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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/05/2025 has been entered.
Election/Restrictions
Applicant’s election of Group (II) in the reply filed on 12/31/2024 is acknowledged with Applicant’s election of ALT-306 as the elected compound of the formula (I)
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and ALS (amyotrophic lateral sclerosis as the elected disease in the reply filed on 12/31/2024 is acknowledged and maintained.
Expansion of Election of Species Requirement
A reasonable and comprehensive search conducted by the Examiner determined that the prior art at the time of the present invention was such that it did render obvious the elected ALT-306 compound species
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. In light of this discovery, the search is expanded to compound ALT-201 as depicted below
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. However, the scope of the search and examination have not been extended to the full scope of the compound of the formulae (I).
Priority
This application is a continuation of U.S. Patent Application No. 17/811,021, filed July 6, 2022, which is a National Phase Application of PCT International Application Number PCT/US2020/022972, filed March 16, 2020, and claims the benefit of U.S. Provisional Application No. 62/820,158, filed March 18, 2019.
Claim Status
Claims 29-34, 39-41, 43-47, and 49-52 are pending. Claims 1-28, 35-38, 42, and 48 are canceled. Claims 43, 44, and 49-50 are withdrawn. Claims 29-34, 39-41, 45-47, and 51-52 are examined in accordance to the elected species and the expanded species.
Action Summary
Claims 29-34, 39-41, 45-47, and 52 rejected under 35 U.S.C. 103 as being unpatentable over Cerione et al (US2012/0220610 A1) in view of Wang et al (Brain Behav Immun. 2017 Jun 15;66:135–145) and Blasco et al (Current Medicinal Chemistry, 2014, 21, 3551-3575), are withdrawn in light of the claim amendment deleting compound ALT-59.
Claims 29-34, 39-41, 45-47, and 51-52 rejected under 35 U.S.C. 103 as being unpatentable over Cerione et al (US2012/0220610 A1) in view of Wang et al (Brain Behav Immun. 2017 Jun 15; 66:135–145) and Blasco et al (Current Medicinal Chemistry, 2014, 21, 3551-3575) as applied to Claim 51, are maintained, but modified and revisited in light of the claim amendment.
Claims 29-34, 39-41, 45-47, and 51-52 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,532,034 B2 in view of Wang et al (Brain Behav Immun. 2017 Jun 15;66:135–145) and Blasco et al (Current Medicinal Chemistry, 2014, 21, 3551-3575), are maintained, but modified and revised in light of the claim amendment.
Affidavit
The declaration by Chengliang Zhang under 37 CFR 1.132 filed 12/05/2025 is insufficient to overcome the rejection of claims 29-34, 39-41, 45-47, and 51-52.
The Declarant argues that as a general background, human glutaminase (GLS1) exists as two slice isoforms, kidney-type glutaminase (KGA) and glutaminase C (GaC), generated from the same GLS transcript. It has been well established that the entire catalytic domain is identical in both isoforms.
In response, the declarant’s argument is not persuasive. While the Examiner acknowledges the declarant’s background statement that human glutaminase (GLS1) exists as two slice isoforms, kidney-type glutaminase (KGA) and glutaminase C (GaC) and that the catalytic domain is identical in both isoforms. However, this general biological fact does not, in itself, establish that Cerione patent’s prediction of compound 968’s activity is known or obvious. The declaration does not provide sufficient evidence that the catalytic domain above would predictably lead to this glutaminase C activity.
The declarant argues that the two isoforms have identical amino acid sequences between the two isoforms between residues 1-550, which includes the glutaminase domain between residues 249-535. Accordingly, active site responsible for converting glutamine to glutamate is structurally and functionally same in these isoforms, and any effective glutaminase inhibitor will suppress the enzymatic activity of glutaminase regardless of the isoform within human glutaminase (GLS1). Therefore, the hypothesis that compound 968 selectively inhibit GAC but not KGA is incompatible with established biochemistry.
In response, the declarant’s argument is not persuasive. While the Examiner recognizes the declarant’s argument that the two isoforms have an identical catalytic domain. Thus, any inhibitor would suppress both isoforms. However, this does not support the declarant’s hypothesis that compound 968 selectively inhibits glutaminase C without affecting kidney-type glutaminase. In fact, this general sequence identity makes the selective inhibitor unpredictable. As cerione asserts.
