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
Status of the Claims
Applicant’s cancellation of claims 1-7 and 13-16, as well as the addition of new claims 46-51 in the response filed on August 11th 2025 is acknowledged. Claims 28-36 and 46-51 are pending and are examined on their merits.
35 U.S.C. § 112(b) Rejections Overcome by Argument
Applicant’s argument in the response filed on August 11th 2025 are acknowledged. Applicant argues that claim 32 is directed towards the alleviation/treatment of symptoms of a developmental disorder, and not the disorder itself, and thus claim 32 is not a substantial duplicate of claim 28, upon which it depends. Applicant’s argument is found persuasive, and the 112(b) rejection over claim 32 is withdrawn.
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.
The rejection of claims 28-32 and 34-35 under 35 U.S.C. 103 as being unpatentable over Park (WO 2016/137260 A1 published on September 1st 2016) in view of Manzoni (Manzoni et al., Chapter 12 - The Endocannabinoid System in Fragile X Syndrome, Editor(s): Rob Willemsen, R. Frank Kooy, Fragile X Syndrome, Academic Press, 2017, Pages 241-259) is maintained.
The rejection of claim 36 under 35 U.S.C. 103 as being unpatentable over Park in view of Manzoni and in further view of Bear and Hagerman (Hagerman et al., Pediatrics. 2009 Jan;123(1):378-90) is maintained.
Response to Arguments
Applicant’s arguments in the response filed on August 11th 2025 are acknowledged. Applicant argues that
The combination of Park and Manzoni fail to disclose all elements of the claims.
There is no motivation to combine the two references.
Regarding applicant’s first argument, applicant argues that Park fails to describe:
The administration of a compound of chemical formula 1
A method for alleviation or treatment of developmental disorder
Regarding the administration of the compound, administration is taught throughout Park (Ex: Park, pg. 23-24). Regarding the treatment of developmental disorder, while Park does not explicitly teach the treatment of developmental disorders, Park does teach the treatment of disorders that are mediated by mGlur5. While Park’s focus is the treatment of schizophrenia (Park, claim 20), Park makes no admission or teaching away of other neurological disorders, and states that, due to the activity of the compounds as mGluR5 positive allosteric modulators, they are useful in the treatment of a variety of CNS diseases. The fact that these disorders are not explicitly delineated is an admission that one of ordinary skill in the art would not reasonably use the compounds in question for the treatment of said disorders, but only that Park is not anticipatory of such a method.
Applicant further argues that “Manzoni fails to cure Park’s deficiencies because Manzoni merely describes the endocannabinoid system in FXS” and “the endocannabinoid system has no relations to the imidazopyridine or imidazotriazine compound of chemical formula 1.” Additionally, Applicant argues that “Manzoni’s mGluR5 positive allosteric modulator is very different from the imidazopyrimidine or imidazotriazine compound of chemical formula 1.”
While Manzoni does describe the endocannabinoid system’s relation to FXS, a portion of that description is in relation to mGluR5 activity. For example:
“Endocannabinoids (eCB) primarily function as retrograde messengers in the CNS, mediating the local depression of both inhibitory and excitatory synaptic neurotransmission. eCB synthesis is initiated in the postsynaptic compartment via activation of either Gq coupled GPCRs (mGluR1/5) and/or voltage-gated calcium channels (VGCC), both leading to an increase in postsynaptic calcium concentrations.”
[Manzoni, pg. 242]
“Changes in eCB function are linked to many of the cognitive and behavioral phenotypes of FXS including: intellectual disability (Lysenko et al., 2014; Thomazeau et al., 2014), anxiety (Larrieu, Madore, Joffre, & Layé, 2012), and autism (Kerr, Downey, Conboy, Finn, & Roche, 2013). Recent work studying the role of tonic eCB signaling in the ASD-linked neuroligin mutations in mice are particularly noteworthy, since the model shares deficits in mGluRLTD (Baudouin et al., 2012).”
