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 .
Detailed Action
Filing Receipt and Priority
The filing receipt mailed 09/15/2022 states the instant application is a continuation of PCT/US2021/012869, filed 01/10/2021 which claims benefit of provisional applications 62/959,534, 62/980,053, and 63/022,484 filed 01/10/2020, 02/21/2020, and 05/09/2020 respectively.
The instant application finds support in the 62/959,534 provisional. Therefore the effective filing date is 01/10/2020.
Information Disclosure Statement
The information disclosure statement submitted on 04/01/2206 has been considered.
Response to Amendments
The amendments made to the claims 04/01/2026 have been entered.
Restriction/Species Election
The election of the following group and species was acknowledged.
Applicant has elected without traverse Group I, claims 35, 37, 41-46, 48, 49, 51, and 55-62.
Applicant elected the following species.
-a compound of formula II shown below,
-a method for treating,
-narcolepsy.
Compound of Formula II
PNG
media_image1.png
144
286
media_image1.png
Greyscale
Applicant stated that the elected species read on claims 35, 37, 44-46, 48, 49, 51, and 60-62.
Claims 41-43, 55, and 57-59 were withdrawn from further consideration as being drawn to non-elected species.
Claim 51 is drawn to methods of claim 35 wherein the subject has Prader-Willi Syndrome.
Claims 60-62 are drawn to methods of claim 35 wherein the subject has hypnagogic hallucinations, hypnopompic hallucinations, or sleep paralysis respectively.
Prader-Willi syndrome is a distinct condition from narcolepsy. Hypnagogic and hypnopompic hallucinations are noted as symptoms of narcolepsy. Likewise, sleep paralysis is also a symptom of narcolepsy. However, the above symptoms are not always present in narcolepsy. Therefore, claims 51 and 60-62 are withdrawn from further prosecution being drawn to unelected species.
At examiner’s discretion, examination has been broaden to include cataplexy claim 56).
Status of claims
Claims under examination are claims 35, 37, 44-46, and 48-49, and 56.
Rejections
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.
Claim(s) 35, 37, 44-46, 48-49 and 56 is/are rejected under 35 U.S.C. 103 as being unpatentable over Naganuma (Neurobiology of Disease 120, 2018, 12-20) in view of Guzzo (US9650378, published 2017), Abad (Nature and Science of Sleep, 2017:9 39-57) and Barateau (CNS Drugs, 2016, 30:369-379).
KSR Rationales
The MPEP in section 2143, subsection I gives examples of Rationales for supporting a conclusion of obvious. These rationales are non-exhaustive and 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.
Independent claim 35 is drawn to a method of treating narcolepsy comprising administering the following compound of formula II or deuterated forms (non-elected species)
Compound of formula II
PNG
media_image1.png
144
286
media_image1.png
Greyscale
Dependent claim 37 is drawn to the compound of formula II (non-deuterated), above.
Dependent claims 44-46 are drawn to effects of administering the compound above. Specifically, claim 44 is drawn to a method of administering wherein the administration achieves a steady state plasma concentration at about 5 to 4000 ng/m, claim 45 is drawn to embodiments wherein the steady state is achieved after 3 to 5 times the elimination half-life or between 7 to 14 days after periodic administration, and claim 46 is drawn to embodiments wherein plasma concentration of claim 44 is the trough level or trough concentration (lowest concentration) is reached before a second administration or is determined from blood samples taken between about 2 hours and 24 hours after the last dose or administration.
Dependent claims 48-49 are drawn to specific narcolepsy types which are narcolepsy type 1 and type 2.
Regarding claim 35 and 56, Naganuma teaches methods of administering an MCH receptor antagonist (SNAP 94847) (abstract). Naganuma on p. 14, sec. 3.2 Experiment 2: blockade of MCH signaling in a mouse model of narcolepsy teaches administration of the MCHR1 antagonist SNAP 94847. Naganuma in sec. 4.4 states “SNAP 94847 dramatically reduced baseline amounts of cataplexy and SLREMS in OC-KO mice. In the 6 h after vehicle, the OX-KO mice displayed moderate amounts of cataplexy and SLREMS, but SNAP 94847 reduced cataplexy by 80% and SLREMs by 75%.” Naganuma on p. 19, sec. 6 states “As the present study was designed to primarily evaluate the role of MCH neurons in narcolepsy, we injected the MCHR1 antagonist, SNAP 94847 only in mouse model of narcolepsy, and our results convincingly show that this drug strongly attenuates narcolepsy symptoms.” Additionally, Naganuma in sec. 7, states “MCH antagonism strongly reduces both cataplexy and abnormal REM sleep transitions. These results suggest a causal role for MCH neurons in narcolepsy.”
