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 .
Status of the Application
Claims 28-30, 33-36 and 49-54 are pending in the application as of the response filed 05/19/2026. Claim 1-27, 31-32 and 37-48 are cancelled. The examiner notes that there are no claim amendments in the response dated 05/19/2026. Claims 28-30, 33-36 and 49-54 are examined herein.
Applicant’s submission of an English translation of the foreign priority application filed in Korea, is acknowledged and accepted. The subject matter of the instant claims have support in the foreign priority application. Accordingly, claims 28-30, 33-36 and 49-54 have an effective filing date of 10/21/2019.
Applicant’s arguments have been carefully considered but were not found to be persuasive, as is elaborated below.
In view of the pending claims, the 35 U.S.C. 103 rejections of previous record are maintained. The non-statutory double patenting rejection over co-pending Application No 18/734,144 is rendered moot in consideration of the abandonment of the reference ‘144 application. All other non-statutory double patenting rejections of previous record are maintained and updated.
Claim Rejections - 35 USC § 103 - Maintained
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.
Claims 28-30, 33-36 and 49-54 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (WO 2016/137260 A1, 01 September 2016, hereinafter Park, of previous record) in view of Conn et al. (WO 2012/125732 A1, 20 September 2012, hereinafter Conn, in the IDS).
Regarding instant claims 28, 33-35 and 49-54, Park teaches a method for the prevention and/or treatment of disorders mediated by glutamate dysfunction and mGluR5, comprising the step of administering a therapeutically effective amount of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof to a patient in need thereof (Paras. [481]-[482]; Paras. [9]-[19]). Park teaches the salts include solvates and hydrates (Para. [474]).
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Park teaches the following exemplary compounds of Example 2 (Paras. [516]-[520]) and Example 102 (Paras. [1095]-[1098]).
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Example 2 Example 102
The above compounds fall within the scope of instant Chemical Formula 1 wherein
X is CH;
Z is O;
R1 is C6 aryl – unsubstituted phenyl (Example 2), fluoro substituted phenyl (Example 102);
R2 is C6 aryl – unsubstituted phenyl (Example 2), 6-membered unsaturated heterocyclyl having 1 N heteroatom (pyridyl) (Example 102).
The above compounds further fall within the scope of instant claims 49, 50, 51, 52, 53, 54 (6-(4-fluorophenyl)-2-(pyridin-2-yloxymethyl)imidazo[1,2-a]pyrimidine).
Park teaches treating a cognitive disorder such as schizophrenia (Para. [482]). Park teaches the compounds act as positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5) (Para. [7]; Para. [468]; Para. [498]; Paras. [1687]-[1696]; Table 1). Park teaches glutamate is the most prevalent excitatory neurotransmitter in the central nervous system (CNS) of mammals and plays an important role in numerous physiological functions such as perception and recognition, and synaptogenesis as well as learning and memory (Para. [2]). Park teaches modulators of mGluR5 receptors could be therapeutically beneficial in the treatment of various CNS diseases (Para. [5]). Park teaches the patient may be a mammal, preferably a human (Para. [482]). Park teaches an effective amount of 0.1 to 500 mg/kg (body weight), preferably 0.5 to 100 mg/kg (body weight) per day in case of mammals including a human, of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt (Para. [479]).
Park do not teach wherein the disease associated with cognitive disorder is selected from the group consisting of mild cognitive impairment, Alzheimer's disease, Alzheimer type dementia, presenile dementia, early onset Alzheimer's disease, senile dementia, Lewy body corpuscle dementia, micro-infarct dementia, AIDS-related dementia, HIV-dementia, dementia associated with Lewy bodies, Down's syndrome associated dementia, Pick's disease, recent short-term memory impairment, age-associated cognitive disorder, age-associated memory impairment, drug-associated cognitive disorder, immunodeficiency syndrome-associated cognitive disorder, vascular disease-associated cognitive impairment, Parkinson's disease-associated cognitive impairment, cognitive disorders associated with epilepsy, depression-associated cognitive disorder, cognitive disorders associated with bipolar disorder, obsessive compulsive disorder-associated cognitive disorder, post-traumatic stress disorder, attention deficit disorder, attention deficit hyperactivity disorder, and learning deficit disorder.