The declarant argues these data suggest that the cell suppression observed by Cerione is not solely due to glutaminase inhibition. The inability of α-ketoglutarate to rescue 968-treated MDA-MB-231 cells, combined with the structural identity of the KGA and GAC catalytic domains and the requirement of both isoforms for glutaminase- dependent proliferation, demonstrates conclusively that compound 968 is not a glutaminase inhibitor. Its effects on growth must arise through an unrelated mechanism. Multiple independent studies have examined Compound 968 and related glutaminase inhibitors. These studies Koch 2020, Jacque 2015, and Lampa 2017) consistently show that Compound 968 does not exhibit the target-specific glutaminase inhibition reported by Cerione et al. In summary, based on my replication experiments and independent peer- reviewed evidence, I conclude that Compound 968 does not function as a glutaminase inhibitor, and therefore Cerione does not provide a credible rationale supporting the conclusion that it would have been obvious to use Compound 968 (or structurally related
compounds) to treat ALS or other diseases associated with either GAC or KGA dysregulation.
In response, the declarant’s argument is not persuasive. Although these references (Koch 2020, Jacques 2015, and Lampa 2017) are acknowledged by the Examiner, they are not considered because they were not submitted in a proper IDS as explained in MPEP 609 and MPEP 707. However, bases solely on the declarant’s summary of these references, these references do not establish that the general teaching of Cerione patent publication is unpredictable. Koch (2020) cannot be used at all, as it postdates the filing date of the instant application. In particular, Lumpa (2017) relates to a single cell line, but does not contradict Cerione’s teaching overall predictability. Likewise, Jacques (2015) does not undermine Cerione’s scope. Again. These references do not overcome the generat teaching of the Cerione’s reference. Cerione broadly discloses and specifically in figure 17 that compound 968 generally possesses glutaminase C activity for cancer treatment. Applicant appears to distinguish their modified compound (the elected compound) by focusing on specific cell lines, the general teaching of Cerione’ reference des not rely on those isolated studies alone. Instead, the Cerione’s reference broadly predicts glutaminase C activity (Fig 17) and the declarant has not shown this modification would yield a truly unexpected result. Thus, the claim remains obvious in view of the broad teaching of Cerione.
Maintained, but modified and revisited Rejection
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 non-obviousness.
Claims 29-34, 39-41, 45-47, and 51-52 are rejected under 35 U.S.C. 103 as being unpatentable over Cerione et al (US2012/0220610 A1) in view of Wang et al (Brain Behav Immun. 2017 Jun 15; 66:135–145) and Blasco et al (Current Medicinal Chemistry, 2014, 21, 3551-3575).
Cerione teaches a method of treating a subject with a condition mediated by production of glutamate from glutamine by glutaminase C, said method comprising: selecting a subject with a condition mediated by production of glutamate from glutamine by glutaminase C and
administering to said selected subject an inhibitor of glutaminase C activity under conditions effective to treat the condition mediated by production of glutamate from glutamine. Moreover, Cerione teaches the inhibitor of glutaminase C activity is preferably compound 968
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, wherein the condition is selected from the group consisting of breast cancer, lung cancer, brain cancer, pancreatic cancer, and colon cancer, and wherein said administering is performed parenterally, orally, subcutaneously, intravenously, intramuscularly, extraperitoneally, by intranasal instillation, or by application to mucous membranes. (See claims 14, 20-21, and Figure 1.) This compound is the same as ALT-59. Cerione teaches the method comprising an effective amount of the compound. (See paragraph [0133].) Cerione teaches a compound of the formula (I)
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, wherein R2a, R3a, R4a, R5a, and R6a are each independently H, halogen, NO2, OH, OR14a, —SR14a, NH2, NHR14a, NR14aR15a, R14aC(O)—, R14aOC(O)—, R14aC(O)O—, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl C1-C6 alkyl and wherein R11a, R12a, R13a, R14a, R15a, R16a, and R17a are each independently H, halogen, OH, NO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl C1-C6 alkyl, mono or polycyclic aryl. (See claim 14.) Cerione teaches the term alkyl includes methyl, ethyl, n-propyl among others and the term halogen means fluoro, chloro, bromo, and iodo. (See paragraphs [0049] & [0055].) In other words, dimethyl amino and methyl are interchangeable and hydrogen and halogen are also interchangeable.
Cerione does not teach the claimed compound.
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. In addition, Cerione does not teach ALS (amyotrophic lateral sclerosis).