Naganuma therefore shows that MCH antagonism is an effective method of treating symptoms of narcolepsy and/or cataplexy. However, Naganuma does not teach the specific compound of formula II. This is addressed by the combination of Guzzo.
Regarding claim 35 and 37, Guzzo in col. 275 teaches compound 49, shown below, which is the hydrochloride salt of the instant compound.
Guzzo, compound 49
PNG
media_image2.png
168
338
media_image2.png
Greyscale
Guzzo in col. 254, l. 31-34 states “By methods as described above, the compounds listed in Table 1 were synthesized and tested for biological activity. All compounds in Table 1 exhibited Kf of less than or equal to 3.5 μM in MCH1 binding assays I and II”. Additionally, Guzzo in col. 1, l. 15-20 states “The invention relates to human melanin-concentrating hormone (MCH1) receptor-selective antagonists.” This statement indicates that the compounds in Guzzo are MCH antagonists.
Regarding claims 44-46 which, as stated above, are drawn to conditions that are a result of administering the compound of Formula II, the claim limitations are essentially properties of the compound. While the art is silent to the specific properties, said properties are inherent to the compound which is disclosed in the art. The MPEP section 2112, subsection I states:
““[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.”
Therefore, the limitations of claims 44-46 do not make the claims patentable as the compound was disclosed in the prior art.
Naganuma and Guzzo do not explicitly discuss Narcolepsy type 1 or narcolepsy type 2. This is addressed by Abad and Barateau.
Regarding claims 48 and 49, Abad on p. 40, sec. Diagnosis, classification, and epidemiology states “The international Classification of Sleep Disorders (ICSD-3) classifies narcolepsy into Type 1 (narcolepsy with cataplexy) and Type 2 (narcolepsy without cataplexy).” Abad continues “Narcolepsy Type 1 criteria require cataplexy plus either 1) two sleep-onset REM periods (SOREMPS) on multiple latency test (MSLT) or a SOREMP on nocturnal polysomnogram (PSG) plus one SOREMP on MSLT or 2) cerebrospinal (CSF) hypocretin-1 (hert-1) concentration ≤ 110 pg/mL or <1/3 of mean values obtained in normal subjects with same standardized assay in addition to EDS.
Barateau teaches broadly to treatment options for narcolepsy (title). Barateau on p. 373, sec. Treatment options for Narcolepsy Type 2 states “To our knowledge, no pharmacological study has focused exclusively on patients with NT2; however, most studies conducted in narcolepsy included patients with and without cataplexy. Current medications and guidelines to treat EDS and symptoms associated with REM sleep dysregulation or disturbed nocturnal sleep in NT2 should be the same as for NT1.”
Naganuma teaches that inhibition of MCH in an effective method of treating symptoms of narcolepsy and cataplexy. Guzzo teaches compounds that are taught to be strong MCH antagonists. Abad teaches that narcolepsy type 1 and type 2 are distinct conditions, but Barateau teaches that treatment of both conditions is the same. Therefore, one of ordinary skill in the art would have found it prima facie obvious at the time of the effective filing date to have combined Naganuma with Guzzo, Abad, and Barateau to arrive at the instant claims with a reasonable assumption of success. One of ordinary skill in the art would have found motivation to make the combination as the Naganuma teaches MCH antagonism is effective for treating symptoms of narcolepsy and cataplexy.
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 35, 37, 44-46, 48-49, and 56 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 and 34-37 of U.S. Patent No. 9,650,378 in view of Naganuma (Neurobiology of Disease 120, 2018, 12-20) in view of Abad (Nature and Science of Sleep, 2017:9 39-57) and Barateau (CNS Drugs, 2016, 30:369-379).
