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 statement (IDS) submitted on 09/04/2025 was filed after the mailing date of the non-final on 08/06/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of the Claims
Claims 35-38, 40-42, 44-48, and 50-54 are pending in this application. Claims 1-34, 39, 43, and 49 have been cancelled by applicant.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 35-38, 40-41, and 54 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 35 is unclear because it relates to “a method of treating … comprising cysteamine or cystamine … wherein the method comprises inhibiting the activity of glycine decarboxylase”. Either the term “administering” is missing, as in “a method of treating … comprising administering cysteamine or cystamine” or the steps involved with “inhibiting” are unclear.
Claims 36-38, 40-41, and 54 are indefinite for depending upon the limitations of claim 35.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 35-38 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited) (“Thoene”).
Regarding claim 35, Thoene discloses a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4).
Applicant is advised that a recitation of the intended use of the claimed invention, such as the “treatment by inhibiting the activity of glycine decarboxylase” in the instant application, must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Note: MPEP 2111.02.
In the present case, Thoene discloses treatment of the same class of viral infection by administering the claimed compound. Therefore, the recitation of the mode of action of Thoene’s method of treatment does not render the instant claims patentable. Furthermore, Applicant is advised that products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Regarding claim 36, Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Regarding claims 37-38, Thoene speaks to a method of treating infections caused by coronavirus (Thoene claim 3).
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 40-41 and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited) (“Theone”); as applied to claims 35-38; in view of Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439) (“Karim”); further in view of Alves et al. (Nutrients, 2019, 11, 1356, 28 pages) (“Alves”); and Milind et al. (Wayne State University Dissertations, 2020, URL:https://digitalcommons.wayne.edu/oa_dissertations/2491> - Pub. Date: January 2020) (“Milind”).
The teachings of Thoene are disclosed above and incorporated herein.
Thoene further discloses methods for treating subjects diagnosed with, or susceptible to, viral infections (reading on prophylactic treatment) (page 4, lines 9-10 and 13), including herpesviruses and hepatoviruses (i.e., hepatitis; claim 3 of Thoene).
While Thoene does not specifically tech: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L or a subject with elevated glycine decarboxylase activity (GLDC) (claims 40 and 54); or (ii) the prophylactic treatment of viral infections (claim 41); the teachings of Karim and Alves are relied upon for these disclosures.
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Milind describes how upregulated GLDC activity in rodent models leads to metabolic stress; obesity and diabetes (page vi, last para.; and Chapter 2).
Regarding claims 40-41 and 54, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L and with elevated GLDC activity; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L or elevated GLDC activity. One of ordinary skill would have been motivated to do so in view of Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L; and Milind teaches that elevated GLDC activity leads to obesity. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly in obese patients with reduced levels of glycine and elevated levels of GLDC activity, as taught by Alves and Milind, who have a higher risk of T2DM).
Claims 42 and 43-47 are rejected under 35 U.S.C. 103 as being unpatentable over Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited) (“Theone”); in view of Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439) (“Karim”); further in view of Alves et al. (Nutrients, 2019, 11, 1356, 28 pages) (“Alves”).
Regarding claim 42, Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4).
While Thoene doesn’t specifically teach: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L (claim 42); or (ii) the prophylactic treatment of viral infections (claim 46); the teachings of Karim and Alves are relied upon for these disclosures.
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Regarding claims 42 and 46, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L. One of ordinary skill would have been motivated to do so in view of Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly obese patients with reduced levels of glycine, as taught by Alves, who have a higher risk of T2DM).
Regarding claim 44, Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Regarding claims 45 and 47, Thoene speaks to a method of treating infections caused by coronavirus (Thoene claim 3).
Claims 48 and 50-53 are rejected under 35 U.S.C. 103 as being unpatentable over Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited) (“Thoene”); in view of Buiser et al. (Obtained from nursingcenter.com [retrieved on July 30th, 2025] <URL: https://www.nursingcenter.com/blogs-plus/blogs/blogs-post?identifier=Is-COVID-19-Fueled-by-a-Cytokine-Storm#/post/Is-COVID-19-Fueled-by-a-Cytokine-Storm> - Published on April 8th, 2020 – previously cited) (“Buiser”); further in view of Ferrari et al. (Cell Death and Disease, 2017, 8, e2544, 11 pages – previously cited) (“Ferrari”).
Regarding claims 48, Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be coronavirus, and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene specifically mentions treatment of pneumonia with their method – reading on the instant claim (Thoene’s claim 3, line 2).
While Thoene does not specifically tech the treatment of hyperinflammation in their subject with pneumonia, the teachings of Buiser and Ferrari are relied upon for these disclosures.
Buiser teaches SARS-CoV-2 (a coronavirus) infections lead to cytokine release syndrome (CRS), also known as cytokine storm. CRS has been described as acute inflammatory syndrome (page 2, para. 2, lines 1-3). Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8).
