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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/09/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
Claims 59-77 are pending in this application. Claims 1-58 and 78-137 have been cancelled by applicant.
Claim Interpretation
Claim 66 has the limitation: “benzodiazepines”. The specification mentions benzodiazepines can be alprazolam, diazepam, or chlordiazepoxide (page 7, lines 20-21). For the purposes of applying art, the limitation of “benzodiazepines” will be understood as any one of alprazolam, diazepam, or chlordiazepoxide.
Claim 66 has the limitation: “nonbenzodiazepines”. The specification mentions nonbenzodiazepines can be eszopiclone or zolpidem (page 7, line 25). For the purposes of applying art, the limitation of “nonbenzodiazepines” will be understood as any one of eszopiclone or zolpidem.
Claim 66 has the limitation: “quinazolinones”. The specification mentions quinazolinones can be diproqualone, etaqualone, or methaqualone (page 8, line 1). For the purposes of applying art, the limitation of “quinazolinones” will be understood as any one of diproqualone, etaqualone, or methaqualone.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 59-63, 67, 69-71, 74-75, and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Duke et al. (J. of Neurochem., 75, 2000, 2602-2610 – previously cited) (“Duke”); in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50 – previously cited) (“Bjurstöm”); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020 – previously cited) (“Tang”).
Regarding claim 59, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
While Duke does not teach: (i) the treatment of a coronavirus induced medical condition comprising administering to a patient an effective amount of a GABA receptor agonist; (ii) SARS-CoV or SARS-CoV-2 (claims 69-70); (iii) wherein the medical condition could result in illness, fever, pneumonia, etc. (claim 71); or (iv) administration of an additional anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77), the teachings of Bjurstöm and Tang are relied upon for these disclosures.
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract).
Therefore, regarding claim 59, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer GABA inhibitors, such as GABA, CACA, or CAMP, in order to treat a coronavirus-induced medical condition in view of the teachings of Duke in view of Bjurstöm and Tang. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor activation leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis.
Regarding claims 60-62 and 67, Duke discloses GABA (Table 1, abstract, and Figure 1).
Regarding claim 63, Duke discloses (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids is controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is advised that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06.
Thus, it is obvious to administer GABA, CACA, or CAMP, taught by Duke in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex Parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected under 35 U.S.C. 103 as being unpatentable over Duke et al. (J. of Neurochem., 75, 2000, 2602-2610) (“Duke”); in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50) (“Bjurstöm”; further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020) (“Tang”); as applied to claims 59-63, 67, 69-71, 74-75, and 77; further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020 – previously cited) (“Sharun”).
The teachings of Duke, Bjurstöm, and Tang are disclosed in the 103 section above and incorporated herein.
While Duke in view of Bjurstöm and Tang does not teach GABA administration together with dexamethasone for the treatment of a coronavirus-related condition, the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected under 35 U.S.C. 103 as being unpatentable over Duke et al. (J. of Neurochem., 75, 2000, 2602-2610) (“Duke”); in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50) (“Bjurstöm”; further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020) (“Tang”); as applied to claims 59-63, 67, 69-71, 74-75, and 77; further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461 – previously cited) (“Solomon”); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107 – previously cited) (“Abdel-Magid”).
The teachings of Duke, Bjurstöm, and Tang are disclosed in the 103 section above and incorporated herein.
While Duke in view of Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators (PAM); and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-62, 67-75, and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Tian et al. (Scientific Reports, 2018, 8: 16555 – previously cited) (“Tian”); in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50 – previously cited) “Bjurstöm”); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020 – previously cited) (“Tang”).
Regarding claim 59, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
While Tian does not teach homotaurine or GABA for the treatment of a coronavirus-induced medical condition, the teachings of Bjurstöm and Tang are relied upon for these disclosures.
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract).
Regarding claim 59, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer GABA inhibitors, such as homotaurine, in order to treat a coronavirus-induced medical condition in view of the teachings of Tian in view of Bjurstöm and Tang. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Tian’s disclosure of homotaurine and GABA as a GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis.