The reference claims are drawn to compounds of a formula I shown below.
Guzzo Formula I
PNG
media_image3.png
238
332
media_image3.png
Greyscale
Reference claim 21 claims the following compound.
Guzzo Claim 21 compound
PNG
media_image4.png
156
316
media_image4.png
Greyscale
Guzzo in col. 313 states that the compounds of Formula I are “compounds that bind strongly to MCH1”. Naganuma teaches a method of treating narcolepsy that involves administration of an MCH antagonist. One of ordinary skill in the art would find it obvious to modify the method of Naganuma by using the compound of Guzzo as Guzzo teaches that its compounds “strongly bind to MCH” and are “melanin-concentrating hormone (MCH1) receptor-selective antagonists”.
Response to Arguments
Applicant’s arguments have been considered but are not persuasive.
Applicant states that i) Guzzo does not motivate selection of the claimed compound, ii) Naganuma does not support substitution of SNAP 94847 for the compound of Guzzo, and ii) there is not reasonable expectation of success.
Applicant states” “TABLE 1 lists 147 different compounds, all described as meeting the same threshold binding criterion. Guzzo does not identify, highlight, or ascribe any particular significance to Compound 49 relative to the other 146 structurally distinct compounds. In view of this breadth, there is no basis to conclude that a person of ordinary skill in the art would have been motivated to single out Compound 49, let alone to use it in a therapeutic method…”.
Regarding Naganuma, applicant states “Although Naganuma identifies SNAP 94847 as an MCH inhibitor and correlates MCH inhibition with these effects, it provides no basis for concluding that any other MCH inhibitor could be successfully used. A person of ordinary skill in the art would not reasonably infer that SNAP 94847 could be substituted with a structurally unrelated compound from Guzzo. Fundamental principles of medicinal chemistry including structure-activity relationships, bioavailability, metabolic stability, blood-brain bearer penetration, and receptor selectivity – known to significantly vary between compounds having very different structures – would instead counsel skepticism in the person of ordinary skill in the art, particularly where the proposed substitute…belongs to a different chemical class than SNAP 94847.”
Regarding the expectation of success, applicant states “The mere disclosure in Guzzo that Compound 49 has an inhibitory constant (Ki) of
≤
3.5 μM in an MCH1 binding assay does not supply motication or a reasonable expectation of success in replacing SNAP94847…To the contrary, SNAP 94847 has been reported to have a Ki of approximately 2.2 nM which is roughly 1,600-fold (three-order-of-magnitude) greater potency than the binding threshold reported for the Guzzo compounds. Faced with this disparity, a person of ordinary skill in the art would not be motivated to replace SNAP 94847 with a Guzzo compound, nor reasonably expect such a substitution to succeed.”
The election of Guzzo’s compound does not require that the single compound have a distinguishing feature from the other compounds listed. The disclosure of the compound via Guzzo is evidence that the compound was known within the art at the time of filing. The other critical feature that is disclosed by Guzzo is the Ki data which shows that Guzzo’s compound 49 exhibits a Ki of 3.5 μM. Compared to SNAP 94847, which as applicant as stated has a Ki of 2.2 nM for MCH1 receptor, one of ordinary skill would recognize the substantial increase in binding affinity of Guzzo’s compound 49 which, as applicant has stated, is “roughly 1,600-fold” over SNAP 94847. An explicit statement that compound 49 is an improvement over SNAP 94847 is not required as one of ordinary skill would recognize this inherent improvement. Essentially, the improvement being taught within the art is the motivation to make the substitution.
The MPEP section 2144(I) states:
I. RATIONALE MAY BE IN A REFERENCE, OR REASONED FROM COMMON KNOWLEDGE IN THE ART, SCIENTIFIC PRINCIPLES, ART-RECOGNIZED EQUIVALENTS, OR LEGAL PRECEDENT
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992); see also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000)
Naganuma is relied upon as evidence that MCH modulation affects symptoms of narcolepsy and cataplexy. The critical information is that MCH antagonism “strongly reduces both cataplexy and abnormal REM sleep transitions.” Additionally, Naganuma provides data showing SNAP 94847’s activity at the MCH receptor. Where this overlaps with Guzzo is that Guzzo in col. 1, l. 56-59 discloses, “Disruption of the binding between MCH and the MCH receptor, i.e. MCH antagonism, may thus be used to counteract the effects of MCH.” Additionally, Guzzo discloses the activity of compound 49 at the MCH receptor as well.