Ferrari teaches cysteamine decreases the production of inflammatory cytokines (page 5, col. 2, para. 2).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of cytokine release syndrome (CRS), which is a form of hyperinflammation caused by a coronavirus infection, such as pneumonia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Thoene’s teachings that cysteamine is effective for the treatment of coronavirus infections, including pneumonia; Buiser’s teachings that SARS-CoV-2 (a coronavirus) leads to cytokine release syndrome and hyperinflammation; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines, thus treating the hyperinflammation whilst treating the coronavirus inflection, such as pneumonia.
Regarding claim 50-51, Thoene teaches the treatment of viral infections, including pneumonia (Thoene claims 2-3) and Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of inflammation caused by pneumonia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Thoene’s teachings of the treatment of viral infections, including pneumonia, with cysteamine; Buiser’s teachings that a cytokine inhibitor was effective to treat COVID-19 pneumonia; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines.
Regarding claim 52, Thoene teaches the treatment of influenza with cysteamine, and that symptoms include acute respiratory distress (page 3, lines 1-4). Buiser discloses the symptoms of a COVID-19 infection include acute respiratory distress syndrome (ARDS) (page 3, Laboratory Findings, lines 10-11).
Regarding claim 53, Thoene discloses their cysteamine treatment can be administered via injection or orally (page 9, last 2 lines).
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 48 and 50-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3 and 14-15 of U.S. Patent No. 9,339,525 B2 (US ‘525) – From IDS, in view of Endeman et al. (Eur. Respir. J., 2011; 37: 1431–1438 – previously cited); further in view of Ferrari et al. (Cell Death and Disease, 2017, 8, e2544, 11 pages – previously cited).
Regarding instant claims 48 and 50-51, US ‘525 speaks to a method of treatment for a bacterial respiratory infection (reading on bacterial pneumonia) by administering a composition comprising cysteamine (US ‘525 claims 3 and 14-15).
While US ‘525 does not specifically teach the treatment of hyperinflammation, the teachings of Endeman and Ferrari are relied upon for these disclosures.
Endeman discloses higher levels of inflammatory cytokines in patients with bacterial pneumonia (abstract) – see claim interpretation section for interpretation of hyperinflammation. Endeman teaches pneumococcal pneumonia is rapid and sever, with patients coming to the hospital shortly after or at the peak of a cytokine storm (page 1436, col. 2, last para.).
Ferrari teaches cysteamine decreases the production of inflammatory cytokines (page 5, col. 2, para. 2).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘525’s cysteamine composition for the treatment of hyperinflammation that may be due to a bacterial respiratory infection, such as bacterial pneumonia. One of ordinary skill would have been motivated to do so in view of US ‘525’s teachings that cysteamine is effective for the treatment of bacterial respiratory infections; Endeman’s teachings that bacterial pneumonia may lead to a cytokine storm, resulting in hyperinflammation in a subject; and Ferrari’s teachings that cysteamine can decrease the production of inflammatory cytokines, resulting in amelioration of hyperinflammation.
Claims 48 and 50-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-5 of U.S. Patent No. 9,364,491 B2 (US ‘491) – From IDS, in view of Sadikot et al. (Am. J. Respir. Crit. Care Med., 2005, 171, 1209-1223 – previously cited); further in view of Ferrari et al. (Cell Death and Disease, 2017, 8, e2544, 11 pages – previously cited).
Regarding instant claims 48 and 50-51, US ‘491 speaks to a method of treatment for a bacterial respiratory infection (reading on bacterial pneumonia) by administering a composition comprising cysteamine (US ‘491 claims 1 and 3-5).
While US ‘491 does not specifically teach the treatment of hyperinflammation, the teachings of Sadikot and Ferrai are relied upon for these disclosures.
Sadikot discloses P. aeruginosa colonization of the respiratory tract is often followed by acute pneumonia, sepsis, and death (page 1209, col. 2, para. 2, lines 5-7). Sadikot teaches IL-1 and IL-18 activity impairs bacterial clearance in P. aeruginosa lung infections (page 1217, col. 1, para. 3, last 3 lines). Sadikot’s teachings suggest that inflammatory cytokine activity hinders a subject’s ability to rid themselves of the bacterial infection, leading to sepsis (reading on hyperinflammation – see claim interpretation) and death.
Ferrari teaches cysteamine decreases the production of inflammatory cytokines (page 5, col. 2, para. 2).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘491’s cysteamine composition for the treatment of hyperinflammation that may be due to a bacterial respiratory infection, such as bacterial pneumonia caused by P. aeruginosa. One of ordinary skill would have been motivated to do so in view of US ‘491’s teachings that cysteamine is effective for the treatment of P. aeruginosa respiratory infections; Sadikot’s suggestion that inflammatory cytokine activity hinders a subject’s ability to rid themselves of the bacterial infection, leading to sepsis, and hyperinflammation; and Ferrari’s teachings that cysteamine can decrease the production of inflammatory cytokines, resulting in amelioration of the bacterial infection and hyperinflammation.