Regarding claims 60-62 and 67-68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 72-73, Tian discloses oral administration of homotaurine (page 2, para. 2, line 3).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer homotaurine or GABA, taught by Tian in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected under 35 U.S.C. 103 as being unpatentable over Tian et al. (Scientific Reports, 2018, 8: 16555) (“Tian”); in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50) “Bjurstöm”); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020) (“Tang”); as applied to claims 59-62, 67-75, and 77; further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020 – previously cited).
The teachings of Tian, Bjurstöm, and Tang are disclosed in the 103 section above and incorporated herein.
While Tian in view of Bjurstöm and Tang does not teach GABA administration together with dexamethasone for the treatment of a coronavirus-related condition, the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Tian’s disclosure of homotaurine and GABA as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected under 35 U.S.C. 103 as being unpatentable over Tian et al. (Scientific Reports, 2018, 8: 16555) (“Tian”); in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50) “Bjurstöm”); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020) (“Tang”); as applied to claims 59-62, 67-75, and 77; further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461 – previously cited) (“Solomon”); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107 – previously cited) (“Abel-Magid”).
The teachings of Tian, Bjurstöm, and Tang are disclosed in the 103 section above and incorporated herein.
While Tian in view of Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the homotaurine for the treatment of the coronavirus-related condition of cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Tian’s disclosure of homotaurine and GABA as a GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
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 59-67, 69-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 7-9 of U.S. Patent No. 6,350,769 B1 (US ‘769); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-67, 69-75, and 77, US ‘769 claims a method of inhibiting an immune response in a patient comprising administration of a GABA agonist (US ‘769 claims 1 and 3).
Further regarding instant claims 60-61, US ‘769 discloses muscimol as a GABA agonist (US ‘769 claim 7).
Further regarding instant claims 64-66, US ‘769 claims coadministration of a GABA potentiator (reading on positive allosteric modulators or PAMs) such as one capable of binding to the benzodiazepine binding site within GABAA (reading on benzodiazepines) (US ‘769 claims 8-9).
Further regarding instant claims 72-73, US ‘769 claims oral, subcutaneous, and transdermal administration of the GABA agonist (US ‘769 claim 2).
While US ‘769 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 62 and 67); (iii) CACA or CAMP as GABA-receptor agonists (claim 63); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Duke, Bjurstöm, and Tang are relied upon for these disclosures.
Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘769’s method of inhibiting an immune response in a patient by administering a GABA-agonist, such as muscimol; Duke’s teachings of GABA, CACA, and CAMP as alternative GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1).
Regarding instant claim 63, Duke teaches (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA, CACA, or CAMP, taught by Duke in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 7-9 of U.S. Patent No. 6,350,769 B1 (US ‘769); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘769, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘769 in view of Duke, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘769’s method of inhibiting an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 59-62, 64-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 7-9 of U.S. Patent No. 6,350,769 B1 (US ‘769); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-62, 64-75, and 77, US ‘769 claims a method of inhibiting an immune response in a patient comprising administration of a GABA agonist (US ‘769 claims 1 and 3).
Further regarding instant claims 60-61, US ‘769 speaks to muscimol as a GABA agonist (US ‘769 claim 7).
Further regarding instant claims 64-66, US ‘769 speaks to coadministration of a GABA potentiator (reading on positive allosteric modulators or PAMs) such as one capable of binding to the benzodiazepine binding site within GABAA (reading on benzodiazepines) (US ‘769 claims 8-9).
Further regarding instant claims 72-73, US ‘769 speaks to oral, subcutaneous, and transdermal administration of the GABA agonist (US ‘769 claim 2).
While US ‘769 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 62 and 67); (iii) homotaurine as a GABA-receptor agonist (claim 68); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vi) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Tian, Bjurstöm, and Tang are relied upon for these disclosures.
Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘769’s method of inhibiting an immune response in a patient by administering a GABA-agonist, such as muscimol; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Tian teaches GABA as a GABAA and GABAC agonist (abstract, lines 9-10).
Regarding instant claim 68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA or homotaurine, taught by Tian in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 7-9 of U.S. Patent No. 6,350,769 B1 (US ‘769); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘769, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘769 in view of Tian, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘769’s method of inhibiting an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 59-67, 69-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 8-11 of U.S. Patent No. 11,992,495 B2 (US ‘495); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610) and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-67, 69-75, and 77, US ‘495 claims a method of reducing an inflammatory immune response by administering a GABAA positive allosteric modulator (PAM) (like alprazolam – reading on a benzodiazepine (claim 66) – see claim interpretation) and GABA (reading on instant claims 64-65) (US ‘495 claim 1). US ‘495 specifically mentions wherein treatment results in downregulation of inflammatory cytokines (US ‘495 claim 2).