Both SNAP 94847 and compound 49 are known to bind to MCH receptor (act as MCH antagonists). Therefore, one of ordinary skill would recognize that both compounds share the same utility (MCH antagonism).
The MPEP sec. 2144.06(II) states
II. SUBSTITUTING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
In order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents. In re Ruff, 256 F.2d 590, 118 USPQ 340 (CCPA 1958) (The mere fact that components are claimed as members of a Markush group cannot be relied upon to establish the equivalency of these components. However, an applicant’s expressed recognition of an art-recognized or obvious equivalent may be used to refute an argument that such equivalency does not exist.); Smith v. Hayashi, 209 USPQ 754 (Bd. of Pat. Inter. 1980) (The mere fact that phthalocyanine and selenium function as equivalent photoconductors in the claimed environment was not sufficient to establish that one would have been obvious over the other. However, there was evidence that both phthalocyanine and selenium were known photoconductors in the art of electrophotography. "This, in our view, presents strong evidence of obviousness in substituting one for the other in an electrophotographic environment as a photoconductor." 209 USPQ at 759.).
An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
Regarding the double patenting rejections, applicant states that i) The Office applied the incorrect legal standard and ii) There is not motivation or reasonable expectation of success.
Applicant states “The Office has not applied the proper analysis for nonstatutory double patenting. As set forth in MPEP § 804, the threshold inquiry is whether any invention claimed in the present application is anticipated by, or an obvious variation of, an invention claimed the in reference patent.”
The MPEP section 1504.06(II) states
A nonstatutory double patenting rejection applies to claims directed to the same inventive concept but with different appearances or differing scope that are patentably indistinct from each other. Nonstatutory categories of double patenting rejections which are not the "same invention" type may be overcome by the submission of a terminal disclaimer.
In determining whether a nonstatutory double patenting rejection is appropriate, the examiner must compare the overall appearance of the claimed design in the application with the overall appearance of the claimed design in the conflicting application or patent. The claim in the patent or conflicting application must be considered as a whole, i.e., the elements of the claimed design of the reference are not considered individually as they may be when establishing a prima facie case of anticipation under 35 U.S.C. 102 or obviousness under 35 U.S.C. 103. See MPEP § 804, subsection II.B. (information on the analysis for nonstatutory double patenting rejections). For example, in an obviousness analysis, after the factual inquiries mandated under Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), have been made (as with a rejection under 35 U.S.C. 103, the examiner must then determine whether the results of the inquiries support a conclusion nonstatutory double patenting. To establish nonstatutory double patenting under an obviousness analysis: (A) the conflicting design claims must have overall appearances with basically the same design characteristics; and (B) the differences between the two designs must be insufficient to patentably distinguish one design from the other. Differences may be considered patentably insufficient when they are de minimis or obvious to a designer of ordinary skill in the art. While the conflicting application or patent (if less than a year older than the application) used to establish nonstatutory double patenting is not considered "prior art," the principle involved is basically the same. See In re Zickendraht, 319 F.2d 225, 138 USPQ 22 (CCPA 1963)(see concurring opinion of Judge Rich).
In determining whether to make a nonstatutory double patenting rejection between designs having differing scope, the examiner should compare the reference claim with the application claim.
A rejection is appropriate if:
(A) The difference in scope is minor and patentably indistinct between the claims being compared;
(B) Patent protection for the design, fully disclosed in and covered by the claim of the reference, would be extended by the allowance of the claim in the later filed application; and
(C) No terminal disclaimer has been filed.
Here, the difference in scope amounts to a product (reference claims) and a method of using said product (instant claims) wherein the compound is administered. This does not sufficiently make the claims distinct as administration of the compound is implicitly present within the art.
Conclusion
No claims allowed.THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LUISALBERTO GONZALEZ whose telephone number is (571)272-1154. The examiner can normally be reached M-F 8:30-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/L.G./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
Prosecution Insights