DETAILED ACTION
This Office action details a first action on the merits for the above referenced application No. Claims 4, 6-7, and 9-12 are pending in this application.
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 .
Priority
This application is a 35 USC 111(a) filing that claims benefit under 35 USC 120 as a continuation of US application No. 17/534,711 filed on 24 Nov. 2021, which is a continuation of US application No. 16/767,896 filed on 28 May 2020, which is a 35 USC 371 National Stage filing of international application No. PCT/EP2018/082649 filed on 27 Nov. 2018 and claims benefit under 35 USC 119(e) to foreign application No. EP 17204896.9 filed on 1 Dec. 2017.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11 Apr. 2024 has been considered by the examiner.
Claim Objections
Claims 9, and 11-12 are objected to because of the following informalities: In claim 9, the recitation of “administering to the subject of contacting a sample” should be “administering to the subject or contacting a sample” and “formula (I)” should be “formula (Ib)”, and in claim 11 “othosteric” should be “orthosteric”. In claim 12, the recitation of “which is a compound of formula (Ib)” should be “which is the compound of formula (Ib)”. Appropriate correction is required.
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.
Claim 11 is 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. Instant claim 11 is directed to a method for measuring the target engagement of an orthosteric modulator of D1-like receptors in a subject in need thereof but does not include a step for administering a orthosteric modulator of D1-like receptors in a subject. It is not clear if the orthosteric modulator being measured is the compound of formula (Ib) or another compound. The Examiner suggests possibly amending claim 11 to recite administering to the subject the orthosteric agonist modulator of D1-like receptors which is the compound of formula (Ib) according to Claim 4.
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 (i.e., changing from AIA to pre-AIA ) 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 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.
Claim(s) 4, 6-7, and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Coe et al. (WO 2014/078811 A1; published 15 May 2014; see IDS filed on 11 Apr. 2024).
Coe et al. teach heteroaromatic compounds and their use as dopamine D1 ligands (see title). Coe et al. teach example no 215
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as the (-) atropisomer (see pg. 166). Coe et al. teach that example 215 exhibits a human D1 receptor IC50 value of 1.06 nM and a EC50 value of 0.4 M and a % intrinsic activity of 101 (see pgs. 192, 195, and 197). Coe et al. teach that examples 1
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(pg. 74) and 21
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(see pg. 97) exhibit human D1 receptor Ki values of 27.3 nM and 36.2 nM, respectively (see pgs. 172-173). Coe et al. teach that the invention includes all pharmaceutically acceptable isotopically labeled compounds of formula I wherein one or more atoms are replaced by atoms having the same atomic number. Examples of suitable isotopes for inclusion in the compound of the invention include 3H, 11C, and 18F. Suitable positron emitting isotopes such as 11C and 18F can be useful in PET studies for examining substrate receptor occupancy (see pg. 18). Coe et al. teach pharmaceutically acceptable salts (see abstract, pg. 13). Coe et al. teach isolating the compound as an atropisomer (see pgs. 17 and 23). Coe et al. teach modulating an activity of D1 receptor in vitro or in vivo comprising contacting the D1 receptor with a compound of formula I (see pg. 34). Coe et al. teach pharmaceutical compositions comprising a pharmaceutically acceptable carrier (see pg. 32, claim 11).
Coe et al. do not each the compound of Formula (Ib) wherein the fluorine is 18F and which consists essentially of the atropisomer (-) or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable diluent or carrier. Coe et al. do not teach a method of quantification of the density of D1-like receptors in a subject or a sample or a method of PET imaging a subject.
However, it would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Coe et al. (compound 215 that consists essentially of the atropisomer (-) and pharmaceutical compositions thereof) by incorporating a 18F at the Me substituent to form [18F]FMe-215 (-) as taught by Coe et al. because it would have been expected to advantageously enable an orthosteric modulator of the D1 like receptors having high D1 binding affinity and potency and advantageously capable of PET studies for in vitro and in vivo examining target engagement of the D1 receptors.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Coe et al. (methods of PET imaging and in vivo and in vitro methods) by quantification of the density of D1-like receptors in a subject or sample or by in vivo PET imaging a subject, the methods comprising contacting/administering the obvious [18F]FMe-215 (-) to a subject or sample as taught by Coe et al. because it would have been expected to advantageously enable high sensitivity PET examination of the D1-like receptors.