Conn teaches methods of treating, preventing, ameliorating, controlling or reducing the risk of a variety of neurological disorders associated with glutamate dysfunction, facilitated by the neuromodulatory effect of allosteric modulators of mGluR5, e.g. positive allosteric modulators thereof (Para. [00352]). Conn teaches disorders associated with glutamate dysfunction that can be treated with positive allosteric modulators is a central nervous system disorder, such as a cognitive disorder selected from the group of … dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia and mild cognitive impairment (Para. [00369]; Para. [00446]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia (including AIDS-induced dementia), Alzheimer's disease, … cognitive disorders, … anxiety (including generalized anxiety disorder, panic disorder, and obsessive compulsive disorder), mood disorders (including depression, mania, bipolar disorders), … attention deficit/hyperactivity disorder, and conduct disorder (Para. [00353]; Para. [00359]; Paras. [00368]-[00369]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia, delirium, amnestic disorders, age-related cognitive decline (Para. [00356]), posttraumatic stress disorder (Para. [00358]; Para. [00360]). Conn teaches enhancing cognition in a mammal comprising administering the positive allosteric modulators of mGluR5 (Para. [0028]). Conn teaches an allosteric potentiator does not induce desensitization of the receptor and activity of a compound as an mGluR5 receptor allosteric potentiator provides advantages of increased safety margin, higher tolerability, diminished potential for abuse, reduced toxicity and rapid onset of action over the use of a pure mGluR5 receptor allosteric agonist (Paras. [0056]-[0058]). The methods of Conn relate to the treatment of mammals (Para. [0060]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Park and Conn, to have utilized the compounds of Chemical Formula (1) of Park, taught to be positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5), in the treatment of conditions associated with cognitive disorder, wherein the subject is a mammal, to arrive at the method of the instant claims with a reasonable and predictable expectation of success.
Park teaches a method for the prevention and/or treatment of disorders mediated by glutamate dysfunction and mGluR5, comprising the step of administering a therapeutically effective amount of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof to a patient in need thereof. Compounds of Chemical Formula (1) of Park anticipate the instant compounds of Chemical Formula 1 and are positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5). Park teaches treating a cognitive disorder such as schizophrenia. Park teaches glutamate is the most prevalent excitatory neurotransmitter in the central nervous system (CNS) of mammals and plays an important role in numerous physiological functions such as perception and recognition, and synaptogenesis as well as learning and memory. Park teaches modulators of mGluR5 receptors could be therapeutically beneficial in the treatment of various CNS diseases. Conn teaches methods of treating, preventing, ameliorating, controlling or reducing the risk of a variety of neurological disorders associated with glutamate dysfunction, facilitated by the neuromodulatory effect of allosteric modulators of mGluR5, e.g. positive allosteric modulators thereof. Conn teaches disorders associated with glutamate dysfunction that can be treated with positive allosteric modulators is a central nervous system disorder, such as a cognitive disorder selected from the group of … dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia and mild cognitive impairment. Conn teaches other conditions that are amenable to treatment with positive allosteric modulators include dementia (including AIDS-induced dementia), Alzheimer's disease, attention deficit/hyperactivity disorder, conduct disorder, amnestic disorders, age-related cognitive decline, posttraumatic stress disorder (PTSD) and obsessive compulsive disorder (OCD). Conn teaches an allosteric potentiator does not induce desensitization of the receptor and activity of a compound as an mGluR5 receptor allosteric potentiator provides advantages of increased safety margin, higher tolerability, diminished potential for abuse, reduced toxicity and rapid onset of action over the use of a pure mGluR5 receptor allosteric agonist.