Claims 35-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16-18 of U.S. Patent No. 10,905,660 B2 (US ‘660); in view of Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited).
Regarding instant claims 35-38, US ‘660 speaks to a method of treatment for lung disease (reading on viral and bacterial respiratory infections) comprising administration of a pharmaceutical composition comprising cysteamine (US ‘660 claims 1 and 16-17).
While US ‘660 does not specifically teach: (i) RNA virus infections (instant claims 36-38), the teachings of Thoene are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘660’s cysteamine formulation for the treatment of RNA virus infections in view of Thoene. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘660’s disclosure of a cysteamine formulation for the treatment of respiratory diseases, such as pneumonia; and Thoene’s disclosure that cysteamine is effective for the treatment of RNA virus infections, including respiratory infections like coronavirus.
Applicant is advised that a recitation of the intended use of the claimed invention, such as the “treatment by inhibiting the activity of glycine decarboxylase” in the instant application, must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Furthermore, Applicant is reminded that products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Claims 40-41 and 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16-18 of U.S. Patent No. 10,905,660 B2 (US ‘660); in view of Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited); and Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439 – previously cited); as applied to claims 35-38; further in view of Alves et al. (Nutrients 2019, 11, 1356, 28 pages) (“Alves”); and Milind et al. (Wayne State University Dissertations, 2020, <URL:https://digitalcommons.wayne.edu/oa_dissertations/2491> - Pub. Date: January 2020) (“Milind”).
The teachings of US ‘660 and Thoene are disclosed above and incorporated herein.
Thoene further discloses methods for treating subjects diagnosed with, or susceptible to, viral infections (reading on prophylactic treatment) (page 4, lines 9-10 and 13), including herpesviruses and hepatoviruses (i.e., hepatitis; claim 3 of Thoene).
While US ‘660 in view of Thoene does not specifically teach: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L or a subject with elevated glycine decarboxylase activity (GLDC) (claims 40 and 54); or (ii) the prophylactic treatment of viral infections (claim 41); the teachings of Karim, Alves, and Milind are relied upon for these disclosures.
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Milind describes how upregulated GLDC activity in rodent models leads to metabolic stress; obesity and diabetes (page vi, last para.; and Chapter 2).
Regarding claims 40-41 and 54, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L and with elevated GLDC activity; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L or elevated GLDC activity. One of ordinary skill would have been motivated to do so in view of US ‘660’s method of treating lung disease by administering cysteamine; Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L; and Milind teaches that elevated GLDC activity leads to obesity. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly in obese patients with reduced levels of glycine and elevated levels of GLDC activity, as taught by Alves and Milind, who have a higher risk of T2DM).
Claims 42 and 44-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16-18 of U.S. Patent No. 10,905,660 B2 (US ‘660); in view of Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited); and Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439); further in view of Alves et al. (Nutrients 2019, 11, 1356, 28 pages) (“Alves”).
Regarding instant claims 42 and 44-47, US ‘660 speaks to a method of treatment for lung disease (reading on viral and bacterial respiratory infections) comprising administration of a pharmaceutical composition comprising cysteamine (US ‘660 claims 1 and 16-17).
While US ‘660 does not specifically teach: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L (claim 42); (ii) RNA virus infections (instant claims 44-46); or (iii) the prophylactic treatment of viral infections (claim 46); the teachings of Thoene and Karim et al. are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Regarding claims 42 and 44-46, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L. One of ordinary skill would have been motivated to do so in view of US ‘660’s disclosure of a method of treating lung disease comprising administration of cysteamine; Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly obese patients with reduced levels of glycine, as taught by Alves, who have a higher risk of T2DM).
Claims 48 and 50-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 16-18 of U.S. Patent No. 10,905,660 B2 (US ‘660); in view of Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited); Buiser et al. (Obtained from nursingcenter.com [retrieved on July 30th, 2025] <URL: https://www.nursingcenter.com/blogs-plus/blogs/blogs-post?identifier=Is-COVID-19-Fueled-by-a-Cytokine-Storm#/post/Is-COVID-19-Fueled-by-a-Cytokine-Storm> - Published on April 8th, 2020 – previously cited); and Ferrari et al. (Cell Death and Disease, 2017, 8, e2544, 11 pages – previously cited).