Wang teaches the identification of the pathogenic role of GAC in synaptic and neuronal injury in vivo may have an important clinical implication. Glutaminase dysregulation has been implicated in various neurodegenerative and neuroinflammatory diseases such as HIV-1 associated dementia, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, as well as neuropsychiatric diseases such as schizophrenia. Our model is useful in that it provides a novel tool to assess the consequences of excess production of glutamate on brain function and the model may be used to test novel therapeutic strategies to alleviate excitotoxicity. (See second paragraph of page 10.)
Wang does not teach the claimed compound.
Blasco teaches this article provides an overview of excitotoxicity in ALS, focusing on the events that contribute to excess glutamate, how the excess might damage nerve cells, and how this information is being harnessed in the development of potential new neuroprotective agents. (See Abstract.) Moreover, Blasco teaches between 40% and 75% of patients with sporadic ALS (SALS) are estimated to have defects in glutamate transport leading to excessive extracellular glutamate levels. (See last paragraph of the right column of fifth paragraph.)
The differences between Cerione’s compound 968 and the elected compound are depicted in the shaded areas below:
Compound 968 elected claimed compound
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It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the dimethyl alkyl with a methyl and further substitute the bromine group adjacent to carbon atom that is attached to the dimethyl amino group with hydrogen to give Applicant’s claimed elected compound. One would have been motivated to do so, because Cerione teaches dimethyl amino and methyl are interchangeable at the R4a position and hydrogen and halogen are also interchangeable at R3a position.
It would have further been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the modified method taught by Cerione by including patient with ALS to give the claimed method. One would have been motivated to do so, because Cerione teaches compound 968 which is an inhibitor of glutaminase C can treat cancer, because, Wang teaches Glutaminase dysregulation has been implicated in various neurodegenerative and neuroinflammatory diseases such as amyotrophic lateral sclerosis (ALS) and the excess production of glutamate on brain function may be used to test novel therapeutic strategies to alleviate excitotoxicity, and also because Blasco teaches the events that contribute to the glutamate excess as a bioamker might contribute to damage nerve cells, and how this information is being harnessed in the development of potential new neuroprotective agents. One would reasonably expect the method of Cerione with the modified compound to effectively treat ALS in addition to cancer by inhibiting glutaminase C activity which synthesizes glutamate.
With respect to the identification of a subject in need of a compound that reduces, inhibits, delays, ameliorates, or prevents TDP-43 toxicity. The combination of Cerione, Wang, and Blasco do not teach a subject in need of a compound that reduces, inhibits, delays, ameliorates, or prevents TDP-43 toxicity. However, the subject with ALS would be considered a subject in need of the modified compound 968. The fact that the modified compound 968 taught by Cerione is the same compound claimed and the fact that the obvious subject taught by Cerione, Wang, and Blasco collectively, the identification step claimed would flow naturally from the collective teaching of Cerione, Wang, and Blasco.
Applicant’s argument presented in the modified and revisited rejection here repeats the same points made in the Affidavit’s section. Therefore, the reasoning the Examiner provided in response to the declaration applies equally here.
New Rejection necessitated by the claim amendment
Claims 29-34, 39-41, 45-46, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Cerione et al (US2012/0220610 A1) in view of Wang et al (Brain Behav Immun. 2017 Jun 15;66:135–145) and Blasco et al (Current Medicinal Chemistry, 2014, 21, 3551-3575).
Cerione teaches a method of treating a subject with a condition mediated by production of glutamate from glutamine by glutaminase C, said method comprising: selecting a subject with a condition mediated by production of glutamate from glutamine by glutaminase C and
administering to said selected subject an inhibitor of glutaminase C activity under conditions effective to treat the condition mediated by production of glutamate from glutamine. Moreover, Cerione teaches the inhibitor of glutaminase C activity is preferably this compound of page 10
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, wherein the condition is selected from the group consisting of breast cancer, lung cancer, brain cancer, pancreatic cancer, and colon cancer, and wherein said administering is performed parenterally, orally, subcutaneously, intravenously, intramuscularly, extraperitoneally, by intranasal instillation, or by application to mucous membranes. (See page 10, claims 14, 20-21, and Figure 1.) Cerione teaches the method comprising an effective amount of the compound. (See paragraph [0133].)
