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 01/08/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Method of treating hyperinflammation with cysteamine or cystamine.”
Status of the Claims
Claims 48 and 50-53 are pending in this application. Claims 1-47, 49, and 54 have been cancelled by applicant.
Claim Interpretation
The specification discusses hyperinflammation in [0027] and states, for instance: “Hyperinflammation may be the result of viral infection or the result of bacterial or fungal infection. The hyperinflammation may be in acute respiratory distress syndrome (ARDS)”.
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 48 and 50-53 are rejected under 35 U.S.C. 103 as being unpatentable over Fraser-Pitt et al. (Infection and Immunity, 2018, 86, e00947-17, 14 pages) (“Fraser-Pitt”); in view of Holden et al. (mBio, 2016, 7, e01397-16, 10 pages) (“Holden”); further in view of Gotts et al. (Am. J. Physiol. Lung Cell Mol. Physiol. 317: L717–L736, 2019) (“Gotts”).
Regarding claims 48 and 50-52, Fraser-Pitt discloses that cysteamine (hereafter CYS) can potentiate antibiotic therapy against bacterial strains, including Klebisella pneumoniae (hereafter KP) (see Table 3, page 7). Fraser-Pitt suggests that CYS might play a role in inflammation and immunity (last para., page 9).
Regarding claim 53, Frasier-Pitt teaches intravenous administration of CYS (page 2, para. 2, lines 14-15).
While Fraser-Pitt does not specifically teach treatment of hyperinflammation with CYS, the teachings of Holden and Gotts are relied upon for these disclosures.
Holden teaches that KP is responsible for a wide range of infections, including pneumonia; and that siderophores secreted by KP during infection induce cytokine secretion (including IL-6, CXCL1, and CXCL-2) and activates HIF-1α, which controls permeability and inflammatory gene expression. Holden hypothesizes that KP directly contributes to inflammation and bacterial dissemination during pneumonia.
Gotts teaches pneumonia is responsible for more deaths in the United States than any other infectious disease. Severe pneumonia is a common cause of acute respiratory failure and acute respiratory distress syndrome (ARDS) (abstract) – reading on hyperinflammation.
Therefore, regarding claims 48 and 50-52, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a treatment comprising CYS to a subject suffering from hyperinflammation (cytokine storm and/or ARDS) in a subject with pneumonia that is due to a KP infection. One of ordinary skill would have been motivated to do so because Frasier-Pitt teaches CYS administration in conjunction with an antibiotic treatment potentiated the antibiotic efficacy of the treatment, and suggests that CYS might play a role in inflammation treatment. One would have been further motivated because Holden teaches siderophores secreted by KP impact systemic dissemination of bacteria, leading to systemic infections which would exacerbate inflammation and cytokine storm, since Holden also teaches that siderophores secreted by KP induce cytokine secretion and activates HIF-1α, directly contributing to inflammation. One would have been further motivated in view of Gotts’ teaching that severe pneumonia is a common cause of ARDS – a form of hyperinflammation. One of ordinary skill would have had a reasonable expectation of success because Frasier-Pitt teaches CYS coadministration potentiated antibiotic efficacy, reducing the MIC significantly for KP-infection treatment, which would be expected to reduce/ inhibit cytokine secretion, as taught by Holden, and therefore treat the resulting cytokine storm and possible ARDS, as taught by Gotts.
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 50-53 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); in view of Fraser-Pitt et al. (Infection and Immunity, 2018, 86, e00947-17, 14 pages) (“Fraser-Pitt”); in view of Holden et al. (mBio, 2016, 7, e01397-16, 10 pages) (“Holden”); further in view of Gotts et al. (Am. J. Physiol. Lung Cell Mol. Physiol. 317: L717–L736, 2019) (“Gotts”).
Regarding instant claims 48 and 50-52, 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 Fraser-Pitt, Holden, and Gott are relied upon for these disclosures.
Fraser-Pitt discloses that cysteamine (hereafter CYS) can potentiate antibiotic therapy against bacterial strains, including Klebisella pneumoniae (hereafter KP) (see Table 3, page 7). Fraser-Pitt suggests that CYS might play a role in inflammation and immunity (last para., page 9).
Holden teaches that KP is responsible for a wide range of infections, including pneumonia; the specific combination of siderophores secreted by KP during infection can impact tissue localization and systemic dissemination; and that siderophores secreted by KP during infection induce cytokine secretion (including IL-6, CXCL1, and CXCL-2) and activates HIF-1α, which controls permeability and inflammatory gene expression. Holden hypothesizes that KP directly contributes to inflammation and bacterial dissemination during pneumonia.
