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 .
Response to Election/Restriction
Applicant's election, without traverse, of Group II, claims 25, 27, 30-31 and 36-37, drawn to a method of treating Alzheimer’s disease, in the reply filed on February 28, 2025 is acknowledged. .
Claim 1-4, 21-22, 24 and 44-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 28, 2025.
Claimed Priority
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Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
In the instant case, the disclosure of the provisional application 62/873,566, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Accordingly, claims 25, 27, 30-31 and 36-37, are not entitled to the benefit of the provisional application since particular embodiments of the claims are not supported by the original disclosure of the prior-filed application. Compositions used in the method, such as that of Example 1 and nanoemulsion preparations, were not described in the provisional application. The compositions/preparations encompassed by the claims are particularly those embodiments that are disclosed in the specification of this application. Introduction of examples and nanoemulsion preparations affects the claims. Thus, the provisional application does not support current embodiments that are disclosed in the application and encompassed by the breadth of the claims.
Thus, the effective filing date of claims 25, 27, 30-31 and 36-37 is the filling date of PCT/US20/41719, which is July 10, 2020.
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.
Claims 25, 27, 30-31 and 36-37 are the subject of this Office Action.
Specification Objection – New Matter
The amendment filed July 29, 2022 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
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Applicant is required to cancel the new matter in the reply to this Office Action.
MPEP 211.02(a) states that “When a benefit claim is submitted after the filing of an application, the reference to the prior application cannot include an incorporation by reference statement specifying of the prior application unless an incorporation by reference statement specifying of the prior application was presented upon filing of the application. See Dart Indus. v. Banner, 636 F.2d 684, 207 USPQ 273 (C.A.D.C. 1980). An incorporation by reference statement added after an application’s filing date is not effective because no new matter can be added to an application after its filing date (see 35 U.S.C. 132(a) ).”
Claim Objections
Claims 25, 27, 30-31 and 36-37 are objected to as being dependent of a withdrawn claim. The claims depend of withdrawn claim 1 for the composition. Applicant is required to add the appropriate limitations of the composition to the elected invention of claim 25.
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 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.
Claims 25, 27, 30-31 and 36-37 are rejected under 35 U.S.C. 103 as being unpatentable over Mukunda (WO2019/190608A1) and Cao (Journal of Alzheimer’s Disease 42 (2014) 973-984-cited by applicant in the IDS of 04/06/2022), in view of Craft (Arch Neurol. 2012 January; 69(1): 29-38), Wermeling (US 2007/0060639) and Sood (J. Drug Target, 2014; 22(4); 279-294).
Applicant’s Invention
The present application is drawn to a method of treating Alzheimer’s disease with a composition comprising a combination of tetrahydrocannabinol (THC), melatonin, and insulin, and at least one excipient.
Mukunda
Mukunda teaches a method of treatment of Alzheimer’s disease using a composition comprising a combination of THC (tetrahydrocannabinol), melatonin and curcumin with excipients (see page 10). THC is administered in an ultra-low dose from about 0.2 µg to about 0.14 µg/kg of body weight, preferably from about 0.2 µg to about 0.03 mg/kg of body weight (page 13). Melatonin is administered in dose ranges from about 0.02 mg to about 0.3 mg/kg of body weight, preferably from about 0.01 mg to about 0.15 mg/kg of body weight (p. 13-14). They are combined in an oral suspension to be given once a day, twice a day, thrice a day or four times a day depending on the severity of the symptoms. Oral formulations are made in an ethanol/water mixture and, for example have (see examples).
Mukunda does not teach insulin.
Cao
Cao teaches that THC is effective at lowering Aβ levels at extremely low concentrations by interacting directly with Aβ peptide and inhibiting aggregation, and could be useful in the treatment of Alzheimer’s disease. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin’s enhancement of mitochondria function.
In addition,
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Craft
Craft discloses that in clinical trials, intranasal insulin treatment improves memory in both Alzheimer’s patients and adults with aMCI. Craft teaches that insulin modulates the levels of Aβ and protects against the detrimental effects of Aβ oligomers on synapses. Regarding the benefits of intranasal administration, Craft discloses that it provides rapid delivery of insulin to the central nervous system via bulk flow along olfactory and trigeminal perivascular channels, and slower delivery via olfactory bulb axonal transport, without adversely affecting blood insulin or glucose levels. Intranasal insulin increases insulin levels in cerebrospinal fluid (CSF) and acutely enhances memory in humans. Intranasal insulin was administered at doses of 20 IU (10 IU twice a day) or 40 IU (20 IU twice a day).
Craft does not teach THC or melatonin.
Wermeling
Wermeling teaches compositions for the intranasal administration of THC with the advantages of rapid and controlled absorption and consistent bioavailability. The compositions are to be used in the treatment of conditions associated with CNS disfunction, such as Alzheimer’s disease. See whole document.
Wermeling does not teach melatonin or insulin.
Sood
Sood discusses the benefits of intranasal therapeutic strategies for the management of Alzheimer’s disease. Intranasal delivery provides fast onset of action, avoidance of the intestinal and hepatic presystemic disposition, reduction of systemic exposure and side effects with direct delivery and targeting to the brain and CSF, practicality and ease of administration and better patient compliance. It allows for the administration of lower doses and in return reduce their side effects. (See page 282) Sood teaches that melatonin protects neurons against Aβ toxicity and inhibits the progressive formation of β-sheets and amyloid fibrils; however, it has low oral BA, short biological half-life and erratic pharmacokinetic profile. They have found that intranasal (IN) administration of melatonin enhances drug absorption (see page 290).