[Manzoni, pg. 250]
One of ordinary skill in the art would recognize that Manzoni is not merely describing the endocannabinoid system in FXS, but its relation to mGluR5, as stated in the previous action,
“An alternative, but paradoxical approach in light of the mGluR theory of FXS, would be to enhance mGluR5 function to restore DGLα coupling in the Fmr1 KO. While such a treatment might be controversial, in other nonsyndromic models of autism and cognitive dysfunction enhancement of mGluR5 function with a positive allosteric modulator normalizes physiology and behavior (Won et al., 2012).”
[Manzoni, pg. 250]
The motivation to combine Park and Manzoni does not come from the similarity of structure in their mGluR5 PAMs, but in activity. That is, one of ordinary skill in the art with the knowledge that
Park’s compounds have mGluR5 PAM activity
Park’s compounds are used to treat CNS disorders
Fragile X syndrome is mediated by mGluR5 activity and endocannabinoid activity (as described by Manzoni)
The administration of mGluR5 PAMs enhances endocannabinoid activity, is demonstrated to restore normal physiology and behavior in other CNS models, and is proposed as a treatment for FXS
would have a reasonable expectation of success in treating fragile X syndrome with Park’s compounds. Claims 28-32 and 34-36 therefore remain prima facie obvious.
As new claims 46-51 incorporate the limitations of the canceled claims 2-7, the relevant information from the previous 102 rejection has been included below, and claims 46-51 too are prima facie obvious.
35 U.S.C. § 103 Rejections Reiterated
The relevant information from the previous 102 rejection as it relates to the compounds described in claims 28 and 46-51 is shown below:
Park teaches the compound:
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192
411
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(Park, pg. 26, Ex. 2),
This compound is anticipatory of claims 1-5
Park additionally teaches the compound,
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198
422
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(Park, pg. 65, Ex. 102),
which is anticipatory of claims 6-7.
Claims 28-31 are directed towards the treatment of disorders such as fragile X syndrome via administration of the compound of claim 1. For the teachings of Park as they are directed towards the compound of claim 1, see the above 102 rejection over claim 1.
Park additionally teaches the compound’s activity as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) (Park, pg. 1), and discloses the compound’s usefulness for the treatment of disorders related to glutamate dysfunction and mGluR5 (Park, pg. 2). Park does not explicitly teach the treatment of fragile X syndrome with the compound, but one of ordinary skill in the art would have had a reasonable expectation of success in treating fragile X syndrome with the compound, because positive allosteric modulators of mGluR5 have been demonstrated in the art to restore long term synaptic depression (LTD) in neurons that have lost the capability, and have been suggested for use in normalizing physiology and behavior in the context of fragile X syndrome. See Manzoni, who teaches these deficits in the context of fragile X syndrome:
“In FXS studies of endocannabinoid regulation, inhibitory neurotransmission has predominated perhaps due to eCB-iLTD plasticity dominating in the hippocampus. However eCB regulation of excitatory neurotransmission is equally prominent in the CNS (Kano et al., 2009). Significantly monosynaptic eCB-LTD can readily be induced in many brain regions in response to synaptic stimulation (Heifets & Castillo, 2009). In the ventral striatum, notably the nucleus accumbens, eCB-LTD is expressed at glutamatergic afferents synapsing onto MSNs and requires mGluR5 activity (Robbe et al., 2002). This LTD is 2-AG mediated and results in a sustained depression of glutamate release. In Fmr1 KO mice the LTD is absent (Jung et al., 2012). Unlike inhibitory neurotransmission, Fmr1 KO MSNs show no changes in basal excitatory activity and tonic eCB signaling is unaffected (Jung et al., 2012; Neuhofer et al., 2015). Thus modulation of MSN inputs is lost in the Fmr1 KO.”