Gotts teaches pneumonia is responsible for more deaths in the United States than any other infectious disease. Severe pneumonia is a common cause of acute respiratory failure and acute respiratory distress syndrome (ARDS) (abstract) – reading on hyperinflammation.
Therefore, regarding instant claims 48 and 50-52, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a treatment comprising CYS to a subject suffering from hyperinflammation (cytokine storm and/or ARDS) in a subject with pneumonia that is due to a KP infection. One of ordinary skill would have been motivated to do so because US ‘525 discloses their method of treating a bacterial respiratory infection (reading on pneumonia) comprising administration of CYS; Frasier-Pitt teaches CYS administration in conjunction with an antibiotic treatment potentiated the antibiotic efficacy of the treatment, and suggests that CYS might play a role in inflammation treatment. One would have been further motivated because Holden teaches siderophores secreted by KP impact systemic dissemination of bacteria, leading to systemic infections which would exacerbate inflammation and cytokine storm, since Holden also teaches that siderophores secreted by KP induce cytokine secretion and activates HIF-1α, directly contributing to inflammation. One would have been further motivated in view of Gotts’ teaching that severe pneumonia is a common cause of ARDS. One of ordinary skill would have had a reasonable expectation of success because Frasier-Pitt teaches CYS coadministration potentiated antibiotic efficacy, reducing the MIC significantly for KP-infection treatment, which would be expected to reduce/ inhibit cytokine secretion, as taught by Holden, and therefore treat the resulting cytokine storm and possible ARDS, as taught by Gotts.
Regarding claim 53, Frasier-Pitt teaches intravenous administration of CYS (page 2, para. 2, lines 14-15).
Claims 48 and 50-53 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); in view of Fraser-Pitt et al. (Infection and Immunity, 2018, 86, e00947-17, 14 pages) (“Fraser-Pitt”); in view of Holden et al. (mBio, 2016, 7, e01397-16, 10 pages) (“Holden”); further in view of Gotts et al. (Am. J. Physiol. Lung Cell Mol. Physiol. 317: L717–L736, 2019) (“Gotts”).
Regarding instant claims 48 and 50-51, US ‘491 speaks to a method of treatment for a bacterial respiratory infection with P. aeruginosa (hereafter PA) (reading on bacterial pneumonia) by administering a composition comprising cysteamine (US ‘491 claims 1 and 5).
While US ‘491 does not specifically teach the treatment of hyperinflammation, the teachings of Fraser-Pitt, Holden, and Gott are relied upon for these disclosures.
Fraser-Pitt discloses that cysteamine (hereafter CYS) can potentiate antibiotic therapy against bacterial strains, including PA and Klebisella pneumoniae (hereafter KP) (page 6, para. 3; and Table 3, page 7). Fraser-Pitt suggests that CYS might play a role in inflammation and immunity (last para., page 9).
Holden teaches that KP is responsible for a wide range of infections, including pneumonia; the specific combination of siderophores secreted by KP during infection can impact tissue localization and systemic dissemination; and that siderophores secreted by KP during infection induce cytokine secretion (including IL-6, CXCL1, and CXCL-2) and activates HIF-1α, which controls permeability and inflammatory gene expression. Holden hypothesizes that KP directly contributes to inflammation and bacterial dissemination during pneumonia. Holden also discloses models with PA bacterial strains.
Gotts teaches pneumonia is responsible for more deaths in the United States than any other infectious disease. Severe pneumonia is a common cause of acute respiratory failure and acute respiratory distress syndrome (ARDS) (abstract) – reading on hyperinflammation.
Therefore, regarding instant claims 48 and 50-52, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a treatment comprising CYS to a subject suffering from hyperinflammation (cytokine storm and/or ARDS) in a subject with pneumonia that is due to a KP infection. One of ordinary skill would have been motivated to do so because US ‘491 discloses their method of treating a bacterial respiratory infection (reading on pneumonia) comprising administration of CYS; Frasier-Pitt teaches CYS administration in conjunction with an antibiotic treatment potentiated the antibiotic efficacy of the treatment, and suggests that CYS might play a role in inflammation treatment. One would have been further motivated because Holden teaches siderophores secreted by KP impact systemic dissemination of bacteria, leading to systemic infections which would exacerbate inflammation and cytokine storm, since Holden also teaches that siderophores secreted by KP induce cytokine secretion and activates HIF-1α, directly contributing to inflammation. One would have been further motivated in view of Gotts’ teaching that severe pneumonia is a common cause of ARDS. One of ordinary skill would have had a reasonable expectation of success because Frasier-Pitt teaches CYS coadministration potentiated antibiotic efficacy, reducing the MIC significantly for KP-infection treatment, which would be expected to reduce/ inhibit cytokine secretion, as taught by Holden, and therefore treat the resulting cytokine storm and possible ARDS, as taught by Gotts.