Regarding instant claims 48 and 50-53, US ‘660 speaks to a method of treatment for lung disease (reading on viral and bacterial respiratory infections) comprising administration of a pharmaceutical composition comprising cysteamine (US ‘660 claims 1 and 16-17). Further regarding instant claim 53, US ‘660 discloses their cysteamine formulation as a dry powder (US ‘660 claim 7).
While US ‘660 does not specifically teach: (i) the treatment of hyperinflammation; (ii) or IV or oral administration of the cysteamine composition; the teachings of Thoene, Buiser, and Ferrari et al. are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3). Thoene discloses their cysteamine treatment can be administered via injection or orally (page 9, last 2 lines).
Buiser teaches SARS-CoV-2 (a coronavirus) infections lead to cytokine release syndrome (CRS), also known as cytokine storm. CRS has been described as acute inflammatory syndrome (page 2, para. 2, lines 1-3). Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8).
Ferrari teaches cysteamine decreases the production of inflammatory cytokines (page 5, col. 2, para. 2).
Regarding instant claims 48, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘660’s cysteamine formulation for the treatment of cytokine release syndrome (CRS), which is a form of hyperinflammation caused by a coronavirus infection. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘660’s disclosure of a cysteamine formulation Thoene’s teachings that cysteamine is effective for the treatment of coronavirus infections; Buiser’s teachings that SARS-CoV-2 (a coronavirus) leads to cytokine release syndrome and hyperinflammation; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines, thus treating the hyperinflammation whilst treating the coronavirus inflection.
Regarding claim 50-51, Thoene teaches the treatment of viral infections, including pneumonia with cysteamine (Thoene claims 2-3) and Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘660’s cysteamine formulation for the treatment of inflammation caused by pneumonia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘660’s disclosure of a cysteamine formulation; Thoene’s teachings of the treatment of viral infections, including pneumonia, with cysteamine; Buiser’s teachings that a cytokine inhibitor was effective to treat COVID-19 pneumonia; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines.
Regarding claim 52, Thoene teaches the treatment of influenza with cysteamine, and that symptoms include acute respiratory distress (page 3, lines 1-4). Buiser discloses the symptoms of a COVID-19 infection include acute respiratory distress syndrome (ARDS) (page 3, Laboratory Findings, lines 10-11).
Regarding claim 53, Thoene discloses their cysteamine treatment can be administered via injection or orally (page 9, last 2 lines).
Claims 35-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,369,568 B2 (US ‘568); in view of Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited).
Regarding instant claims 35-38, US ‘568 speaks to a method of treatment for lung disease (reading on viral and bacterial respiratory infections) comprising administration of a pharmaceutical composition comprising cysteamine (US ‘660 claims 1-16).
While US ‘568 does not specifically teach: (i) RNA virus infections (instant claims 36-38), the teachings of Thoene are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘568’s cysteamine formulation for the treatment of RNA virus infections in view of Thoene. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘568’s disclosure of a cysteamine formulation for the treatment of respiratory diseases, such as pneumonia; and Thoene’s disclosure that cysteamine is effective for the treatment of RNA virus infections, including respiratory infections like coronavirus.
Applicant is reminded that a recitation of the intended use of the claimed invention, such as the “treatment by inhibiting the activity of glycine decarboxylase” in the instant application, must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Furthermore, Applicant is reminded that products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Claims 40-41 and 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,369,568 B2 (US ‘568) – From IDS; in view of Thoene et al. (WO 2010/138419 A2 – From IDS); and Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439 – previously cited); as applied to claims 35-38; further in view of Alves et al. (Nutrients 2019, 11, 1356, 28 pages) (“Alves”); and Milind et al. (Wayne State University Dissertations, 2020, URL:https://digitalcommons.wayne.edu/oa_dissertations/2491> - Pub. Date: January 2020) (“Milind”).
The teachings of US ‘568 and Thoene are disclosed above and incorporated herein.
Thoene further discloses methods for treating subjects diagnosed with, or susceptible to, viral infections (reading on prophylactic treatment) (page 4, lines 9-10 and 13), including herpesviruses and hepatoviruses (i.e., hepatitis; claim 3 of Thoene).
While US ‘568 in view of Thoene does not specifically teach: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L or a subject with elevated glycine decarboxylase activity (GLDC) (claims 40 and 54); or (ii) the prophylactic treatment of viral infections (claim 41); the teachings of Karim, Alves, and Milind are relied upon for these disclosures.
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Milind describes how upregulated GLDC activity in rodent models leads to metabolic stress; obesity and diabetes (page vi, last para.; and Chapter 2).
Regarding claims 40-41 and 54, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L and with elevated GLDC activity; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L or elevated GLDC activity. One of ordinary skill would have been motivated to do so in view of US ‘568’s method of treating lung disease by administering cysteamine; Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L; and Milind teaches that elevated GLDC activity leads to obesity. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly in obese patients with reduced levels of glycine and elevated levels of GLDC activity, as taught by Alves and Milind, who have a higher risk of T2DM).