Cerione does not teach ALS (amyotrophic lateral sclerosis). Moreover, Cerione does not teach the expanded compound 201
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Wang teaches the identification of the pathogenic role of GAC in synaptic and neuronal injury in vivo may have an important clinical implication. Glutaminase dysregulation has been implicated in various neurodegenerative and neuroinflammatory diseases such as HIV-1 associated dementia, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, as well as neuropsychiatric diseases such as schizophrenia. Our model is useful in that it provides a novel tool to assess the consequences of excess production of glutamate on brain function and the model may be used to test novel therapeutic strategies to alleviate excitotoxicity. (See second paragraph of page 10.)
Wang does not teach the expanded compound 201.
Blasco teaches this article provides an overview of excitotoxicity in ALS, focusing on the events that contribute to excess glutamate, how the excess might damage nerve cells, and how this information is being harnessed in the development of potential new neuroprotective agents. (See Abstract.) Moreover, Blasco teaches between 40% and 75% of patients with sporadic ALS (SALS) are estimated to have defects in glutamate transport leading to excessive extracellular glutamate levels. (See last paragraph of the right column of fifth paragraph.)
Blasco does not teach the expanded compound 201.
Furthermore, in the absence of showing unobvious results, it would have been obvious to one of ordinary skill in the art at the time of the invention when faced with Cerione to make the instantly claimed derivatives of a known product. The instantly claimed compounds and prior art compounds are common derivatives known as isomers. Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09(11).
Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979).
The only structural difference between the claimed and prior art compounds and the claimed compounds is that the claimed compound has
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, whereas the prior art compound has
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The court held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.). See MPEP 2144.09 (111).
Guided by the teaching of Wynne et al, one skilled in the art would be able to make similar compounds by making isomers of the known compound. The motivation would be to prepare similar compounds that are pharmacologically active compounds that treat tuberculosis. The instant obviousness rejection is based on the close structural similarity of the instantly claimed compounds to the prior art compounds and the common utility shared among the compounds. There is an expectation among those of ordinary skill in the art that similar structural compounds will have similar properties and that modification of a known structure is mere experimentation within the means of a skilled artisan. See MPEP 2144.09(I).
It would have further been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by Cerione to include patient with ALS to give the claimed method. One would have been motivated to do so, because Cerione teaches the modified compound which is an inhibitor of glutaminase C can treat cancer, because, Wang teaches Glutaminase dysregulation has been implicated in various neurodegenerative and neuroinflammatory diseases such as amyotrophic lateral sclerosis (ALS) and the excess production of glutamate on brain function may be used to test novel therapeutic strategies to alleviate excitotoxicity, and also because Blasco teaches the events that contribute to the glutamate excess as a biomarker might contribute to damage nerve cells, and how this information is being harnessed in the development of potential new neuroprotective agents. One would reasonably expect the modified method of Cerione to effectively treat ALS in addition to cancer by inhibiting glutaminase C activity which synthesizes glutamate.
With respect to the identification of a subject in need of a compound that reduces, inhibits, delays, ameliorates, or prevents TDP-43 toxicity. The combination of Cerione, Wang, and Blasco do not teach a subject in need of a compound that reduces, inhibits, delays, ameliorates, or prevents TDP-43 toxicity. However, the subject with ALS would be considered a subject in need of compound 968, which is the same compound as ALT-59. The fact that compound 968 taught by Cerione is the same compound claimed and the fact that the obvious subject taught by Cerione, Wang, and Blasco collectively, the identification step claimed would flow naturally from the collective teaching of Cerione, Wang, and Blasco.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 29-34, 39-41, 45-47, and 51-52 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,532,034 B2 in view of Wang et al (Brain Behav Immun. 2017 Jun 15;66:135–145) and Blasco et al (Current Medicinal Chemistry, 2014, 21, 3551-3575).
The U.S. patent claim teaches a method of reducing the production of glutamate from glutamine by glutaminase C in a cancerous cell or a cancerous tissue, said method comprising:
inhibiting glutaminase C activity in the cancerous cell or cancerous tissue under conditions effective to reduce production of glutamate from glutamine, wherein said inhibiting comprises:
selecting a cancerous cell or a cancerous tissue, wherein the cancer is characterized by glutaminase C hyperactivity and/or glutaminase C overexpression;
providing an effective amount of a compound of formula (I):
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. Providing can reasonably be construed to be administering. Moreover, the U.S. patent claim teaches the compound is compound 968
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. (See claim 6) This compound is the same as ALT-59.
