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 .
Non-Final Rejection
The Status of Claims:
Claims 1-2 and 4-9 are pending.
Claims 1-2, 4 and 6-8 are rejected.
Claims 5 and 9 are objected.
DETAILED ACTION
1. Claims 1-2 and 4-9 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/CA2022/051708 11/21/2022 , which has a priority of 63282297 11/23/2021
Drawings
3. The drawings filed on 5/22/24 were accepted by the examiner .
IDS
4. The IDS filed on 5/29/24 were reviewed by the examiner.
Claim Objections
Claims 5 and 9 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
Claims 1 and 6 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In claim 1, the phrases” a pharmaceutically acceptable ester of D- Cycloserine, or an alkylated D-Cycloserine, or a pharmaceutically acceptable precursor of D-Cycloserine “ are recited . These expressions are vague and indefinite because the claim does not elaborate what is meant by each of the ester of D- Cycloserine” ,”an alkylated D-Cycloserine” ,and “precursor of D-Cycloserine” in terms of their corresponding chemical structures in the claim. An appropriate correction is required.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1 and 6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The issue concerning the meaning of phrase “ a pharmaceutically acceptable precursor of D-Cycloserine ” is to be discussed. Claims 1 and 6 do not contain a complete generic formula.
According to the MPEP §2163 I. A. “the issue of a lack of adequate written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant had possession of the claimed invention. The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.” The MPEP states in §2163 II 3 ii) “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.” Applicants have disclosed no species and have made no assertion that there is any correlation between the function of “a precursor” and the structure of “D-Cycloserine”.
The Court of Appeals for the Federal Circuit held in University of California v. Eli Lilly and Co. 43 USPQ2d 1398 at 1406. "[a] written description of an invention involving a chemical genus, like a description of a chemical species, "requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials." In re Smythe, 480 F.2d 1376, 1383, Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . .")." Applicants' functional definitions in the claimed formula simply lack the precision required by the Court of Appeals for the Federal Circuit.
As discussed above the phrase “ a pharmaceutically acceptable precursor of D-Cycloserine ” is not art recognized in the art of chemistry in the absence of a definitive chemical structure of the “precursor”. According to the MPEP §2163.02 Standard for Determining Compliance With the Written Description Requirement,
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed". In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter". Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
Thus, the chemist of ordinary skill in the art, who would use Applicants' compounds, would not know what “ a pharmaceutically acceptable precursor can be suitable for D-Cycloserine. That chemist would not have understood the inventor to be in possession of the claimed pharmaceutically acceptable precursor of D-Cycloserine at the time of filing.
This case was filed before Applicants had a clear idea of the structures of their desired compounds, how to make their compounds, and use the precursor of D-Cycloserine made from them. The specification provides broad areas of future research and speculation, inviting undue experimentation in learning how to use Applicants' invention. Applicants may well now be developing practical applications of their precursor of D-Cycloserine , but the question here is what application they possessed at the time of filing. Anything is possible but as the U.S. Patent and Trademark Office, Board of Patent Appeals and Interferences wrote in Bindra v. Kelly, 206 USPQ 570 “Probable utility does not establish practical utility. Practical utility can, in our view, be established only by actual testing therefore, or by establishing such facts as would be convincing that such utility could be "foretold with certainty.” Blicke v. Treves, supra, 112 USPQ at 475.”
Applicants are reminded of what the U.S. Court of Appeals Federal Circuit wrote in University of California v. Eli Lilly and Co. 43 USPQ2d 1398, "In claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus." "A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). "It is only a definition of a useful result rather than a definition of what achieves that result." "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.")".
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, 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.
5. Claims 1-2, 4, and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Pradhan (WO 2016/061320 A2).
Applicants claim the followings:
1. (ORIGINAL) A method of treating Obsessive Compulsive Disorder (OCD) comprising administering adjunctive D-Cycloserine or a pharmaceutically acceptable ester of D- Cycloserine, or an alkylated D-Cycloserine, or a pharmaceutically acceptable precursor of D-Cycloserine to augment transcranial magnetic stimulation (TMS) therapy for OCD, optionally intermittent or continuous theta-burst stimulation, high- or low-frequency stimulation, and combinations thereof, to improve and/or alleviate and/or reduce frequency of one or more symptoms of OCD.
2. (ORIGINAL) A method of treating OCD in a patient and/or improving and/or alleviating and/or reducing the frequency of one or more symptom of OCD, the method comprising:administering to the patient a low dose of D-Cycloserine, optionally 1-250mg per patient; and subjecting the patient to transcranial magnetic stimulation, optionally intermittent or continuous theta-burst stimulation, high- or low-frequency stimulation, and combinations thereof.
4. (ORIGINAL) The method of claim 2, wherein the low dose is a dose of D-cycloserine
6. (CURRENTLY AMENDED) The method of claim 1,wherein D-Cycloserineis administrated at a dose formulated to achieve maximal plasma levels of 1-30 pg/mL within six hours for to support adjunctive use in the treatment of OCD using of the transcranial magnetic stimulation, optionally intermittent or continuous theta-burst stimulation, high- or low-frequency stimulation, and combinations thereof.