It is clear that Park teaches a method of treating a CNS condition by administering a therapeutically effective amount of a positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5) compound, wherein the compound anticipates the instant compounds. Conn teaches various conditions that are responsive to the neuromodulatory effect of positive allosteric modulators of mGluR5. Conn lists the conditions include dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia, mild cognitive impairment, dementia (including AIDS-induced dementia), Alzheimer's disease, attention deficit/hyperactivity disorder, conduct disorder, amnestic disorders, age-related cognitive decline, posttraumatic stress disorder (PTSD) and obsessive compulsive disorder (OCD). Therefore, one of ordinary skill in the art would have been motivated to utilize the method of Park in the treatment of a disease associated with cognitive disorder as instantly claimed. The motivation being extend the advantageous effects of the positive allosteric modulators of mGluR5 to the treatment of other CNS diseases (Conn, Paras. [0056]-[0058]).
Regarding instant claims 29-30, the combined teachings of Park and Conn render the method of instant claim 28, prima facie obvious. The combined teachings of Park and Conn render the active step of administering the same composition (i.e., an imidazopyrimidine or imidazotriazine compound of Chemical Formula 1) to the same patient population (i.e., a subject with a disease associated with a cognitive disorder). In the absence of evidence to the contrary, the method of Park, when practiced in treating a subject afflicted with a disease associated with a cognitive disorder or for improving cognitive function (in view of Conn) would have necessarily resulted in the same treatment effects, i.e., alleviated or treated symptoms associated with the disease.
Moreover, Conn teaches “treatment” by the positive allosteric modulation of metabotropic glutamate receptor activity (mGluR5), includes palliative treatment, i.e., symptom relief (Para. [0061]; [00437]). Conn teaches treatment by positive allosteric modulation mGluR5 includes disorders or conditions comprising as a symptom a deficiency in attention and/or cognition (Paras. [00446]-[00447]).
Therefore, the limitations of instant claims 29-30 drawn to treating the symptoms are rendered prima facie obvious.
Regarding instant claim 36, the combined teachings of Park and Conn render the method of instant claim 28, prima facie obvious. Park do not teach wherein one or more drugs selected from the group consisting of dimethylamylamine, methylphenidate, amphetamine, tacrine, rivastigmine, galantamine, donepezil, memantine, tolcapone, levodopa, atomoxetine, clonidine, pramipexole, guanfacine, and fexofenadine are additionally administered.
Conn teaches the compounds can be used as single agents or in combination with one or more other drugs in the treatment, prevention, control, amelioration or reduction of risk of diseases, disorders and conditions, wherein the combination results in safer and more efficacious treatment than the single agents alone (Para. [00380]). Conn teaches the coadministration with various additional therapeutic agents (Para. [00381]-[00382]) including levodopa (Para. [00383]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Park and Conn, to have further used combination therapy in the treatment of disorders mediated by glutamate dysfunction mGluR5, as taught by Conn to arrive at the method of instant claim 36, with a reasonable expectation of success. The motivation being to effect a more efficacious treatment (Conn, Para. [00380]).
Response to Arguments
Applicants argue in pages 2-4 of the response dated 05/19/2026 that “A. There is no motivation to combine … Park is directed to imidazopyrimidine and imidazotriazine derivatives, which are PAMs of mGluR5. (Park, Abstract.) Further, Park describes pharmaceutical compositions for prevention and/or treatment of disorders mediated by glutamate and mGluR5, such as schizophrenia. (Id., para. [0472].) However, Park does not teach or suggest improvement of cognitive function … Specifically, Park and Conn are directed to structurally distinct compounds … Moreover, there is no teaching or suggestion to modify Park's compounds to incorporate the specific structural features of Conn, particularly given that both already describe mGluR5 PAMs independently. Accordingly, the PHOSITA would have had no motivation to apply Conn's teachings to Park”.