[Manzoni, pg. 249]
Manzoni further teaches positive allosteric modulators for the restoration of eCB-LTD:
“If it is the failure to achieve threshold concentrations of 2-AG that impairs eCB-LTD, a reasonable prediction is that pharmacological treatments that increase 2-AG concentrations might restore eCB function in the Fmr1 KO. Two pharmacological routes present themselves: enhancement of 2-AG synthesis and inhibition of 2-AG degradation/hydrolysis. The duration and strength of 2-AG signaling is particularly sensitive to hydrolysis by MAGL (Blankman, Simon, & Cravatt, 2007; Kano et al., 2009). Consequently we reported that blocking 2-AG degradation with the specific MAGL inhibitor JZL184 leads to a rapid recovery of eCB-LTD not only in the nucleus accumbens, but also prefrontal cortex of the Fmr1 KO mouse (Jung et al., 2012). This finding not only confirms that it is a decoupling in mGluR5-mediated 2-AG synthesis which underlies deficits in excitatory eCB-LTD, but also suggests the eCB system may be a worthy clinical target in FXS (discussed later). An alternative, but paradoxical approach in light of the mGluR theory of FXS, would be to enhance mGluR5 function to restore DGLα coupling in the Fmr1 KO. While such a treatment might be controversial, in other nonsyndromic models of autism and cognitive dysfunction enhancement of mGluR5 function with a positive allosteric modulator normalizes physiology and behavior (Won et al., 2012). Preliminary results have shown that treatment of prefrontal cortex Fmr1 KO neurons with the mGluR5 positive allosteric modulator CDPPB restores eCB-LTD (Martin and Manzoni, unpublished). Thus in the context of the endocannabinoid system, treatments that inhibit mGluR5 function might be expected to aggravate deficits in 2-AG signaling.”
[Manzoni, pg. 250]
As the compound is known as a positive allosteric modulator of mGluR5, and mGluR5 modulators are known for this activity, one of ordinary skill in the art would therefore have a reasonable expectation of success in treating fragile X syndrome with the compound of claim 1, and claims 28-31 are prima facie obvious.
Claim 32 is directed towards the method according to claim 31, which is for preventing, alleviating, or treating symptoms of developmental disorder. As the treatment of a developmental disorder would necessarily treat its symptoms, claim 32 is prima facie obvious.
Claims 34-35 limit specific aspects of the method claim 28, to a dosage of 0.1-500 mg/kg, and to administration to a mammal. Park teaches administration of the compound orally, to humans, at 0.1-500 mg/kg (Park, pg. 22, paragraph [0479]), and claims 34-35 are prima facie obvious.
Claims 33 is rejected under 35 U.S.C. 103 as being unpatentable over Park in view of Manzoni and in further view of Bear (Bear et al., Trends Neurosci. 2004 Jul;27(7):370-7).
Claim 33 further limits the symptoms in the method of claim 32 to be selected from a group, that includes seizures. For the teachings of Park and Manzoni as they relate to claim 32, see the above 103 rejection for claim 32. Bear teaches that seizures are a symptom of fragile X syndrome (Bear, pg. 374). As the treatment of fragile X syndrome with the compound is prima facie obvious, and the treatment of a condition will necessarily treat its symptoms, claim 33 is therefore prima facie obvious.
Claim 36 further limits the method of claim 36 to require administration of an additional agent, such as a stimulant. For the teachings of Park and Bear as they relate to the instant compounds and the treatment of fragile X syndrome with said compounds, see the 103 rejection for claim 28.
Regarding administration of additional compounds, stimulants, such as guanfacine are known to be administered in the treatment of fragile X syndrome, specifically in the alleviation of ADHD symptoms (Hagerman, pg. 4). As the administration of both the instant compounds and guanfacine to patients with fragile X syndrome is obvious, claims 16 and 36 are prima facie obvious.
Nonstatutory Double Patenting Rejections Maintained
Response to Arguments
Applicant’s arguments in the response filed on August 11th 2025 are acknowledged. Applicant’s arguments regarding the nonstatutory double patenting rejections rely on the nonobviousness of the method of claim 28 over the described compounds in view of Manzoni. The nonstatutory double patenting rejections are therefore maintained for the same reasons as the above 103 rejections.