Sood additionally teaches that IN insulin improves memory, attention and function in Alzheimer patients (see page 288). Sood does not teach THC.
Further, Sood concluded the following:
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Finding of prima facie obviousness--rational and motivation
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.
Applying KSR exemplary rationale (A), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat Alzheimer’s disease with an intranasal composition of a combination of THC, melatonin and insulin, together with at least one excipient. Each agent was taught in the prior art to be used for treating Alzheimer’s disease. The advantages of their intranasal administration were also disclosed by the references. A person having ordinary skill would have had a reasonable expectation that administering an intranasal combination of the three anti-Alzheimer’s drugs and excipient would effectively treat Alzheimer’s disease in a patient.
It has been held that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). MPEP 2144.06.
With respect to claims 27, 30, 31 and 36, it would have been prima facie obvious to exemplify any of the ultra-low doses from about 0.2 µg to about 0.14 µg/kg of body weight of THC as taught by Mukunda, any of doses of melatonin of from about 0.02 mg to about 0.3 mg/kg of body weight as taught by Mukunda (or references in Sood), and any of the IN insulin doses taught by Craft (20 IU or 40IU per dose) with a reasonable expectation of success. That is because the references teach that these are effective doses for treating AD. Additionally, the dose administered to the AD patient is considered a result-effective variable that impacts the effectiveness of the treatment. See for example the various doses researched/tested in the references. “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In addition, it would have been obvious to administer the composition once a day (24h intervals), twice a day, thrice a day or four times a day depending on the severity of the symptoms, because Mukunda taught so. Also, because the dosing intervals (i.e., 6 hour intervals, etc.) is considered a result-effective variable that impacts the effectiveness of the treatment. Differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 25, 27, 30-31 and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,065,225 in view of Craft (Arch Neurol. 2012 January; 69(1): 29-38), Wermeling (US 2007/0060639) and Sood (J. Drug Target, 2014; 22(4); 279-294).
The claims of the patent do not teach insulin.
Craft
Craft discloses that in clinical trials, intranasal insulin treatment improves memory in both Alzheimer’s patients and adults with aMCI. Craft teaches that insulin modulates the levels of Aβ and protects against the detrimental effects of Aβ oligomers on synapses. Regarding the benefits of intranasal administration, Craft discloses that it provides rapid delivery of insulin to the central nervous system via bulk flow along olfactory and trigeminal perivascular channels, and slower delivery via olfactory bulb axonal transport, without adversely affecting blood insulin or glucose levels. Intranasal insulin increases insulin levels in cerebrospinal fluid (CSF) and acutely enhances memory in humans. Intranasal insulin was administered at doses of 20 IU (10 IU twice a day) or 40 IU (20 IU twice a day).
Wermeling
Wermeling teaches compositions for the intranasal administration of THC with the advantages of rapid and controlled absorption and consistent bioavailability. The compositions are to be used in the treatment of conditions associated with CNS disfunction, such as Alzheimer’s disease. See whole document.
Sood
Sood discusses the benefits of intranasal therapeutic strategies for the management of Alzheimer’s disease. Intranasal delivery provides fast onset of action, avoidance of the intestinal and hepatic presystemic disposition, reduction of systemic exposure and side effects with direct delivery and targeting to the brain and CSF, practicality and ease of administration and better patient compliance. It allows for the administration of lower doses and in return reduce their side effects. (See page 282) Sood teaches that melatonin protects neurons against Aβ toxicity and inhibits the progressive formation of β-sheets and amyloid fibrils; however, it has low oral BA, short biological half-life and erratic pharmacokinetic profile. They have found that intranasal (IN) administration of melatonin enhances drug absorption (see page 290).
Sood additionally teaches that IN insulin improves memory, attention and function in Alzheimer patients (see page 288). Sood does not teach THC.
Further, Sood concluded the following:
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Finding of prima facie obviousness--rational and motivation
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.
Applying KSR exemplary rationale (A), it would have been prima facie obvious to one of ordinary skill in the art to treat Alzheimer’s disease with a composition of a combination of THC and melatonin at the doses recited in the patented claims, in combination with insulin at the dose taught in the references and at least one excipient. Each combination was taught in the prior art to be used for treating Alzheimer’s disease. Further, the advantages of intranasal administration of each ingredient were disclosed by the references. Thus, a person having ordinary skill would have had a reasonable expectation that administering an intranasal combination of THC and melatonin at the doses recited in the patented claims, together with a dose of insulin recited in the references and excipient, would effectively treat Alzheimer’s disease in a patient.
It has been held that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). MPEP 2144.06.
The same doses of THC and melatonin and administration intervals as claimed here are recited in the patented claims.
Conclusion
Claims 25, 27, 30-31 and 36-37 are rejected. No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALERIE RODRIGUEZ-GARCIA whose telephone number is (571)270-5865. The examiner can normally be reached Monday-Friday 9:30am-4:30pm.
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/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1759 04/13/2025