Applicant's arguments have been fully considered but they are not persuasive.
As discussed in the 103 rejection above, Park teaches a method for the prevention and/or treatment of disorders mediated by glutamate dysfunction and mGluR5, comprising the step of administering a therapeutically effective amount of the compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof to a patient in need thereof (the compound of Chemical Formula (1) of Park anticipates the instantly claimed compound of Chemical Formula 1). Park teaches the compounds act as positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5). Park teaches glutamate plays an important role in numerous physiological functions such as perception and recognition, as well as learning and memory. Park teaches treating a cognitive disorder such as schizophrenia. Conn teaches disorders associated with glutamate dysfunction can be treated with positive allosteric modulators of mGluR5. Conn teaches treating a central nervous system disorder, such as a cognitive disorder selected from the group of … dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia and mild cognitive impairment and other cognitive disorders comprising administering the positive allosteric modulators of mGluR5. Conn teaches enhancing cognition in a mammal comprising administering the positive allosteric modulators of mGluR5. Therefore, the teachings of Conn provide sufficient motivation to a PHOSITA to treat a disease associated with cognitive disorder and/or enhance cognition (i.e., improve cognitive function) by administering the compound of Chemical Formula (1) of Park, since the compound of Chemical Formula (1) of Park is taught to act as positive allosteric modulators of mGluR5 and Conn teaches cognitive disorders of the CNS to be associated with glutamate dysfunction that can be treated with positive allosteric modulators of mGluR5.
With regard to Applicant’s contention that “Park and Conn are directed to structurally distinct compounds … Moreover, there is no teaching or suggestion to modify Park's compounds to incorporate the specific structural features of Conn, particularly given that both already describe mGluR5 PAMs independently”, the examiner notes the following.
According to MPEP 2144(I), “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) (setting forth test for implicit teachings)”. As acknowledged by Applicants, both the Park and Conn references describe positive allosteric modulation of mGluR5 with respect to treatment of certain disorders. In the instant case, the Conn reference is relied upon to establish that diseases associated with cognitive disorder as recited by the instant claims can be treated by positive allosteric modulation of mGluR5 (i.e., are amenable to treatment by the same mechanism of action), thereby rendering the instant method claims prima facie obvious.
Applicants argue in pages 4-5 of the response dated 05/19/2026 that “B. There is no reasonable expectation of success …Conn describes a structurally distinct chemical formula from Park and provides only genus-level disclosure on disorders and conditions for compounds of Conn's chemical formula. In contrast, the present Specification shows that the compounds of the recited Chemical Formula I demonstrate unexpected improvements in cognitive abilities. Specifically, Examples 1-3 show that the method of claim 28 improves cognitive functions in rat models treated with dizocilpine and a rat model that underwent natural forgetting ”.
Applicant's arguments have been fully considered but they are not persuasive.
Regarding Applicant’s contention that there is no reasonable expectation of success, according to MPEP 2143.02(I), “The reasonable expectation of success requirement refers to "the likelihood of success" in combining or modifying prior art disclosures to meet the limitations of the claimed invention. See Elekta Ltd. v. ZAP Surgical Sys., Inc., 81 F.4th 1368, 1375, 2023 USPQ2d 1100 (Fed. Cir. 2023) and Intelligent Bio-Sys., Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359, 1367, 119 USPQ2d 1171, 1176 (Fed. Cir. 2016) … Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019)”.
In the instant case, as discussed in the above section, a PHOSITA would have had a reasonable expectation of success in arriving at the method of the instant claims from the combined teachings of Park and Conn.
Further, while the examiner appreciates the Applicant’s discussion of unexpected results in examples 1-3 of the instant specification, the examiner respectfully disagrees a sufficient showing of unexpected results for the following reasons.