Nonstatutory Double Patenting Rejections Reiterated
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 1-7 and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,745,310 (‘310 Patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘310 Patent teaches a subgenus of applicant’s compound genus.
Claims 28-32 and 34-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,745,310 in view of Manzoni (Manzoni et al., Chapter 12 - The Endocannabinoid System in Fragile X Syndrome, Editor(s): Rob Willemsen, R. Frank Kooy, Fragile X Syndrome, Academic Press, 2017, Pages 241-259).
The ‘310 Patent additionally teaches the compound’s activity as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) (‘310 Patent, col. 1), and discloses the compound’s usefulness for the treatment of disorders related to glutamate dysfunction and mGluR5 (‘310 Patent, col. 1). The ‘310 Patent does not explicitly teach the treatment of fragile X syndrome with the compound, but one of ordinary skill in the art would have had a reasonable expectation of success in treating fragile X syndrome with the compound, because positive allosteric modulators of mGluR5 have been postulated for the treatment of fragile X syndrome (see the above 103 rejection for claim 1). One of ordinary skill in the art would therefore have a reasonable expectation of success in treating fragile X syndrome with the compound of claim 1, and claims 28-31 are prima facie obvious.
Claim 32 is directed towards the method according to claim 31, which is for preventing, alleviating, or treating symptoms of developmental disorder. As the treatment of a developmental disorder would necessarily treat its symptoms, claim 32 is prima facie obvious.
Claims 34-35 limit specific aspects of the method claim 28, to a dosage of 0.1-500 mg/kg, and to administration to a mammal. The ‘310 Patent teaches administration of the compound orally, to humans, at 0.1-500 mg/kg (‘310 Patent, col. 19), and claims 34-35 are prima facie obvious.
Claim 33 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,745,310 in view of Manzoni and in further view of Bear (Bear et al., Trends Neurosci. 2004 Jul;27(7):370-7).
Claim 33 further limits the symptoms in the method of claim 32 to be selected from a group, that includes seizures, which are a symptom of fragile X syndrome (Bear, pg. 374). Claim 33 is prima facie obvious for the same reasons as claim 32.
Claims 16 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,745,310 in view of Manzoni and in further view of Bear and Hagerman (Hagerman et al., Pediatrics. 2009 Jan;123(1):378-90).
Claim 16 further limits the composition of claim 1 to require an additional agent, such as guanfacine, a stimulant. Claim 36 further limits the method of claim 36 to require administration of an additional agent, such as a stimulant. For the teachings of the ‘310 Patent and Bear as they relate to the instant compounds and the treatment of fragile X syndrome with said compounds, see the above nonstatutory double patenting rejections for claims 1 and 28.
Regarding administration of additional compounds, stimulants, such as guanfacine are known to be administered in the treatment of fragile X syndrome, specifically in the alleviation of ADHD symptoms (Hagerman, pg. 4). As the administration of both the instant compounds and guanfacine to patients with fragile X syndrome is obvious, claims 16 and 36 are prima facie obvious.
Claims 1-7 and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 11,046,702 (‘702 Patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘702 Patent teaches methods of modulating metabotropic glutamate receptor subtype 5 via administration of the genus of the ‘310 Patent, a subgenus of applicant’s compound genus.
Claims 28-32 and 34-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 11,046,702 (‘702 Patent) in view of Manzoni (Manzoni et al., Chapter 12 - The Endocannabinoid System in Fragile X Syndrome, Editor(s): Rob Willemsen, R. Frank Kooy, Fragile X Syndrome, Academic Press, 2017, Pages 241-259).