Claims 42 and 44-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,369,568 B2 (US ‘568); in view of Thoene et al. (WO 2010/138419 A2 – From IDS); and Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439); further in view of Alves et al. (Nutrients 2019, 11, 1356, 28 pages) (“Alves”).
Regarding instant claims 42 and 44-47, US ‘568 speaks to a method of treatment for lung disease (reading on viral and bacterial respiratory infections) comprising administration of a pharmaceutical composition comprising cysteamine (US ‘568 claims 1-16).
While US ‘568 does not specifically teach: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L (claim 42); (ii) RNA virus infections (instant claims 44-46); or (iii) the prophylactic treatment of viral infections (claim 46); the teachings of Thoene and Karim et al. are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Regarding claims 42 and 44-46, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L. One of ordinary skill would have been motivated to do so in view of US ‘568’s disclosure of a method of treating lung disease comprising administration of cysteamine; Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly obese patients with reduced levels of glycine, as taught by Alves, who have a higher risk of T2DM).
Claims 48 and 50-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,369,568 B2 (US ‘568) – From IDS; in view of Thoene et al. (WO 2010/138419 A2 – From IDS); Buiser et al. (Obtained from nursingcenter.com [retrieved on July 30th, 2025] <URL: https://www.nursingcenter.com/blogs-plus/blogs/blogs-post?identifier=Is-COVID-19-Fueled-by-a-Cytokine-Storm#/post/Is-COVID-19-Fueled-by-a-Cytokine-Storm> - Published on April 8th, 2020); and Ferrari et al. (Cell Death and Disease, 2017, 8, e2544, 11 pages).
Regarding instant claims 48 and 50-53, US ‘568 speaks to a method of treatment for lung disease (reading on viral and bacterial respiratory infections) comprising administration of a pharmaceutical composition comprising cysteamine (US ‘568 claims 1-16). Further regarding instant claim 53, US ‘660 discloses their cysteamine formulation as a dry powder (US ‘568 claim 16).
While US ‘568 does not specifically teach: (i) the treatment of hyperinflammation; (ii) or IV or oral administration of the cysteamine composition; the teachings of Thoene, Buiser, and Ferrari et al. are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3). Thoene discloses their cysteamine treatment can be administered via injection or orally (page 9, last 2 lines).
Buiser teaches SARS-CoV-2 (a coronavirus) infections lead to cytokine release syndrome (CRS), also known as cytokine storm. CRS has been described as acute inflammatory syndrome (page 2, para. 2, lines 1-3). Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8).
Ferrari teaches cysteamine decreases the production of inflammatory cytokines (page 5, col. 2, para. 2).
Regarding instant claim 48, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘568’s cysteamine formulation for the treatment of cytokine release syndrome (CRS), which is a form of hyperinflammation caused by a coronavirus infection. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘568’s disclosure of a cysteamine formulation Thoene’s teachings that cysteamine is effective for the treatment of coronavirus infections; Buiser’s teachings that SARS-CoV-2 (a coronavirus) leads to cytokine release syndrome and hyperinflammation; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines, thus treating the hyperinflammation whilst treating the coronavirus inflection.
Regarding claim 50-51, Thoene teaches the treatment of viral infections, including pneumonia with cysteamine (Thoene claims 2-3) and Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘568’s cysteamine formulation for the treatment of inflammation caused by pneumonia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of US ‘568’s disclosure of a cysteamine formulation; Thoene’s teachings of the treatment of viral infections, including pneumonia, with cysteamine; Buiser’s teachings that a cytokine inhibitor was effective to treat COVID-19 pneumonia; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines.
Regarding claim 52, Thoene teaches the treatment of influenza with cysteamine, and that symptoms include acute respiratory distress (page 3, lines 1-4). Buiser discloses the symptoms of a COVID-19 infection include acute respiratory distress syndrome (ARDS) (page 3, Laboratory Findings, lines 10-11).
Regarding claim 53, Thoene discloses their cysteamine treatment can be administered via injection or orally (page 9, last 2 lines).
Claims 35-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 9-15 of copending Application No. 17/286,282 (Copending ‘282); in view of Thoene et al. (WO 2010/138419 A2 – From IDS – previously cited).
Regarding instant claims 35-38, Copending ‘282 claims a method of treatment for pulmonary cystic fibrosis comprising administration of a pharmaceutical composition comprising cysteamine (Copending ‘282 claim 1).
While Copending ‘282 does not specifically teach: (i) treatment of RNA virus infections (instant claims 36-38), the teachings of Thoene are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘282’s cysteamine formulation for the treatment of RNA virus infections in view of Thoene. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘282’s disclosure of a cysteamine formulation for the treatment of respiratory diseases, such as pneumonia; and Thoene’s disclosure that cysteamine is effective for the treatment of RNA virus infections, including respiratory infections like coronavirus.