According to MPEP 716.02(a)(I), “A greater than expected result is an evidentiary factor pertinent to the legal conclusion of obviousness ... of the claims at issue … Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991)”. In the instant case, the results of examples 1-3 describe the predictable result of enhancing cognition by administering the compounds of Chemical Formula (1), in light of the teachings of Park and Conn. In example 1, the test compound showed recovery of cognitive function to about 57.6–57.9% compared to the negative control (49.77%), but it did not reach or exceed the vehicle baseline (63.29%). While statistically significant versus the disease model, this partial recovery may be viewed as expected optimization or predictable reversal rather than an unexpected result. Similar results were seen in example 2. Applicants have not shown any comparison data showing how the treatment groups performed or whether the compounds reversed cognitive dysfunction better than existing compounds.
Moreover, Applicants have not shown as to how the results of the examples can be extended to the full scope of the claims drawn to a genus of compounds of Chemical Formula 1. Thus, the evidence provided by the Applicants is not commensurate in scope with the claims.
According to MPEP 716.02(d), “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”.
Therefore, the unexpected results discussed by the Applicant, does not conclusively demonstrate unexpected results to a degree greater than what would have been expected from the prior art, let alone, to an unobvious extent.
Further, as stated in MPEP 716.02(b), "[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). Here, it is Applicant’s burden to present a clear and convincing factual evidence of nonobviousness or unexpected results.
Double Patenting – Maintained and updated
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 28-30, 33-36 and 49-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 28, 34, 36 and 46-51 of co-pending Application No 17/770,704 in view of Park et al. (WO 2016/137260 A1, 01 September 2016, hereinafter Park, of previous record) and Conn et al. (WO 2012/125732 A1, 20 September 2012, hereinafter Conn, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method for improving cognitive dysfunction in a subject by administering a compound of Chemical Formula 1 to the subject in need thereof.
The instant claims are drawn to a method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject, comprising: administering to the subject a therapeutically effective amount of an imidazopyrimidine or imidazotriazine compound of Chemical Formula 1, or a pharmaceutically acceptable salt, solvate or hydrate thereof.
The claims of the reference ‘704 application are drawn to method for alleviation or treatment of developmental disorder in a subject, comprising: administering to the subject a therapeutically effective amount of an imidazopyrimidine or imidazotriazine compound of Chemical Formula 1, or a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein 0.1 to 500 mg/kg of the imidazopyrimidine or imidazotriazine compound of Chemical Formula 1 is administered.
Claims 28, and 46-51 of the reference ‘704 application disclose the compounds of instant Chemical Formula 1 of instant claims 28 and 49-54. Specifically, the species of compounds of reference claim 51 anticipates the species of compounds of instant claim 54 and the genus of Chemical Formula 1. Claims 36 of the reference ‘704 application disclose the combination therapy of instant claim 36. The ‘704 application does not teach treating a disease associated with a cognitive disorder or for improving cognitive function in a subject.
Park teaches the compounds of Chemical Formula (1) (Paras. [14]-[466]) as positive allosteric modulators of metabotropic glutamate receptor 5 activity (mGluR5) (Para. [7]; Para. [468]; Para. [498]; Paras. [1687]-[1696]; Table 1). The compounds of Chemical Formula (1) of Park anticipates the instant compounds (see 103 rejection above).
Conn teaches various disorders associated with glutamate dysfunction that can be treated with positive allosteric modulators is a central nervous system disorder, such as a cognitive disorder selected from the group of … dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia and mild cognitive impairment (Para. [00369]; Para. [00446]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia (including AIDS-induced dementia), Alzheimer's disease, … cognitive disorders, … anxiety (including generalized anxiety disorder, panic disorder, and obsessive compulsive disorder), mood disorders (including depression, mania, bipolar disorders), … attention deficit/hyperactivity disorder, and conduct disorder (Para. [00353]; Para. [00359]; Paras. [00368]-[00369]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia, delirium, amnestic disorders, age-related cognitive decline (Para. [00356]), posttraumatic stress disorder (Para. [00358]; Para. [00360]). Conn teaches treatment by positive allosteric modulation mGluR5 includes disorders or conditions comprising as a symptom a deficiency in attention and/or cognition (Paras. [00446]-[00447]).