The ‘310 Patent additionally teaches the compound’s activity as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) (‘702 Patent, col. 1), and discloses the compound’s usefulness for the treatment of disorders related to glutamate dysfunction and mGluR5 (‘702 Patent, col. 1). The ‘310 Patent does not explicitly teach the treatment of fragile X syndrome with the compound, but one of ordinary skill in the art would have had a reasonable expectation of success in treating fragile X syndrome with the compound, because positive allosteric modulators of mGluR5 have been postulated for the treatment of fragile X syndrome (see the above 103 rejection for claim 1). One of ordinary skill in the art would therefore have a reasonable expectation of success in treating fragile X syndrome with the compound of claim 1, and claims 28-31 are prima facie obvious.
Claim 32 is directed towards the method according to claim 31, which is for preventing, alleviating, or treating symptoms of developmental disorder. As the treatment of a developmental disorder would necessarily treat its symptoms, claim 32 is prima facie obvious.
Claims 34-35 limit specific aspects of the method claim 28, to a dosage of 0.1-500 mg/kg, and to administration to a mammal. The ‘702 Patent teaches administration of the compound orally, to humans, at 0.1-500 mg/kg (‘702 Patent, col. 19-20), and claims 34-35 are prima facie obvious.
Claim 33 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 11,046,702 (‘702 Patent) in view of Manzoni and in further view of Bear (Bear et al., Trends Neurosci. 2004 Jul;27(7):370-7).
Claim 33 further limits the symptoms in the method of claim 32 to be selected from a group, that includes seizures, which are a symptom of fragile X syndrome (Bear, pg. 374). Claim 33 is prima facie obvious for the same reasons as claim 32.
Claims 16 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 11,046,702 (‘702 Patent) in view of Manzoni and in further view of Bear and Hagerman (Hagerman et al., Pediatrics. 2009 Jan;123(1):378-90).
Claim 16 further limits the composition of claim 1 to require an additional agent, such as guanfacine, a stimulant. Claim 36 further limits the method of claim 36 to require administration of an additional agent, such as a stimulant. For the teachings of the ‘702 Patent and Bear as they relate to the instant compounds and the treatment of fragile X syndrome with said compounds, see the above nonstatutory double patenting rejections for claims 1 and 28.
Regarding administration of additional compounds, stimulants, such as guanfacine are known to be administered in the treatment of fragile X syndrome, specifically in the alleviation of ADHD symptoms (Hagerman, pg. 4). As the administration of both the instant compounds and guanfacine to patients with fragile X syndrome is obvious, claims 16 and 36 are prima facie obvious.
Claims 1-7 and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20 and 22-38 of U.S. Patent No. 10,100,057 (‘057 Patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘057 Patent teaches methods of treating schizophrenia via administration of the genus of the ‘310 Patent, a subgenus of applicant’s compound genus.
Claims 28-32 and 34-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20 and 22-38 of U.S. Patent No. 10,100,057 (‘057 Patent) in view of Manzoni (Manzoni et al., Chapter 12 - The Endocannabinoid System in Fragile X Syndrome, Editor(s): Rob Willemsen, R. Frank Kooy, Fragile X Syndrome, Academic Press, 2017, Pages 241-259).
The ‘057 Patent additionally teaches the compound’s activity as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) (‘057 Patent, col. 1), and discloses the compound’s usefulness for the treatment of disorders related to glutamate dysfunction and mGluR5 (‘057 Patent, col. 1-2). The ‘057 Patent does not explicitly teach the treatment of fragile X syndrome with the compound, but one of ordinary skill in the art would have had a reasonable expectation of success in treating fragile X syndrome with the compound, because positive allosteric modulators of mGluR5 have been postulated for the treatment of fragile X syndrome (see the above 103 rejection for claim 1). One of ordinary skill in the art would therefore have a reasonable expectation of success in treating fragile X syndrome with the compound of claim 1, and claims 28-31 are prima facie obvious.
Claim 32 is directed towards the method according to claim 31, which is for preventing, alleviating, or treating symptoms of developmental disorder. As the treatment of a developmental disorder would necessarily treat its symptoms, claim 32 is prima facie obvious.