Applicant is reminded that a recitation of the intended use of the claimed invention, such as the “treatment by inhibiting the activity of glycine decarboxylase” in the instant application, must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Furthermore, Applicant is reminded that products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
This is a provisional nonstatutory double patenting rejection.
Claims 40-41 and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 9-15 of copending Application No. 17/286,282 (Copending ‘282); in view of Thoene et al. (WO 2010/138419 A2 – From IDS); and Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439 – previously cited); as applied to claims 35-38; further in view of Alves et al. (Nutrients 2019, 11, 1356, 28 pages) (“Alves”); and Milind et al. (Wayne State University Dissertations, 2020, <URL:https://digitalcommons.wayne.edu/oa_dissertations/2491> - Pub. Date: January 2020) (“Milind”).
The teachings of Copending ‘282 and Thoene are disclosed above and incorporated herein.
Thoene further discloses methods for treating subjects diagnosed with, or susceptible to, viral infections (reading on prophylactic treatment) (page 4, lines 9-10 and 13), including herpesviruses and hepatoviruses (i.e., hepatitis; claim 3 of Thoene).
While Copending ‘282 in view of Thoene does not specifically teach: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L or a subject with elevated glycine decarboxylase activity (GLDC) (claims 40 and 54); or (ii) the prophylactic treatment of viral infections (claim 41); the teachings of Karim, Alves, and Milind are relied upon for these disclosures.
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Milind describes how upregulated GLDC activity in rodent models leads to metabolic stress; obesity and diabetes (page vi, last para.; and Chapter 2).
Regarding claims 40-41 and 54, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L and with elevated GLDC activity; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L or elevated GLDC activity. One of ordinary skill would have been motivated to do so in view of Copending ‘282’s method of treating lung disease by administering cysteamine; Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L; and Milind teaches that elevated GLDC activity leads to obesity. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly in obese patients with reduced levels of glycine and elevated levels of GLDC activity, as taught by Alves and Milind, who have a higher risk of T2DM).
This is a provisional nonstatutory double patenting rejection.
Claims 42 and 44-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 9-15 of copending Application No. 17/286,282 (Copending ‘282); in view of Thoene et al. (WO 2010/138419 A2 – From IDS); and Karim et al. (CNS & Neurological Disorders - Drug Targets, 2014, 13, 429-439); further in view of Alves et al. (Nutrients 2019, 11, 1356, 28 pages) (“Alves”).
Regarding instant claims 42 and 44-47, Copending ‘282 claims a method of treatment for pulmonary cystic fibrosis comprising administration of a pharmaceutical composition comprising cysteamine (Copending ‘282 claim 1).
While Copending ‘282 does not specifically teach: (i) a method of treating a viral infection in patients who have plasma concentrations lower than or equal to 300 µmol/L (claim 42); (ii) RNA virus infections (instant claims 44-46); or (iii) the prophylactic treatment of viral infections (claim 46); the teachings of Thoene and Karim are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3).
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Regarding claims 42 and 44-46, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L. One of ordinary skill would have been motivated to do so in view of Copending ‘282’s disclosure of a method of treating lung disease comprising administration of cysteamine; Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly obese patients with reduced levels of glycine, as taught by Alves, who have a higher risk of T2DM).
This is a provisional nonstatutory double patenting rejection.
Claims 48 and 50-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 9-15 of copending Application No. 17/286,282 (Copending ‘282); in view of Thoene et al. (WO 2010/138419 A2 – From IDS); Buiser et al. (Obtained from nursingcenter.com [retrieved on July 30th, 2025] <URL: https://www.nursingcenter.com/blogs-plus/blogs/blogs-post?identifier=Is-COVID-19-Fueled-by-a-Cytokine-Storm#/post/Is-COVID-19-Fueled-by-a-Cytokine-Storm> - Published on April 8th, 2020); and Ferrari et al. (Cell Death and Disease, 2017, 8, e2544, 11 pages).
Regarding instant claims 48 and 50-53, Copending ‘282 claims a method of treatment for pulmonary cystic fibrosis comprising administration of a pharmaceutical composition comprising cysteamine (Copending ‘282 claim 1).
While Copending ‘282 does not specifically teach: (i) the treatment of hyperinflammation; (ii) or IV or oral administration of the cysteamine composition; the teachings of Thoene, Buiser, and Ferrari are relied upon for these disclosures.
Thoene speaks to a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene speaks to a method of treating infections caused by RNA viruses enterovirus, rhinovirus, coronavirus, measles virus, and mumps virus (Thoene claim 3). Thoene discloses their cysteamine treatment can be administered via injection or orally (page 9, last 2 lines).