Therefore, the teachings of the ‘704 application in view of Park and Conn render the method of the instant claims prima facie obvious.
The instant claims 28-30, 33-36 and 49-54 and claims 28, 34, 36 and 46-51 of co-pending Application No 17/770,704 are therefore not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 28-30, 33 and 49-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,745,310 B2 in view of Conn et al. (WO 2012/125732 A1, 20 September 2012, hereinafter Conn, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to compounds of Chemical Formula 1 having overlapping scope.
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The instant claims are drawn to a method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject, comprising: administering to the subject a therapeutically effective amount of an imidazopyrimidine or imidazotriazine compound of Chemical Formula 1, or a pharmaceutically acceptable salt, solvate or hydrate thereof.
The claims of the reference ‘310 patent are drawn to a compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof, with variables as defined in claim 1 of the reference ‘310 patent.
The compounds of claims 1-19 of the reference ‘310 patent anticipates the compounds of instant Chemical Formula 1 of instant claims 28 and 49-54. In accordance with MPEP 804(II)(B)(1) to ascertain the scope of reference claims drawn to a compound, looking into the disclosure of the ‘310 patent for utility of the reference compounds, the reference compounds are taught to be positive allosteric modulators of metabotropic glutamate receptor 5 activity (mGluR5) for use in the treatment of disorders mediated by glutamate dysfunction (Col. 1, Lns. 15-26; Col. 2, Lns. 15-31). The claims of the reference ‘310 patent do not teach a method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject.
Conn teaches various disorders associated with glutamate dysfunction that can be treated with positive allosteric modulators is a central nervous system disorder, such as a cognitive disorder selected from the group of … dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia and mild cognitive impairment (Para. [00369]; Para. [00446]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia (including AIDS-induced dementia), Alzheimer's disease, … cognitive disorders, … anxiety (including generalized anxiety disorder, panic disorder, and obsessive compulsive disorder), mood disorders (including depression, mania, bipolar disorders), … attention deficit/hyperactivity disorder, and conduct disorder (Para. [00353]; Para. [00359]; Paras. [00368]-[00369]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia, delirium, amnestic disorders, age-related cognitive decline (Para. [00356]), posttraumatic stress disorder (Para. [00358]; Para. [00360]). Conn teaches “treatment” by the positive allosteric modulation of metabotropic glutamate receptor activity (mGluR5), includes palliative treatment, i.e., symptom relief (Para. [0061]; [00437]). Conn teaches treatment by positive allosteric modulation mGluR5 includes disorders or conditions comprising as a symptom a deficiency in attention and/or cognition (Paras. [00446]-[00447]).
Therefore, a PHOSITA would have been motivated to utilize the compounds of the reference ‘310 patent in a method of alleviating or treating a disease associated with cognitive disorder or for improving cognitive function. Thus, the teachings of the reference ‘310 patent in view of Conn render the method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject of the instant claims prima facie obvious.
The instant claims 28-30, 33 and 49-54 and claims 1-19 of U.S. Patent No. 9,745,310 B2 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 28-30, 33 and 49-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,100,057 B2 in view of Conn et al. (WO 2012/125732 A1, 20 September 2012, hereinafter Conn, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of treating a disorder mediated by glutamate dysfunction comprising administering a therapeutically effective amount of a compound of Chemical Formula 1 having overlapping scope.
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The instant claims are drawn to a method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject, comprising: administering to the subject a therapeutically effective amount of an imidazopyrimidine or imidazotriazine compound of Chemical Formula 1, or a pharmaceutically acceptable salt, solvate or hydrate thereof.