While US ‘495 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) CACA or CAMP as GABA-receptor agonists (claim 63); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Duke, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘495’s method of reducing an inflammatory immune response and downregulating cytokine production by administering GABA-receptor agonist, GABA, GABA; Duke’s teachings of GABA, CACA, and CAMP as alternative GABA-receptor agonists; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 60-62 and 67, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1).
Regarding instant claim 63, Duke teaches (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA, taught by US ‘495 to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 8-11 of U.S. Patent No. 11,992,495 B2 (US ‘495); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610) and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘495, Duke, and Tang are disclosed above and incorporated herein.
While US ‘495 in view of Duke and Tang does not teach dexamethasone (claim 76), the teachings of Sharun et al. are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘495’s method of reducing an inflammatory immune response and downregulating cytokine production by administering GABA-receptor agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 59-62, 64-75, and 77 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 8-11 of U.S. Patent No. 11,992,495 B2 (US ‘495); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-62, 64-75, and 77, US ‘495 claims a method of reducing an inflammatory immune response by administering a GABAA positive allosteric modulator (PAM) (like alprazolam – reading on a benzodiazepine (claim 66) – see claim interpretation) and GABA (reading on instant claims 64-65) (US ‘495 claim 1). US ‘495 specifically mentions wherein treatment results in downregulation of inflammatory cytokines (US ‘495 claim 2).
While US ‘495 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) homotaurine as a GABA-receptor agonist (claim 68); (iii) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); (vii) oral administration (claims 72-73); or (viii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Tian and Tang are relied upon for these disclosures.
Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘495’s method of reducing an inflammatory immune response and downregulating cytokine production by administering GABA-receptor agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Tian teaches GABA as a GABAA and GABAC agonist (abstract, lines 9-10).
Regarding instant claim 68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 72-73, Tian discloses oral administration of homotaurine (page 2, para. 2, line 3).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA or homotaurine, taught by US ‘495 in view of Tian to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 8-11 of U.S. Patent No. 11,992,495 B2 (US ‘495); in view of Tian et al. (Scientific Reports, 2018, 8: 16555) and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘495, Tian and Tang are disclosed above and incorporated herein.
While US ‘495 in view of Tian and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘495’s method of reducing an inflammatory immune response and downregulating cytokine production by administering GABA-receptor agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 59-63, 67, 69-71, 74-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of U.S. Patent No. 11,872,200 B2 (US ‘200); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-63, 67, 69-72, 74-75, and 77, US ‘200 speaks to a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘200 claim 7).
While US ‘200 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) CACA or CAMP as GABA-receptor agonists (claim 63); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Duke, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘200’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s teachings of GABA, CACA, and CAMP as alternative GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 60-62 and 67, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1).
Regarding instant claim 63, Duke teaches (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA, CACA, or CAMP, taught by Duke in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of U.S. Patent No. 11,872,200 B2 (US ‘200); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘200, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘200 in view of Duke, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘200’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of U.S. Patent No. 11,872,200 B2 (US ‘200); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘200, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘200 in view of Duke, Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘200’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-62, 67-75, and 77 on the ground of nonstatutory double patenting as being unpatentable over claim 7 of U.S. Patent No. 11,872,200 B2 (US ‘200); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-62, 67-75, and 77, US ‘200 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘200 claim 7).
While US ‘200 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) homotaurine as a GABA-receptor agonist (claim 68); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); (vii) oral administration (claims 72-73); or (viii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Tian, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘200’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Tian teaches GABA as a GABAA and GABAC agonist (abstract, lines 9-10).
Regarding instant claim 68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 72-73, Tian discloses oral administration of homotaurine (page 2, para. 2, line 3).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA or homotaurine, taught by Tian in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of U.S. Patent No. 11,872,200 B2 (US ‘200); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘200, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘200 in view of Tian, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘200’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of U.S. Patent No. 11,872,200 B2 (US ‘200); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘200, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘200 in view of Tian, Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘200’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s disclosure of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-63, 67, 69-71, 74-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 of U.S. Patent No. 10,952,980 B2 (US ‘980); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-63, 67, 69-72, 74-75, and 77, US ‘980 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘980 claims 7-8).