The U.S. patent claim does not teach ALS (amyotrophic lateral sclerosis).
Wang teaches the identification of the pathogenic role of GAC in synaptic and neuronal injury in vivo may have an important clinical implication. Glutaminase dysregulation has been implicated in various neurodegenerative and neuroinflammatory diseases such as HIV-1 associated dementia, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease, as well as neuropsychiatric diseases such as schizophrenia. Our model is useful in that it provides a novel tool to assess the consequences of excess production of glutamate on brain function and the model may be used to test novel therapeutic strategies to alleviate excitotoxicity. (See second paragraph of page 10.)
Wang does not teach the claimed compound.
Blasco teaches this article provides an overview of excitotoxicity in ALS, focusing on the events that contribute to excess glutamate, how the excess might damage nerve cells, and how this information is being harnessed in the development of potential new neuroprotective agents. (See Abstract.) Moreover, Blasco teaches between 40% and 75% of patients with sporadic ALS (SALS) are estimated to have defects in glutamate transport leading to excessive extracellular glutamate levels. (See last paragraph of the right column of fifth paragraph.)
Blasco does not teach the claimed compound.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the method taught by the U.S. patent claim to include patient with ALS to give the claimed method. One would have been motivated to do so, because the U.S. patent claim teaches compound 968 which is an inhibitor of glutaminase C can treat cancer, because, Wang teaches Glutaminase dysregulation has been implicated in various neurodegenerative and neuroinflammatory diseases such as amyotrophic lateral sclerosis (ALS) and the excess production of glutamate on brain function may be used to test novel therapeutic strategies to alleviate excitotoxicity, and also because Blasco teaches the events that contribute to the glutamate excess as a bioamker might contribute to damage nerve cells, and how this information is being harnessed in the development of potential new neuroprotective agents. One would reasonably expect the method of the U.S. patent claim to effectively treat ALS in addition to cancer by inhibiting glutaminase C activity which synthesizes glutamate.
With respect to the identification of a subject in need of a compound that reduces, inhibits, delays, ameliorates, or prevents TDP-43 toxicity. The combination of the U.S. patent claim, Wang, and Blasco do not teach a subject in need of a compound that reduces, inhibits, delays, ameliorates, or prevents TDP-43 toxicity. However, the subject with ALS would be considered a subject in need of compound 968, which is the same compound as ALT-59. The fact that compound 968 taught by the U.S. patent claim is the same compound claimed and the fact that the obvious subject taught by U.S. patent claim, Wang, and Blasco collectively, the identification step claimed would flow naturally from the collective teaching of U.S. patent claim, Wang, and Blasco.
With respect to claim 51, the U.S. patent claim, Wang, and Blasco collectively do not teach the elected compound. However, U.S. patent claim teaches a compound of the formula (I)
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, wherein R2a, R3a, R4a, R5a, and R6a are each independently H, halogen, NO2, OH, OR14a, —SR14a, NH2, NHR14a, NR14aR15a, R14aC(O)—, R14aOC(O)—, R14aC(O)O—, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl C1-C6 alkyl and wherein R11a, R12a, R13a, R14a, R15a, R16a, and R17a are each independently H, halogen, OH, NO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, aryl C1-C6 alkyl, mono or polycyclic aryl. (See claim 14.) U.S. patent claim teaches the term alkyl refers to methyl, ethyl, n-propyl among others and the term halogen means fluoro, chloro, bromo, and iodo. (See paragraphs [0049] & [0055].) In other words, dimethyl amino and methyl are interchangeable and hydrogen and halogen are also interchangeable.
The differences between compound 968 of the U.S. patent claim and the elected compound are depicted in the shaded areas below:
Compound 968 elected claimed compound
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It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the dimethyl alkyl with a methyl of compound 968 and further substitute the bromine group adjacent to carbon atom that is attached to the dimethyl amino group with hydrogen of compound 968 to give Applicant’s claimed elected compound. One would have been motivated to do so, because U.S. patent claim teaches dimethyl amino and methyl are interchangeable at the R4a position and hydrogen and halogen are also interchangeable at R3a position.
Applicant’s argument presented in the modified and revisited rejection here repeats the same points made in the Affidavit’s section. Therefore, the reasoning the Examiner provided in response to the declaration applies equally here.
Conclusion
Claims 29-34, 39-41, 45-47, and 51-52 are not allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628