The claims of the reference ‘057 patent are drawn to a method for treating a disorder mediated by glutamate dysfunction and metabotropic glutamate receptor subtype 5 (mGluR5), wherein the disorder is schizophrenia , comprising: administering to a subject in need thereof a therapeutically effective amount of a compound of Chemical Formula (I), with variables as defined in claim 1 of the reference ‘057 patent.
The compounds of claims 1-18 of the reference ‘057 patent anticipates the compounds of instant Chemical Formula 1 of instant claims 28 and 49-54. Specifically, the species of compounds of reference claim 18 anticipates the species of compounds of instant claim 54 and the genus of Chemical Formula 1. The claims of the reference ‘057 patent do not teach treating a disease associated with a cognitive disorder of the instant claims or improving cognitive function.
Conn teaches various disorders associated with glutamate dysfunction that can be treated with positive allosteric modulators is a central nervous system disorder, such as a cognitive disorder selected from the group of … dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia and mild cognitive impairment (Para. [00369]; Para. [00446]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia (including AIDS-induced dementia), Alzheimer's disease, … cognitive disorders, … anxiety (including generalized anxiety disorder, panic disorder, and obsessive compulsive disorder), mood disorders (including depression, mania, bipolar disorders), … attention deficit/hyperactivity disorder, and conduct disorder (Para. [00353]; Para. [00359]; Paras. [00368]-[00369]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia, delirium, amnestic disorders, age-related cognitive decline (Para. [00356]), posttraumatic stress disorder (Para. [00358]; Para. [00360]). Conn teaches “treatment” by the positive allosteric modulation of metabotropic glutamate receptor activity (mGluR5), includes palliative treatment, i.e., symptom relief (Para. [0061]; [00437]). Conn teaches treatment by positive allosteric modulation mGluR5 includes disorders or conditions comprising as a symptom a deficiency in attention and/or cognition (Paras. [00446]-[00447]).
Therefore, the teachings of the reference ‘057 patent in view of Conn render the method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject of the instant claims prima facie obvious.
The instant claims 28-30, 33 and 49-54 and claims 1-18 of U.S. Patent No. 10,100,057 B2 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Claims 28-30, 33 and 49-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,046,702 B2 in view of Conn et al. (WO 2012/125732 A1, 20 September 2012, hereinafter Conn, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of modulating metabotropic glutamate receptor subtype 5 (mGLuR5) in a subject comprising administering an effective amount of a compound of Chemical Formula 1 having overlapping scope.
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The instant claims are drawn to a method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject, comprising: administering to the subject a therapeutically effective amount of an imidazopyrimidine or imidazotriazine compound of Chemical Formula 1, or a pharmaceutically acceptable salt, solvate or hydrate thereof.
The claims of the reference ‘702 patent are drawn to a method of modulating metabotropic glutamate receptor subtype 5 (mGluR5) of a subject, comprising: administering to the subject an effective amount of a compound of Chemical Formula (1), with variables as defined in claim 1 of the reference ‘702 patent.
The compounds of claims 1-18 of the reference ‘702 patent anticipates the compounds of instant Chemical Formula 1 of instant claims 28 and 49-54. Specifically, the species of compounds of reference claim 18 anticipates the species of compounds of instant claim 54 and the genus of Chemical Formula 1. The claims of the reference ‘702 patent do not teach treating a disease associated with a cognitive disorder or improving cognitive function.