While US ‘980 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) CACA or CAMP as GABA-receptor agonists (claim 63); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Duke, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘980’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering GABA-agonist, GABA; Duke’s teachings of GABA, CACA, and CAMP as alternative GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 60-62 and 67, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1).
Regarding instant claim 63, Duke teaches (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA, CACA, or CAMP, taught by Duke in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 of U.S. Patent No. 10,952,980 B2 (US ‘980); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘980, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘980 in view of Duke, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘980’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 of U.S. Patent No. 10,952,980 B2 (US ‘980); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘980, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘980 in view of Duke, Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid et al. are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘980’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-62, 67-75, and 77 on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 of U.S. Patent No. 10,952,980 B2 (US ‘980); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-62, 67-75, and 77, US ‘980 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘980 claims 7-8).
While US ‘980 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) homotaurine as a GABA-receptor agonist (claim 68); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); (vii) oral administration (claims 72-73); or (viii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Tian, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘980’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Tian teaches GABA as a GABAA and GABAC agonist (abstract, lines 9-10).
Regarding instant claim 68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 72-73, Tian discloses oral administration of homotaurine (page 2, para. 2, line 3).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA or homotaurine, taught by Tian in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 of U.S. Patent No. 10,952,980 B2 (US ‘980); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘980, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘980 in view of Tian, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘980’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8 of U.S. Patent No. 10,952,980 B2 (US ‘980); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘980, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘980 in view of Tian, Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘980’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s disclosure of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-63, 67, 69-71, 74-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 10,434,078 B2 (US ‘078); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-63, 67, 69-72, 74-75, and 77, US ‘078 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘078 claim 4).
While US ‘078 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) CACA or CAMP as GABA-receptor agonists (claim 63); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Duke, Bjurstöm, and Tang are relied upon for these disclosures.
Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘078’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering GABA-agonist, GABA; Duke’s teachings of GABA, CACA, and CAMP as alternative GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 60-62 and 67, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1).
Regarding instant claim 63, Duke teaches (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA, CACA, or CAMP, taught by Duke in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 10,434,078 B2 (US ‘078); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘078, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘078 in view of Duke, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘078’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 10,434,078 B2 (US ‘078); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘078, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘078 in view of Duke, Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘078’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-62, 67-75, and 77 on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 10,434,078 B2 (US ‘078); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-62, 67-75, and 77, US ‘078 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘078 claim 4).
While US ‘078 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) homotaurine as a GABA-receptor agonist (claim 68); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); (vii) oral administration (claims 72-73); or (viii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Tian, Bjurstöm, and Tang are relied upon for these disclosures.
Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘078’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Tian teaches GABA as a GABAA and GABAC agonist (abstract, lines 9-10).
Regarding instant claim 68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 72-73, Tian discloses oral administration of homotaurine (page 2, para. 2, line 3).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA or homotaurine, taught by Tian in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 10,434,078 B2 (US ‘078); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘078, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘078 in view of Tian, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘078’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 10,434,078 B2 (US ‘078); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘078, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘078 in view of Tian, Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘078’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s disclosure of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-63, 67, 69-71, 74-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 9,820,955 B2 (US ‘955); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-63, 67, 69-72, 74-75, and 77, US ‘955 speaks to a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘955 claim 10).
While US ‘955 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) CACA or CAMP as GABA-receptor agonists (claim 63); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Duke, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘955’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering GABA-agonist, GABA; Duke’s teachings of GABA, CACA, and CAMP as alternative GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 60-62 and 67, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1).
Regarding instant claim 63, Duke teaches (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA, CACA, or CAMP, taught by Duke in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 9,820,955 B2 (US ‘955); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘955, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘955 in view of Duke, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘955’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 9,820,955 B2 (US ‘955); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘955, Duke, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘955 in view of Duke, Bjurstöm and Tang does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘955’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-62, 67-75, and 77 on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 9,820,955 B2 (US ‘955); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-62, 67-75, and 77, US ‘955 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘955 claim 10).
While US ‘955 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) homotaurine as a GABA-receptor agonist (claim 68); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); (vii) oral administration (claims 72-73); or (viii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Tian, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘955’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Tian teaches GABA as a GABAA and GABAC agonist (abstract, lines 9-10).
