.
In this case, the education level of the inventor and the education level of active workers in the field of organic chemistry, as well as the high degree of sophistication required to solve problems encountered in the art, a person of ordinary skill in the art would likely have at least a college degree in the field of organic chemistry, with industry experience, i.e., a masters or doctorate level of skill and knowledge in the laboratory. Thus, the level of skill in the art is relatively high.
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143. Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" — choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel. Here one or more of rationales (C) and (G) apply.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of AKIMO and Toby A. Ferguson et al to use edaravone to treat a patient population characterized by the ALS diagnostic criteria taught by Toby A. Ferguson et al. In the absence of unexpected results, one skilled in the art would use edaravone to treat the patient population described in the instant claims The methods are using identical products to treat ALS. The patient population can be limited by performing the laboratory and other diagnostic tests taught by Toby A. Ferguson et al. As such a person of ordinary skill in the art would have had a reasonable expectation of success in using the method described in the instant claims.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). 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 was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Accordingly, claims 1-12 are rendered obvious in view of the references above. Applicant might consider providing evidence of unexpected results to overcome the rejection.
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 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.
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.
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) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, 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 negatived 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(a) 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.
Claims 1-12 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Patent No. 6,933,310 in view of Bali et al Missouri Medicine | September/October 2013| 110:5 | 417
The instant claims are directed to methods of treating ALS using Edaravone, 3-methyl-1-phenyl-2-pyrazolin-5-one,
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. The instant claims also recite some limitation on the patient population and subpopulation that can be treated based on some test. Some of the tests to limitations include increased CK levels; increase in more diagnostic and laboratory examinations such as muscles weakness test, B12, TSH, CK, swallowing test ” etc.
Determining the Scope and Contents of the Prior Art
U.S. Patent No. 6,933,310 teach are directed to methods of treating ALS using products of the same Formula, 3-methyl-1-phenyl-2-pyrazolin-5-one,
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. U.S. Patent No. 6,933,310 do not limit the patent population that are treated with the aforementioned products. Bali et al teaches management of ALS and also teaches tests that are done to patients suspected to have ALS. These tests include: muscles weakness test, B12, TSH, CK, swallowing test
Ascertaining the Difference Between the Prior Art and Claims
The above reference teaches the same process as disclosed in the instant invention using a solvent mixture containing a ketone, water and acetic acid. In regards to claim 19 the prior art is silent to the particular crystalline form.
Resolving the Level of Ordinary Skill in the Pertinent Art
“Factors that may be considered in determining level of ordinary skill in the art include: (1) the educational level of the inventor; (2) type of problems encountered in the art; (3) prior art solutions to those problems; (4) rapidity with which innovations are made; (5) sophistication of the technology; and (6) the education level of active workers in the field.” Envtl. Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983) (citing Orthopedic Equip. Co. v. All Orthopedic Appliances, Inc., 707 F.3d 1376, 1381-82 (Fed. Cir. 1983)). The above factors are not exhaustive, but are a guide. Id.
In this case, the education level of the inventor and the education level of active workers in the field of organic chemistry, as well as the high degree of sophistication required to solve problems encountered in the art, a person of ordinary skill in the art would likely have at least a college degree in the field of organic chemistry, with industry experience, i.e., a masters or doctorate level of skill and knowledge in the laboratory. Thus, the level of skill in the art is relatively high.
Objective Evidence in the Application Indicating Obviousness or Nonobviousness
The Supreme Court in KSK International Co. v. Teleflex lnc.^ 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSK noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” — choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel. Here one or more of rationales (D) and (G) apply.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to use teachings of U.S. Patent No. 6,933,310 in view of Bali et al to create the instantly claimed invention. The methods are using identical products to treat ALS. The patent population can be limited by performing the laboratory and other diagnostic tests or observations as suggested and taught by Bali et al. As such a person of ordinary skill in the art would have had a reasonable expectation of success in using the method described in Kinoshita et al.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). 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 was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Accordingly, claims 1-12 are rendered obvious in view of the reference above. Applicant might consider providing evidence of unexpected results to overcome the rejection.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAMAL A SAEED, Ph.D. whose telephone number is (571) 272-0705.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Joseph K. McKane, can be reached at (571) 272-0699.
Communication via Internet e-mail regarding this application, other than those under 35 U.S.C. 132 or which otherwise requires a signature, may be used by applicant and should be addressed to [Symbol font/0x5B]joseph.mckane@uspto.gov[Symbol font/0x5D]. All Internet e-mail communications will be made of record in the application file. PTO employees will not communicate with applicant via Internet e-mail where sensitive data will be exchanged or where there exists a possibility that sensitive data could be identified unless there is of record an express waiver of the confidentiality requirements under 35 U.S.C. 122 by the applicant. See the Interim Internet Usage Policy published by the Patent and Trademark Office Official Gazette on February 25, 1997 at 1195 OG 89.
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 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.
/Kamal A Saeed/
Primary Examiner, Art Unit 1626