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 .
Status of Application
Applicants' arguments/remarks filed 10/20/2025 are acknowledged. Claims 1-45 are previously and newly canceled. Claims 46-59 are newly added. Claims 46-59 are examined on the merits within and are currently pending.
Withdrawn Rejections
With applicants' amendment, filed 10/20/2025:
the 35 U.S.C. § 102(a)(1) rejection of Claims 1, 3, 7, 12 and 13 has been withdrawn in view of the cancellation of the claims;
the 35 U.S.C. § 103 rejection of Claims 1 and 6 has been withdrawn in view of the cancellation of the claims;
the 35 U.S.C. § 103 rejection of Claims 1 and 8-11 has been withdrawn in view of the cancellation of the claims;
the 35 U.S.C. § 103 rejection of Claims 19, 21, 22, 25, 26, 28, 30, 34-35, and 44-45 has been withdrawn in view of the cancellation of the claims;
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claim(s) 46-59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Campbell et al. (US 20210322412Al), in view of McGrath et al. (US 20120134929Al) and Ogata (US008486431B2).
Claims 46-50,
Campbell et al. teach the invention provides methods of reducing activity of inflammatory macrophages in a patient suffering from a coronavirus infection. The method comprises administering to a patient in need thereof an effective amount of a compound having inhibitory activity towards both the chemokine receptor 2 and the chemokine receptor 5, in order to reduce activity of inflammatory macrophages. (0113). The coronavirus infection may be, for example, an infection by SARS-CoV-2, (0063). In certain embodiments, the patient has acute respiratory distress syndrome. (0124). (ARDS).
Campbell et al. do not teach contacting the subject with a therapeutically effective amount of a chlorite composition to regulate one or more functional properties of the macrophage.
Ogata teaches a method of controlling floating virus infection. The method includes the step of: supplying chlorine dioxide gas into a space where floating virus can be present, (Abs), in
infected person with a certain type of respiratory virus, which is a generic name for various viruses which cause respiratory diseases such as pneumonia, including SARS virus, corona virus. (Col. 1, line 20-35).
Ogata does not teach inappropriate macrophage activation, and the contacting results in reduction of the inappropriate macrophage activation.
McGrath et al. teach: a method of treating a macrophage related disease comprising administering to a subject in need thereof an effective amount of an oxidative agent or an immunosuppressive agent and a method of modulating macrophage accumulation or activation comprising administering to a subject in need thereof an effective amount of an oxidative agent. The oxidative agent can be chlorite or a chlorite containing compound. (Abs). Macrophage related diseases that are treated by the invention include acute respiratory distress syndrome. (0009).
Campbell et al. teach Methods for Reducing Activity of Inflammatory Macrophages in a Patient Suffering from a Coronavirus Infection Using a Compound With Dual CCR2 and CCR5 Inhibitory Activity. (0112-0113).
McGrath et al. teach:
although macrophages play a vital role in host immune defenses, activated macrophages are also involved in the progression of a number of diseases and disorders. Activated macrophages elicit massive leukocyte infiltration and flood the surrounding tissue with inflammatory mediators, pro-apoptotic factors, and matrix degrading proteases. These actions can result in inflammation that can dismantle tissues to the point of inflicting serious injury. (0003). Oxidative agents such as chlorite can return macrophages to their inactivated state. Immunosuppressant agents can mitigate macrophage activation. The present invention provides methods for the treatment of macrophage related diseases and related conditions with oxidative agents or immunosuppressant agents. (0004). In some embodiments, modulating of macrophage activation or accumulation according to the invention comprises modulating one or more molecules involved in one or more cellular pathways selected from the group consisting of interleukin (IL)-1, interleukin-I receptor antagonist sIL1Ra (0020), interleukin-I receptor antagonist IL1Ra, osteopontin, (0228).
when the primed macrophage subsequently encounters an appropriate stimulus, such as bacterial LPS, it becomes classically activated. (0219). These events are followed closely by a significant change in cellular morphology and a dramatic alteration in the secretory profile of the cell like a variety of chemokines including IP-10/CXCLl0. (0220). In some embodiments, the present invention provides a method for treating a macrophage related disease with an oxidative agent or an innnunomodulatory agent by modulating release of chemokines including but not limited to IP-10/CXCLl0. (0222). CXCLl0 is C-X-C motif chemokine ligand 10.