Buiser teaches SARS-CoV-2 (a coronavirus) infections lead to cytokine release syndrome (CRS), also known as cytokine storm. CRS has been described as acute inflammatory syndrome (page 2, para. 2, lines 1-3). Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8).
Ferrari teaches cysteamine decreases the production of inflammatory cytokines (page 5, col. 2, para. 2).
Regarding instant claim 48, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘282’s cysteamine formulation for the treatment of cytokine release syndrome (CRS), which is a form of hyperinflammation caused by a coronavirus infection. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘282’s disclosure of a cysteamine formulation Thoene’s teachings that cysteamine is effective for the treatment of coronavirus infections; Buiser’s teachings that SARS-CoV-2 (a coronavirus) leads to cytokine release syndrome and hyperinflammation; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines, thus treating the hyperinflammation whilst treating the coronavirus inflection.
Regarding claim 50-51, Thoene teaches the treatment of viral infections, including pneumonia with cysteamine (Thoene claims 2-3) and Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8). Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘282’s cysteamine formulation for the treatment of inflammation caused by pneumonia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘282’s disclosure of a cysteamine formulation; Thoene’s teachings of the treatment of viral infections, including pneumonia, with cysteamine; Buiser’s teachings that a cytokine inhibitor was effective to treat COVID-19 pneumonia; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines.
Regarding claim 52, Thoene teaches the treatment of influenza with cysteamine, and that symptoms include acute respiratory distress (page 3, lines 1-4). Buiser discloses the symptoms of a COVID-19 infection include acute respiratory distress syndrome (ARDS) (page 3, Laboratory Findings, lines 10-11).
Regarding claim 53, Thoene discloses their cysteamine treatment can be administered via injection or orally (page 9, last 2 lines).
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been introduced.
Claim Objections
Applicant’s arguments, see page 6, filed 12/04/2025, with respect to objection of the claims have been fully considered and are persuasive. The objection of the claims has been withdrawn.
Claim Rejections - 35 USC § 112(b)
Applicant’s arguments, see page 6, filed 12/04/2025, with respect to 35 USC § 112(b) rejection of the claims have been fully considered and are persuasive. The 35 USC § 112(b) rejection of the claims has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Applicant’s amendments.
Claim Rejections - 35 USC § 102
Applicant's arguments filed 12/04/2025 have been fully considered but they are not persuasive.
Applicant argues that incorporation of the limitation “wherein the method comprises inhibiting the activity of glycine decarboxylate” overcomes the rejection because Thoene does not disclose their cysteamine treatment by inhibiting GLDC.
This is not persuasive. As stated in this action, a recitation of the intended use of the claimed invention, such as the “treatment by inhibiting the activity of glycine decarboxylase” in the instant application, must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
In the present case, Thoene discloses treatment of the same class of viral infection by administering the claimed compound. Therefore, the recitation of the mode of action of Thoene’s method of treatment does not render the instant claims patentable.
Furthermore, Applicant is reminded that products of identical chemical composition cannot have mutually exclusive properties." A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 12/04/2025 have been fully considered but they are not persuasive.
Applicant argues that Thoene and Karim fail to disclose cysteamine for treating viral infection by inhibiting the activity of GLDC. Applicant states Thoene and Karim do not disclose treatment wherein plasma concentrations of glycine are lower that 300 µmol/L or wherein GLDC is upregulated. Applicant argues that the action of cysteamine on the GLDC pathway has enabled the identification of a particular sub-group of patients which may be more at risk of higher viral infection. Applicant argues that nothing in Thoene teaches treatment of hyperinflammation in a subject with pneumonia, and that Ferrari does not remedy this deficiency; that Ferrari fails to remedy this deficiency because they speak of bacterial infections in patients with cystic fibrosis (CF), Applicant argues the inflammation pathway of CF is different from that of pneumonia. Applicant argues that Buiser does not remedy the deficiencies of Thoene and Ferrari, because it is drawn to cytokine storm (an acute inflammatory syndrome) also experienced by patients undergoing CAR-T cell therapy in cancer or being treated with an antibody. Applicant argues that inflammatory responses are well described and that Bruiser adds nothing new.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant’s statement that other conditions also cause CRS are not pertinent, since the cited art discloses pneumonia caused by a coronavirus, which is the specific scope of the instant invention.
Regarding Applicant’s arguments that Ferrari relates to bacterial infections in the lung of subjects with cystic fibrosis (CF); Ferrari specifically discloses that cysteamine reduces lung inflammation in vivo and that treatment with cysteamine significantly reduced the levels of inflammatory cytokines in patients, coupled with an amelioration of lung function (page 2, para. bridging col. 1, end). Thus, one of ordinary skill would have been motivated to administer cysteamine to a subject suffering from pneumonia in light of its cytokine inhibiting properties and amelioration of lung function. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings of a method of treating pneumonia and coronavirus infections in a subject, comprising administration of cysteamine; further because Buiser teaches SARS-CoV-2 infections lead to cytokine release syndrome (CRS) and that a cytokine inhibitor is capable of treating COVID-19 pneumonia.