Regarding instant claim 68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 72-73, Tian discloses oral administration of homotaurine (page 2, para. 2, line 3).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA or homotaurine, taught by Tian in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 9,820,955 B2 (US ‘955); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘955, Tian, Bjurstöm, and Tang are disclosed above and incorporated herein.
While US ‘955 in view of Tian, Bjurstöm, and Tang does not teach dexamethasone (claim 76), the teachings of Sharun are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘955’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 9,820,955 B2 (US ‘955); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘955, Tian, Bjurstöm, and Tang et al. are disclosed above and incorporated herein.
While US ‘955 in view of Tian, Bjurstöm and Tang et al. does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid et al. are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘955’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s disclosure of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-63, 67, 69-71, 74-75, and 77 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 9,089,531 B2 (US ‘531); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-63, 67, 69-72, 74-75, and 77, US ‘531 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘531 claim 15).
While US ‘531 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) CACA or CAMP as GABA-receptor agonists (claim 63); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); or (vii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Duke, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘531’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering GABA-agonist, GABA; Duke’s teachings of GABA, CACA, and CAMP as alternative GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 60-62 and 67, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1).
Regarding instant claim 63, Duke teaches (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA, CACA, or CAMP, taught by Duke in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 9,089,531 B2 (US ‘531); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘531, Duke, Bjurstöm, and Tang et al. are disclosed above and incorporated herein.
While US ‘531 in view of Duke, Bjurstöm, and Tang et al. does not teach dexamethasone (claim 76), the teachings of Sharun et al. are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘531’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 9,089,531 B2 (US ‘531); in view of Duke et al. (J. of Neurochem., 75, 2000, 2602-2610); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘531, Duke, Bjurstöm, and Tang et al. are disclosed above and incorporated herein.
While US ‘531 in view of Duke, Bjurstöm and Tang et al. does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid et al. are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘531’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claims 59-62, 67-75, and 77 on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 9,089,531 B2 (US ‘531); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); further in view of Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020).
Regarding instant claims 59-62, 67-75, and 77, US ‘531 claims a method of delaying the onset of an immune response, and/ or slowing the progression of an immune response, and/or reducing the severity of an immune response, and/ or suppressing an immune response in a mammal, comprising administration of GABA (US ‘531 claim 15).
While US ‘531 does not teach: (i) the treatment of a coronavirus-induced medical condition (all instant claims); (ii) GABA as a GABA-receptor agonist (claims 60-62 and 67); (iii) homotaurine as a GABA-receptor agonist (claim 68); (iv) SARS-CoV or SARS-CoV-2 (claims 69-70); (v) wherein the coronavirus-induced medical condition results in death, fever, or illness (claim 71); (vii) oral administration (claims 72-73); or (viii) coadministration of an anti-inflammatory compound, such as a corticosteroid (claims 74-75 and 77); the teachings of Tian, Bjurstöm, and Tang et al. are relied upon for these disclosures.
Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9) and also discloses GABA as a GABA-receptor agonist (abstract, lines 9-10).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract). Tang further describes cytokine storm as an unregulated immune response by the infected host (page 1708, Introduction, para. 2, lines 3-5).
Regarding instant claims 59, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a GABA-agonist for the treatment of a coronavirus-induced condition, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘531’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high concentrations of pro-inflammatory cytokines, and that cytokine storm is an unregulated immune response by the infected host.
Regarding instant claims 62 and 67, Tian teaches GABA as a GABAA and GABAC agonist (abstract, lines 9-10).
Regarding instant claim 68, Tian teaches homotaurine as a GABAA receptor agonist (title and abstract, lines 8-9).
Regarding claims 69-70, Tang discloses SARS-CoV-2 (abstract).
Regarding claim 71, Tang discloses COVID-19-related cytokine storm may result in death, as evidenced by postmortem examination of lung tissues of patients (abstract, lines 6-9).
Regarding claims 72-73, Tian discloses oral administration of homotaurine (page 2, para. 2, line 3).