Regarding claim 53, Frasier-Pitt teaches intravenous administration of CYS (page 2, para. 2, lines 14-15).
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 Fraser-Pitt et al. (Infection and Immunity, 2018, 86, e00947-17, 14 pages) (“Fraser-Pitt”); in view of Holden et al. (mBio, 2016, 7, e01397-16, 10 pages) (“Holden”); further in view of Gotts et al. (Am. J. Physiol. Lung Cell Mol. Physiol. 317: L717–L736, 2019) (“Gotts”).
Regarding instant claims 48 and 50-53, US ‘660 speaks to a method of treatment for lung disease, including pneumonia, comprising administration of a pharmaceutical composition comprising cysteamine (US ‘660 claims 1 and 16-18). 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 Fraser-Pitt, Holden, and Gott are relied upon for these disclosures.
Fraser-Pitt discloses that cysteamine (hereafter CYS) can potentiate antibiotic therapy against bacterial strains, including Klebisella pneumoniae (hereafter KP) (page 6, para. 3; and Table 3, page 7). Fraser-Pitt suggests that CYS might play a role in inflammation and immunity (last para., page 9).
Holden teaches that KP is responsible for a wide range of infections, including pneumonia; the specific combination of siderophores secreted by KP during infection can impact tissue localization and systemic dissemination; and that siderophores secreted by KP during infection induce cytokine secretion (including IL-6, CXCL1, and CXCL-2) and activates HIF-1α, which controls permeability and inflammatory gene expression. Holden hypothesizes that KP directly contributes to inflammation and bacterial dissemination during pneumonia.
Gotts teaches pneumonia is responsible for more deaths in the United States than any other infectious disease. Severe pneumonia is a common cause of acute respiratory failure and acute respiratory distress syndrome (ARDS) (abstract) – reading on hyperinflammation.
Therefore, regarding instant claims 48 and 50-52, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a treatment comprising CYS to a subject suffering from hyperinflammation (cytokine storm and/or ARDS) in a subject with pneumonia that is due to a KP infection. One of ordinary skill would have been motivated to do so because US ‘660 discloses their method of treating a bacterial respiratory infection (reading on pneumonia) comprising administration of CYS; Frasier-Pitt teaches CYS administration in conjunction with an antibiotic treatment potentiated the antibiotic efficacy of the treatment, and suggests that CYS might play a role in inflammation treatment. One would have been further motivated because Holden teaches siderophores secreted by KP impact systemic dissemination of bacteria, leading to systemic infections which would exacerbate inflammation and cytokine storm, since Holden also teaches that siderophores secreted by KP induce cytokine secretion and activates HIF-1α, directly contributing to inflammation. One would have been further motivated in view of Gotts’ teaching that severe pneumonia is a common cause of ARDS. One of ordinary skill would have had a reasonable expectation of success because Frasier-Pitt teaches CYS coadministration potentiated antibiotic efficacy, reducing the MIC significantly for KP-infection treatment, which would be expected to reduce/ inhibit cytokine secretion, as taught by Holden, and therefore treat the resulting cytokine storm and possible ARDS, as taught by Gotts.
Regarding claim 53, Frasier-Pitt teaches intravenous administration of CYS (page 2, para. 2, lines 14-15).
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); in view of Fraser-Pitt et al. (Infection and Immunity, 2018, 86, e00947-17, 14 pages) (“Fraser-Pitt”); in view of Holden et al. (mBio, 2016, 7, e01397-16, 10 pages) (“Holden”); further in view of Gotts et al. (Am. J. Physiol. Lung Cell Mol. Physiol. 317: L717–L736, 2019) (“Gotts”).
Regarding instant claims 48 and 50-53, US ‘568 speaks to a method of treatment for lung disease, including pneumonia 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 Fraser-Pitt, Holden, and Gott are relied upon for these disclosures.
Fraser-Pitt discloses that cysteamine (hereafter CYS) can potentiate antibiotic therapy against bacterial strains, including Klebisella pneumoniae (hereafter KP) (page 6, para. 3; and Table 3, page 7). Fraser-Pitt suggests that CYS might play a role in inflammation and immunity (last para., page 9).