In response to Applicant’s arguments that Thoene and Karim do not disclose treatment wherein plasma concentrations of glycine are lower that 300 µmol/L or wherein GLDC is upregulated:
Thoene discloses a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be herpesvirus, etc., and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene further discloses methods for treating subjects diagnosed with, or susceptible to, viral infections (reading on prophylactic treatment) (page 4, lines 9-10 and 13), including herpesviruses and hepatoviruses (i.e., hepatitis; claim 3 of Thoene).
Karim teaches viral infections constitute a risk factor for developing type 2 diabetes mellitus (T2DM), and teaches that familiar (RNA) viruses associated with these diseases are Hepatitis C (HCV - hepatovirus) and Herpes Simplex virus 1 (Abstract and page 430, para. bridging col. 1 and 2). Karim discloses obesity is the primary cause of T2DM in people who are predisposed with the disease (page 429, col. 2, para. 1, last 3 lines). Karim also teaches some virus infections directly induce T2DM, and suggests that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (conclusion, last 12 lines).
Alves teaches that low plasma glycine concentrations have been consistently reported in association with obesity and T2DM (page 1, last 2 lines). Alves discloses glycine concentrations of about 206 µmol/L in obese patients, and about 211-231 µmol/L in T2DM patients (table 1, page 3, entry 1 and 8) – reading on lower than or equal to 300 µmol/L.
Milind describes how upregulated GLDC activity in rodent models leads to metabolic stress; obesity and diabetes (page vi, last para.; and Chapter 2).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of a viral infection in a subject who is obese with a glycine level that is lower than or equal to 300 µmol/L and with elevated GLDC activity; or to prophylactically administer the cysteamine to the obese subject with glycine level that is lower than or equal to 300 µmol/L or elevated GLDC activity. One of ordinary skill would have been motivated to do so in view of Theone’s disclosure of a method of treatment of viral infections comprising administration of cysteamine; Karim’s teachings that obese patients have a higher risk of T2DM and certain viral infections, like HCV, have been liked to T2DM; and Alves’s disclosure that obese patients have glycine levels of about 206 µmol/L; and Milind teaches that elevated GLDC activity leads to obesity. One of ordinary skill would have had a reasonable expectation of success in view of Thoene’s teachings that cysteamine administration is effective for the treatment and prevention of viral infections; further in view of Karim’s suggestions that treatment and prevention of viral infection can reduce the risk of patients developing T2DM (particularly in obese patients with reduced levels of glycine and elevated levels of GLDC activity, as taught by Alves and Milind, who have a higher risk of T2DM).
In response to Applicant’s arguments that nothing in Thoene teaches treatment of hyperinflammation in a subject with pneumonia, and that Ferrari, do not Busier remedy this:
Thoene discloses a method of treating a viral infection comprising administration of an effective amount of a cysteamine compound, wherein the viral infection can be coronavirus, and wherein the cysteamine compound can be cysteamine or a derivative, conjugate, or metabolite thereof (Thoene claims 1-4). Thoene specifically mentions treatment of pneumonia with their method – reading on the instant claim (Thoene’s claim 3, line 2).
Buiser teaches SARS-CoV-2 (a coronavirus) infections lead to cytokine release syndrome (CRS), also known as cytokine storm. CRS has been described as acute inflammatory syndrome (page 2, para. 2, lines 1-3). Buiser teaches a cytokine inhibitor (tocilizumab), indicated to treat CRS, was approved to treat COVID-19 pneumonia (page 4, lines 6-8).
Ferrari teaches cysteamine decreases the production of inflammatory cytokines (page 5, col. 2, para. 2).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer cysteamine for the treatment of cytokine release syndrome (CRS), which is a form of hyperinflammation caused by a coronavirus infection, such as pneumonia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Thoene’s teachings that cysteamine is effective for the treatment of coronavirus infections, including pneumonia; Buiser’s teachings that SARS-CoV-2 (a coronavirus) leads to cytokine release syndrome and hyperinflammation; and Ferrari’s disclosure that cysteamine is effective at decreasing the production of inflammatory cytokines, thus treating the hyperinflammation whilst treating the coronavirus inflection, such as pneumonia.
Double Patenting
Applicant's arguments filed 12/04/2025 have been fully considered but they are not persuasive.
Applicant requests that rejections be held in abeyance until claims are allowable.
This is not persuasive. Claims stand rejected under the obviousness-type non-statutory double patenting rejections outlined in this final office action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627