Regarding claims 74-75, Tang teaches corticosteroid (glucocorticoid) therapy is widely used among critically ill patients with coronavirus infections as it proffers inhibitory actions of the transcription and action of various cytokines (page 5, col. 1, last para.). Tang suggests that treatment with corticosteroids in controversial for regular COVID-19 cases and suggests more success with critical cases (page 5, col. 2, lines 1-2 and 10 to end of para.) such as cases exhibiting the coronavirus-related condition of cytokine storm, as the instant claims require.
Applicant is reminded that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to administer GABA or homotaurine, taught by Tian in view of Bjurstöm to inhibit cytokine production, with a corticosteroid (such as glucocorticoid), taught by Tang to act as a cytokine inhibitor effective for severe cases of coronavirus-related cytokine storm.
Regarding claim 77, with respect to the order of steps, Applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Claim 76 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 9,089,531 B2 (US ‘531); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Sharun et al. (International Journal of Surgery, 82, 2020, 179–181 – Published September 4th, 2020).
The teachings of US ‘531, Tian, Bjurstöm, and Tang et al. are disclosed above and incorporated herein.
While US ‘531 in view of Tian, Bjurstöm, and Tang et al. does not teach dexamethasone (claim 76), the teachings of Sharun et al. are relied upon for these disclosures.
Sharun discloses dexamethasone as a corticosteroid anti-inflammatory with the ability to decrease gene transcription of several pro-inflammatory cytokines (page 179, col. 1, para. 2, lines 6-12). Sharun discloses preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19 (title; page 179, col. 2, last para. to page 180, col. 1, para. 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer a GABA-receptor agonist with an anti-inflammatory corticosteroid, such as dexamethasone for the treatment of coronavirus-mediated conditions, such as cytokine storm. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘531’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s teachings of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; and Sharun specific disclosure of preliminary evidence that dexamethasone works to combat cytokine storm in COVID-19.
Applicant is reminded that it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.
Applicant is reminded that the arguments of counsel cannot take the place of evidence in the record.
Claims 64-66 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 9,089,531 B2 (US ‘531); in view of Tian et al. (Scientific Reports, 2018, 8: 16555); further in view of Bjurstöm et al. (Journal of Neuroimmunology, 205, 2008, 44–50); and Tang et al. (Frontiers in Immunology, 2020, 11, Article No. 1708 – Pub. Date: July 10th, 2020); as applied to claim 59, further in view of Solomon et al. (European Journal of Medicinal Chemistry, 171, 2019, 434e461); and Abdel-Magid et al. (ACS Med. Chem. Lett., 2015, 6, 104–107).
The teachings of US ‘531, Tian, Bjurstöm, and Tang et al. are disclosed above and incorporated herein.
While US ‘531 in view of Tian, Bjurstöm and Tang et al. does not teach coadministration of positive allosteric modulators (PAMs) (claims 64-66); the teachings of Solomon and Abdel-Magid et al. are relied upon for these disclosures.
Solomon discloses GABA allosteric modulators benzodiazepine and non-benzodiazepine ligands (abstract, lines 13-15).
Abdel-Magid teaches that a new emerging approach to drug design is based on secondary binding site effects, where a small molecule designed to bind into a secondary (allosteric) site modifies the conformation of the primary binding site, thus increasing activity (for PAM) (page 104, para. 2-3, and point 1).
Therefore, regarding claims 64 and 66, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer a PAM together with the GABA agonist treatment for a coronavirus-related condition. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘531’s method of slowing, reducing, and/or suppressing an immune response in a patient by administering a GABA-agonist; Tian’s disclosure of GABA and homotaurine as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis; Solomon’s disclosure of different GABA positive allosteric modulators; and Abdel-Magid’s teachings that administration of a PAM with a drug increases the desired effect of the drug, thus maximizing the efficacy of treatment and ameliorating the coronavirus-related cytokine storm.
Regarding claim 65, with respect to the order of steps, applicant is reminded that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Therefore, the claimed order of steps is an obvious variant of the steps of the cited prior art.
Response to Arguments
Claims/ Claim Objections
Claim amendments are acknowledged. No new matter has been introduced.
Applicant’s arguments, see page 9, filed 02/09/2026, with respect to claim objections have been fully considered and are persuasive. The objections of the claims have been withdrawn.
Claim Rejections - 35 USC § 112(b)
Applicant’s arguments, see page 10, filed 02/09/2026, with respect to 35 USC § 112(b) rejections have been fully considered and are persuasive. The 35 USC § 112(b) rejections of the claims have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 02/09/2026 have been fully considered but they are not persuasive.