Claim(s) 4, 6-7, and 9-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Coe et al. (WO 2014/078811 A1; published 15 May 2014; see IDS filed on 11 Apr. 2024), in view of Kusmierek et al. (US 2008/0096926 A1; published 24 Apr. 2008; see IDS filed on 11 Apr. 2024) and Beadle et al. (US 2014/0357664 A1; published 4 Dec. 2014; see IDS filed on 11 Apr. 2024).
Coe et al. teach as discussed above.
Coe et al. do not further teach methods of in vivo PET imaging and measuring the target engagement of an orthosteric agonist modulator of D1-like receptors in a subject in need thereof, comprising administering to the subject a compound of formula (Ib) in claim 4 or a method of in vivo quantification of the effect of D1 allosteric modulators on the D1 receptor in a subject in need thereof.
Kusmierek et al. teach the treatment of cognitive impairment using a selective dopamine D1 receptor agonist (see title). Kusmierek et al. that the dopaminergic status can be determined by determining the dopamine D1 receptor density in an individual patient, for example using PET (see [0016], [0034]). Kusmierek et al. teach the measurement of DAS-431 receptor occupancy in vivo. The purpose of this study is to measure the in vivo occupancy by potential therapeutic doses of an intravenous formulation of DAS-431 of the D1 receptor using PET imaging and the D1 receptor radiotracer [11C]NNC (see [0038]). The efficacy of treatment is evaluated by the dopamine D1 receptor binding potential (quantifying the densities of D1 receptors (see [0045]-[0047]).
Beadle et al. teach 3,4-dihydroisoquinolin-2(1H)-yl compounds (see title). Beadle et al. teach that the binding of a modulator to an allosteric (secondary) site produces a conformational change in the receptor protein that is transmitted to the ligands orthosteric primary binding site ([0003]). Beadle et al. teach compounds that are positive allosteric modulators (PAMs) of the dopamine 1 receptor (D1). As such the compounds are useful in the treatment of conditions in which D1 plays a role such as Parkinson’s disease and schizophrenia, including relief of associated symptoms such as mild cognitive impairment (see [0004]). Beadle et al. teach a human D1 receptor positive allosteric modulation assay (see [0077]-[0079]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Coe et al. by further measuring the target engagement of an orthosteric agonist modulator of D1-like receptor in a subject in need thereof comprising administering a orthosteric modulator of the D1 receptors such as a orthosteric modulator in Coe optionally before or after administering to the subject the orthosteric agonist modulator that is [18F]FMe-215 (-) as taught by Coe et al. and Kusimierek et al. because it would have been expected to advantageously enable determining receptor occupancy of the orthosteric modulator or advantageous in vivo measuring the target engagement of the orthorsteric agonist modulator of the D1-like receptor.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Coe et al. by further quantifying the effect of D1 allosteric modulators of the D1 receptor in a subject in need thereof comprising administering to the subject a detectable amount of an orthosteric agonist imaging agent of D1-like receptors which is the obvious [18F]FMe-215 (-) ; and administering to the subject a detectable amount of a compound which is an allosteric modulator of D1 receptors; imaging the subject with PET; and quantifying the effect of the D1 allosteric modulator as taught by Coe et al., Beadle et al., and Kusimierek et al. because it would have been expected to advantageously enable in vivo PET quantitation the effect of the agonist modulator on the orthosteric primary binding site.
Technical Background Material
Conn et al. (Nat. Rev. Drug Discovery; published 2009; see IDS filing 24 Nov. 2021) teach allosteric modulators of GPCRs (see title). Conn et al. teach that allosteric GPCR modulaotors exhibit one or more following properties: affinity modulation, efficacy modulation, and agonism/inverse agonism (see pg. 42). Conn et al. teach reported allosteric modulators of the dopamine D1 receptor (see table 1).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618