Holden teaches that KP is responsible for a wide range of infections, including pneumonia; the specific combination of siderophores secreted by KP during infection can impact tissue localization and systemic dissemination; and that siderophores secreted by KP during infection induce cytokine secretion (including IL-6, CXCL1, and CXCL-2) and activates HIF-1α, which controls permeability and inflammatory gene expression. Holden hypothesizes that KP directly contributes to inflammation and bacterial dissemination during pneumonia.
Gotts teaches pneumonia is responsible for more deaths in the United States than any other infectious disease. Severe pneumonia is a common cause of acute respiratory failure and acute respiratory distress syndrome (ARDS) (abstract) – reading on hyperinflammation.
Therefore, regarding instant claims 48 and 50-52, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a treatment comprising CYS to a subject suffering from hyperinflammation (cytokine storm and/or ARDS) in a subject with pneumonia that is due to a KP infection. One of ordinary skill would have been motivated to do so because US ‘660 discloses their method of treating a bacterial respiratory infection (reading on pneumonia) comprising administration of CYS; Frasier-Pitt teaches CYS administration in conjunction with an antibiotic treatment potentiated the antibiotic efficacy of the treatment, and suggests that CYS might play a role in inflammation treatment. One would have been further motivated because Holden teaches siderophores secreted by KP impact systemic dissemination of bacteria, leading to systemic infections which would exacerbate inflammation and cytokine storm, since Holden also teaches that siderophores secreted by KP induce cytokine secretion and activates HIF-1α, directly contributing to inflammation. One would have been further motivated in view of Gotts’ teaching that severe pneumonia is a common cause of ARDS. One of ordinary skill would have had a reasonable expectation of success because Frasier-Pitt teaches CYS coadministration potentiated antibiotic efficacy, reducing the MIC significantly for KP-infection treatment, which would be expected to reduce/ inhibit cytokine secretion, as taught by Holden, and therefore treat the resulting cytokine storm and possible ARDS, as taught by Gotts.
Regarding claim 53, Frasier-Pitt teaches intravenous administration of CYS (page 2, para. 2, lines 14-15).
Response to Arguments
Claims
Claim amendments are acknowledged and have been entered. No new matter has been introduced.
Claim Rejections - 35 USC § 112(b)
In view of claim amendments, 35 USC § 112(b) rejections have been withdrawn.
Claim Rejections - 35 USC § 102
In view of claim amendments, 35 USC § 102 rejections have been withdrawn.
Claim Rejections - 35 USC § 103
Applicant’s arguments, see pages 3-9, filed 05/11/2026, with respect to the 35 USC § 103 rejections have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Frasier-Pitt in view of Holden, further in view of Gott.
See comments regarding affidavit below.
Affidavit Traversing Rejections – filed 05/11/2026
The Affidavit under 37 CFR 1.132 filed 05/11/2026 is sufficient to overcome the rejections presented in the final Office action filed 01/09/2026; however, the Affidavit under 37 CFR 1.132 filed 05/11/2026 is insufficient to overcome the rejections presented herein.
Applicant states patients treated with cysteamine had a 94% posterior probability of benefit of reduced stary in ICU and time on organ support.
This result is not surprising in view of the art cited herein. Specifically, Fraser-Pitt teaches CYS potentiates antibiotic therapy against bacterial strains, including KP (page 6, para. 3; and Table 3, page 7). Fraser-Pitt suggests that CYS might play a role in inflammation and immunity (last para., page 9). Holden hypothesizes that KP directly contributes to inflammation and bacterial dissemination during pneumonia. And Gotts teaches pneumonia is a common cause of acute respiratory failure and acute respiratory distress syndrome (ARDS) – reading on hyperinflammation. Therefore, one of ordinary skill would expect that treatment comprising CYS would have a benefit in subjects suffering from ARDS linked to bacterial pneumonia.
Double Patenting
Applicant’s arguments, see pages 3-9, filed 05/11/2026, with respect to the non-statutory double patenting (NSDP) rejections in view of Endeman and Ferrari; or Sadikot in view of Ferrari; or Thoene in view of Buiser further in view of Ferrari; have been fully considered and are persuasive. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made as presented herein. Upon further consideration, the previously presented provisional NSDP rejection over Copending ‘282 (now US Patent No. 12,576,050 B2) has been withdrawn.
Conclusion
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
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