Claims 34-35 limit specific aspects of the method claim 28, to a dosage of 0.1-500 mg/kg, and to administration to a mammal. The ‘057 Patent teaches administration of the compound orally, to humans, at 0.1-500 mg/kg (‘057 Patent, col. 19), and claims 34-35 are prima facie obvious.
Claim 33 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20 and 22-38 of U.S. Patent No. 10,100,057 (‘057 Patent) in view of Manzoni and in further view of Bear (Bear et al., Trends Neurosci. 2004 Jul;27(7):370-7).
Claim 33 further limits the symptoms in the method of claim 32 to be selected from a group, that includes seizures, which are a symptom of fragile X syndrome (Bear, pg. 374). Claim 33 is prima facie obvious for the same reasons as claim 32.
Claims 16 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20 and 22-38 of U.S. Patent No. 10,100,057 (‘057 Patent) in view of Manzoni and in further view of Bear and Hagerman (Hagerman et al., Pediatrics. 2009 Jan;123(1):378-90).
Claim 16 further limits the composition of claim 1 to require an additional agent, such as guanfacine, a stimulant. Claim 36 further limits the method of claim 36 to require administration of an additional agent, such as a stimulant. For the teachings of the ‘057 Patent and Bear as they relate to the instant compounds and the treatment of fragile X syndrome with said compounds, see the above nonstatutory double patenting rejections for claims 1 and 28.
Regarding administration of additional compounds, stimulants, such as guanfacine are known to be administered in the treatment of fragile X syndrome, specifically in the alleviation of ADHD symptoms (Hagerman, pg. 4). As the administration of both the instant compounds and guanfacine to patients with fragile X syndrome is obvious, claims 16 and 36 are prima facie obvious.
Claims 1-7 and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 12,037,338 (‘338 Patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘702 Patent teaches methods of modulating metabotropic glutamate receptor subtype 5 via administration of the genus of the ‘310 Patent, a subgenus of applicant’s compound genus.
Claims 28-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 12,037,338 (‘338 Patent in view of Manzoni (Manzoni et al., Chapter 12 - The Endocannabinoid System in Fragile X Syndrome, Editor(s): Rob Willemsen, R. Frank Kooy, Fragile X Syndrome, Academic Press, 2017, Pages 241-259).
The ‘338 Patent additionally teaches the compound’s activity as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) (‘338 Patent, col. 1), and discloses the compound’s usefulness for the treatment of disorders related to glutamate dysfunction and mGluR5 (‘338 Patent, col. 1-2). The ‘338 Patent does not explicitly teach the treatment of fragile X syndrome with the compound, but one of ordinary skill in the art would have had a reasonable expectation of success in treating fragile X syndrome with the compound, because positive allosteric modulators of mGluR5 have been postulated for the treatment of fragile X syndrome (see the above 103 rejection for claim 1). One of ordinary skill in the art would therefore have a reasonable expectation of success in treating fragile X syndrome with the compound of claim 1, and claims 28-31 are prima facie obvious.
Claim 32 is directed towards the method according to claim 31, which is for preventing, alleviating, or treating symptoms of developmental disorder. As the treatment of a developmental disorder would necessarily treat its symptoms, claim 32 is prima facie obvious.
Claims 34-35 limit specific aspects of the method claim 28, to a dosage of 0.1-500 mg/kg, and to administration to a mammal. The ‘338 Patent teaches administration of the compound orally, to humans, at 0.1-500 mg/kg (‘338 Patent, col. 19-20), and claims 34-35 are prima facie obvious.
Claim 33 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 12,037,338 (‘338 Patent) in view of Manzoni and in further view of Bear (Bear et al., Trends Neurosci. 2004 Jul;27(7):370-7).
Claim 33 further limits the symptoms in the method of claim 32 to be selected from a group, that includes seizures, which are a symptom of fragile X syndrome (Bear, pg. 374). Claim 33 is prima facie obvious for the same reasons as claim 32.
Claims 16 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-39 of U.S. Patent No. 12,037,338 (‘338 Patent) in view of Manzoni and in further view of Bear and Hagerman (Hagerman et al., Pediatrics. 2009 Jan;123(1):378-90).