Applicant argues it is essential that cited art be perceived before the time of the invention and without knowledge of the invention. Applicant argues that Duke, Bjurstöm, and Tang fail to disclose or suggest all elements of the claims – however, applicant fails to specifically point out the alleged deficiencies in the cited art. Applicant cites Tobiaiqy, Li, Andrews, Veerdonk, and Toussi to say that, since these references do not disclose GABA-receptor agonists to treat coronavirus-induced medical conditions, then the instant claims are not obvious – however, none of these references were relied upon for the rejections of record, and furthermore, citing five specific reports does not negate or discredit the obviousness arguments presented herein. Applicant further states that Examiner utilized hindsight reasoning to reconstruct the instant invention, since there is no evidence of why one skilled in the art would have selected Duke, Bjurstöm, and Tang without knowledge of the instant invention. Applicant further states rejections are improper “because one of ordinary skill in the art empirically did not simply select and modify [the cited art]”.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See 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), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, as stated above, Duke teaches GABA as a GABAA and GABAC agonist (Table 1, entry 1), (+)-CAMP as a potent GABAC agonist (abstract, lines 6-7) and discloses that CACA selectively activates GABAC receptors (page 2603, col.1, last para. line 1).
Bjurstöm teaches a model via which GABA receptor inhibition leads to inhibition of cytokine production (Figure 3 and page 49, col. 1, section 4.1). Bjurstöm proposes that activation of GABA (Cl-) channels decreases entry of calcium into the cell, reducing Ca2+ dependent processes involved in lymphocyte activation, such as cytokine production.
Tang teaches SARS-CoV-2, the pathogen that causes coronavirus disease ’19 (COVID-19), in severely ill patients showed high concentrations of pro-inflammatory cytokines compared to those who were moderately ill. Tang discloses that high levels of cytokines was indicative of poor prognosis, and that excessive infiltration of pro-inflammatory cells, such as macrophages and T-helper 17 cells, was found in lung tissues of COVID-19 patients after postmortem examination. Tang further teaches that the cytokine storm may contribute to the mortality of COVID-19 (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to administer GABA inhibitors, such as GABA, CACA, or CAMP, in order to treat a coronavirus-induced medical condition in view of the teachings of Duke in view of Bjurstöm and Tang. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Duke’s disclosure of GABA, CACA, or CAMP as GABA-receptor agonists; Bjurstöm’s teachings that GABA receptor inhibition leads to inhibition of cytokine production; and Tang’s teachings that severely ill COVID-19 patients showed high levels of pro-inflammatory cytokines, and that high levels of cytokines was indicative of poor prognosis.
In response to applicant’s arguments that it is essential that cited art be perceived before the time of the invention and without knowledge of the invention, all of the cited art of record was made public before the effective filing date of the instant application.
In response to Applicant’s arguments that Tobiaiqy, Li, Andrews, Veerdonk, and Toussi do not disclose GABA-receptor agonists for the treatment of COVID-19; Applicant is advised that these references were not relied upon for the rejections of record. Furthermore, the allegation that these specific references did not consider the claimed treatment form of for COVID-19 is not empirical proof that the instant invention is not obvious – see 103 rejections of record.
In order for arguments to be persuasive, Applicant would need to show unexpected results, for example, by demonstrating exceptional success in treatment or amelioration of coronavirus-induced medical conditions after administering a GABA-receptor agonist, as claimed, compared to other known treatment methods.
Double Patenting
Applicant's arguments filed 02/09/2026 have been fully considered but they are not persuasive.
Applicant argues non-statutory double patenting rejections of record use two to five reference combinations, and alleges that, had applicant’s invention been obvious, then Applicant’s claimed subject matter would have been employed to combat COVID-19, once again citing “empirical evidence, such as Tobiaiqy, Li, Andrews, Veerdonk, and Toussi”. Applicant asserts the examiner used hindsight reasoning, and that combinations of up to six publications is not permissible.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, Applicant is reminded that it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper.
In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991). Furthermore, Applicant fails to specifically point out the deficiencies in the obviousness argument of record.
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
Claims stand rejected over NSDP rejections of record. This action is final.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627