7. (ORIGINAL) A method of improving and/or reversing and /or partially reversing cognitive impairment in OCD, including executive function and cognitive control, the method comprising: administering to the patient a low dose of D-Cycloserine and subjecting the patient to transcranial magnetic stimulation, optionally intermittent or continuous theta- burst stimulation, high- or low-frequency stimulation, and combinations thereof.
8. (NEW) The method of claim 7, wherein the low dose is a dose of D-cycloserine sufficient
Determination of the scope and content of the prior art
Pradhan discloses a method of improving or treating an anxiety disorder such as substance-abuse disorders, mood disorders, panic disorder, agoraphobia, social phobia, specific phobia, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder, and movement disorders by administering a therapeutically effective amt. of a therapeutic agent such as D-Cycloserine. ; furthermore, the method further includes exposing the patient to transcranial magnetic stimulation as in claims 1-2, 7 (TMS) (see pages 39-40, claims 1-2, 13, 16).
The therapeutically effective dose of the therapeutic agent can be administered using any medically acceptable mode of administration. Although the skilled artisan would contemplate any of the modes of administration known to one of ordinary skill, preferably the pharmacologic agent is administered according to the recommended mode of administration, for example, the mode of administration listed on the package insert of a commercially available agent(see page 25, lines 9-14).
. In addition, an intranasal or intravenous dose of ketamine for a subject of 80 kg body weight is equal to or greater than about 40 mg, for example, about 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, or 250 mg(see page 27, lines 1-5).
Regarding transcranial magnetic stimulation (TMS) in PTSD, Transcranial magnetic stimulation (TMS) or repetitive TMS (rTMS) may also be used in conjunction with the above described method. The exact time in length of a patient's exposure to TMS or rTMS may vary, depending upon factors such as the identity, size, and condition of the patient treated. One of ordinary skill in the art will be able to determine the intensity and timeframe of the stimulation without undue experiments .
Clinical trials done over the last two decades have demonstrated effectiveness of rTMS in PTSD. It has been demonstrated significant improvements in PTSD symptoms after 24-hour mark. In an open trial involving six patients with treatment resistant -PTSD, significant improvement was observed in hostility, insomnia, anxiety and depression as well as a small but significant improvement in core PTSD symptoms(see page 21, lines 11-22).
The current invention, however, differs from the prior art in that the claimed low dose of D-Cycloserine, optionally l-250mg per patient and achieving a plasma concentration of D-cycloserine of 1-30 µg/mL are unspecified in the prior art.
Ascertainment of the difference between the prior art and the claims
1. The difference between the instant application and the applied Pradhan art is that the Pradhan does not expressly teach the claimed low dose of D-Cycloserine, optionally l-250mg per patient and achieving a plasma concentration of D-cycloserine of 1-30 µg/mL.
Resolving the level of ordinary skill in the pertinent art.
Regarding the claim 2 with respect to the lack of disclosing the claimed low dose of D-Cycloserine, optionally l-250mg per patient, the prior art does teach indirectly that the intranasal or intravenous dose of ketamine which is similar to D-Cycloserine as a therapeutic agent for a subject of 80 kg body weight is equal to or greater than about 40 mg to about 250 mg(see page 27, lines 1-5).
From this information , it seems reasonable for the skilled artisan in the art to be able to estimate approximately the dose of D-Cycloserine per patient. Thus, the prior art is still relevant to the claimed invention.
Regarding the claims 4, 6, 8 with respect to the lack of disclosing the plasma concentration of D-cycloserine of 1-30 µg/mL, the prior art is silent about it .
However, this is a part of a routine evaluation process for the patent who were treated by administering D-cycloserine, but not as a patentable weight over the prior art. Therefore, it is within the purview of the skilled artisan in the art to collect the patient’s plasma concentration of D-cycloserine routinely.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Pradhan expressly discloses the method of improving or treating an anxiety disorder such as obsessive-copulsive disorder, and movement disorders by administering a therapeutically effective amount of a therapeutic agent of D-Cycloserine and subsequently, exposing the patient to transcranial magnetic stimulation(TMS).
Although the prior art does teach the claimed low dose of D-Cycloserine, optionally l-250mg per patient, the prior art does describe indirectly that the intranasal or intravenous dose of ketamine similar to D-Cycloserine as a therapeutic agent for a subject of 80 kg body weight is equal to or greater than about 40 mg to about 250 mg(see page 27, lines 1-5).
From this, it seems reasonable for the skilled artisan in the art to be able to estimate approximately the dose of D-Cycloserine per patient.
So, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to estimate the dose of D-Cycloserine per patient from the dose guidance of ketamine as an alternative therapeutic agent for a patient with obsessive-copulsive disorder.
This is because such a practice is within the purview of the skilled artisan in the art to do so.
Conclusion
Claims 1-2, 4 and 6-8 are rejected.
Claims 5 and 9 are objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 7/11/2026
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