Claim 16 further limits the composition of claim 1 to require an additional agent, such as guanfacine, a stimulant. Claim 36 further limits the method of claim 36 to require administration of an additional agent, such as a stimulant. For the teachings of the ‘338 Patent and Bear as they relate to the instant compounds and the treatment of fragile X syndrome with said compounds, see the above nonstatutory double patenting rejections for claims 1 and 28.
Regarding administration of additional compounds, stimulants, such as guanfacine are known to be administered in the treatment of fragile X syndrome, specifically in the alleviation of ADHD symptoms (Hagerman, pg. 4). As the administration of both the instant compounds and guanfacine to patients with fragile X syndrome is obvious, claims 16 and 36 are prima facie obvious.
Claims 1-7 and 13-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21-39 of copending Application No. 18/734,144 (‘144 Application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘144 Application teaches a subgenus of applicant’s compound genus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 28-32 and 34-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21-39 of copending Application No. 18/734,144 (‘144 Application) in view of Manzoni (Manzoni et al., Chapter 12 - The Endocannabinoid System in Fragile X Syndrome, Editor(s): Rob Willemsen, R. Frank Kooy, Fragile X Syndrome, Academic Press, 2017, Pages 241-259).
The ‘338 Patent additionally teaches the compound’s activity as a positive allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5) (‘144 Application, paragraph [0005]), and discloses the compound’s usefulness for the treatment of disorders related to glutamate dysfunction and mGluR5 (‘144 Application, paragraph [0006]). The ‘144 Application does not explicitly teach the treatment of fragile X syndrome with the compound, but one of ordinary skill in the art would have had a reasonable expectation of success in treating fragile X syndrome with the compound, because positive allosteric modulators of mGluR5 have been postulated for the treatment of fragile X syndrome (see the above 103 rejection for claim 1). One of ordinary skill in the art would therefore have a reasonable expectation of success in treating fragile X syndrome with the compound of claim 1, and claims 28-31 are prima facie obvious.
Claim 32 is directed towards the method according to claim 31, which is for preventing, alleviating, or treating symptoms of developmental disorder. As the treatment of a developmental disorder would necessarily treat its symptoms, claim 32 is prima facie obvious.
Claims 34-35 limit specific aspects of the method claim 28, to a dosage of 0.1-500 mg/kg, and to administration to a mammal. The ‘144 Application teaches administration of the compound orally, to humans, at 0.1-500 mg/kg (‘144 Application, paragraph [0458]), and claims 34-35 are prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Claim 33 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21-39 of copending Application No. 18/734,144 (‘144 Application) in view of Manzoni and in further view of Bear (Bear et al., Trends Neurosci. 2004 Jul;27(7):370-7).
Claim 33 further limits the symptoms in the method of claim 32 to be selected from a group, that includes seizures, which are a symptom of fragile X syndrome (Bear, pg. 374). Claim 33 is prima facie obvious for the same reasons as claim 32.
Claims 16 and 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 21-39 of copending Application No. 18/734,144 (‘144 Application) in view of Manzoni and in further view of Bear and Hagerman (Hagerman et al., Pediatrics. 2009 Jan;123(1):378-90).
Claim 16 further limits the composition of claim 1 to require an additional agent, such as guanfacine, a stimulant. Claim 36 further limits the method of claim 36 to require administration of an additional agent, such as a stimulant. For the teachings of the ‘144 Application and Bear as they relate to the instant compounds and the treatment of fragile X syndrome with said compounds, see the above nonstatutory double patenting rejections for claims 1 and 28.
Regarding administration of additional compounds, stimulants, such as guanfacine are known to be administered in the treatment of fragile X syndrome, specifically in the alleviation of ADHD symptoms (Hagerman, pg. 4). As the administration of both the instant compounds and guanfacine to patients with fragile X syndrome is obvious, claims 16 and 36 are prima facie obvious.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629