Conn teaches various disorders associated with glutamate dysfunction that can be treated with positive allosteric modulators is a central nervous system disorder, such as a cognitive disorder selected from the group of … dementia, dementia due to HIV disease, dementia due to Huntington's disease, dementia due to Parkinson's disease, dementia of the Alzheimer's type, substance-induced persisting dementia and mild cognitive impairment (Para. [00369]; Para. [00446]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia (including AIDS-induced dementia), Alzheimer's disease, … cognitive disorders, … anxiety (including generalized anxiety disorder, panic disorder, and obsessive compulsive disorder), mood disorders (including depression, mania, bipolar disorders), … attention deficit/hyperactivity disorder, and conduct disorder (Para. [00353]; Para. [00359]; Paras. [00368]-[00369]). Conn teaches the conditions amenable to treatment with positive allosteric modulators include dementia, delirium, amnestic disorders, age-related cognitive decline (Para. [00356]), posttraumatic stress disorder (Para. [00358]; Para. [00360]). Conn teaches “treatment” by the positive allosteric modulation of metabotropic glutamate receptor activity (mGluR5), includes palliative treatment, i.e., symptom relief (Para. [0061]; [00437]). Conn teaches treatment by positive allosteric modulation mGluR5 includes disorders or conditions comprising as a symptom a deficiency in attention and/or cognition (Paras. [00446]-[00447]).
Therefore, the teachings of the reference ‘702 patent in view of Conn render the method for alleviation or treatment of a disease associated with cognitive disorder, or for improving cognitive function in a subject of the instant claims prima facie obvious.
The instant claims 28-30, 33 and 49-54 and claims 1-18 of U.S. Patent No. 11,046,702 B2 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Response to Arguments
Applicants argue on pages 5-6 of the response dated 05/19/2026 that “Claim 28 recites "[a]method for alleviation or treatment of a disease associated with cognitive disorder." In contrast, claim 28 of the '704 application recites "[a]method for alleviation or treatment of developmental disorder." … Therefore, claim 28 is patentably distinct from claims 28 and 34-35 of the '704 application”. Applicants argue “The Office asserts that the claims or disclosure of '310 Patent, '702 Patent, and '057 Patent recite or set forth a compound or a method to treat disorder mediated by glutamate dysfunction and mGluR5. he Office acknowledges that none of the Patents describe treatment of a disease associated with a cognitive disorder or improving cognitive function, but asserts that Conn remedies this deficiency. However, the deficiencies of Conn are discussed above. Therefore, claim 28 is patentably distinct from the claims of the '310, '702, and '507 patents”.
Applicant's arguments have been fully considered but they are not persuasive.
Although claim 28 of the co-pending ‘704 application is amended to recite “a method for alleviation or treatment of developmental disorder”, comprising administering the instantly recited compounds of Chemical Formula 1, the claims of the co-pending ‘704 application in view of Park and Conn render the instant claims prima facie obvious. Park teaches the compounds of Chemical Formula 1 act as positive allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5). Conn establishes that diseases associated with cognitive disorder as recited by the instant claims are amenable to treatment by positive allosteric modulation of mGluR5. Therefore, a PHOSITA would be motivated to repurpose the method of the reference ‘704 application to treating diseases associated with cognitive disorder, with a reasonable expectation of success.
The claims of the reference '310, '702, and '507 patents, either disclose a compound of Chemical Formula (1) or a pharmaceutically acceptable salt thereof, taught to be positive allosteric modulators of metabotropic glutamate receptor 5 activity (mGluR5) for use in the treatment of disorders mediated by glutamate dysfunction; OR a method for treating a disorder mediated by glutamate dysfunction and metabotropic glutamate receptor subtype 5 (mGluR5), comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Chemical Formula (I); OR a method of modulating metabotropic glutamate receptor subtype 5 (mGluR5) of a subject, comprising: administering to the subject an effective amount of a compound of Chemical Formula (1).
The compound of Chemical Formula (I) of the reference patents anticipates the instant compound of Chemical Formula (I). Conn establishes that diseases associated with cognitive disorder as recited by the instant claims are amenable to treatment by positive allosteric modulation of mGluR5. Therefore, as clearly discussed above, the teachings of the reference patents in view of Conn render the instant claims prima facie obvious.
Thus, the above double patenting rejections of previous record are maintained.
Conclusion
Claims 28-30, 33-36 and 49-54 are rejected.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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