McGrath et al. teach NF-KB (nuclear factor kappa-light-chain-enhancer of activated B cells; NFkB) is a dimeric protein complex that controls DNA transcription. NF-KB is a rapid responder to cellular stimuli such as bacterial or viral antigens. NF-KB plays a key role in regulating the immune response to infection. Improper regulation of NF-KB has been linked to viral infection, and improper immune development. NF-KB is one of the most crucial transcription factors regulating the inflammatory repertoire of macrophages, particularly their expression of proinflammatory cytokines, co stimulatory molecules, and other activation markers in response to diverse environmental cues ( e.g., stress signals, inflammatory cytokines, pathogens. (0203).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention, to reduce activity of inflammatory macrophages in a patient suffering from a coronavirus or SARS-CoV-2 infection by administering to a patient in need thereof an effective amount of a compound having inhibitory activity towards both the chemokine receptor 2 and the chemokine receptor 5, in order to reduce activity of inflammatory macrophages, taught by Campbell et al., which cause the patient ARDS taught by Campbell et al. and McGrath et al. and by administering to a subject in need thereof an effective amount of an oxidative agent, chlorite or chlorine dioxide, taught by Ogata and McGrath et al., or an immunosuppressive agent and a method of modulating macrophage accumulation or activation comprising administering to a subject in need thereof an effective amount of an oxidative agent. chlorite or a chlorite containing compound., to reduce macrophage activation from inflammation factors including interleukin (IL)-1, interleukin-I receptor antagonist IL1Ra, osteopontin, or NF-KB linked to viral infection, taught by McGrath et al., since they have proven macrophage activation in coronavirus/ SARS-CoV-2 infection, which can be regulated by oxidative agent chlorite.
With regard to claims 51-52,
McGrath et al. teach in some embodiments, the pH adjusting compound is any one or more of monosodium phosphate, disodium phosphate. (0081).
With regard to claims 53-54 and 56
McGrath et al. teach the formulations are less toxic to a subject than previously reported chlorite formulations at the same concentration of chlorite, when administered by parenteral, or intravenous administration. (0101).
With regard to claim 55,
McGrath et al. teach Chlorite can be administered on a daily basis. In some embodiments, chlorite is administered on a daily basis at a dose of about 0.2 mg/kg/day of chlorite to about 3.3 mg/kg/day of chlorite. In some embodiments, chlorite is administered on a daily basis at a dose of about 0.2 mg/kg/day to 3.5 mg/kg/day. (0166).
With regard to claim 57,
McGrath et al. teach in some embodiment the oxidative agent is sodium chlorite. (0030).
With regard to claim 58,
The teachings of McGrath et al. are described in Claim 1. The formulations may have differing concentrations of chlorite: 1µM-1.5M. (0085). With exemplary doses of chlorite-containing formulations can vary between about 0.1 ml/kg to about 1.5 ml/kg, preferably about 0.5 ml/kg of body weight. (p164). With an average person of 70Kg, the volumes to dose between about 7 mL to about 35 mL. The method of treatment is intended for intravenous infusion. (0064).
McGrath et al. do not teach wherein the chlorite is administered to the subject for at least 30-minute period.
Time to infuse intravenously varies depending on toxicological levels, efficacy levels, dosing volume and concentration needed for different body weights of patients. For example, For Patients With Multifocal Motor Neuropathy (MMN),with Body Weight from 10-120Kg, infusing rates can be 0.5-5.4 mL/kg/hr, if initial infusion rate is well tolerated, the infusion rate can be increased until up to 5.4 mL/kg/hr. With infusion rate 0.5 mL/kg/hr, 0.5mL/kg / 0.5 mL/kg/hr = 1hr to dose. With infusion rate is increased 1 mL/hr, 0.5mL/kg / 5.4 mL/kg/hr = 0.5 hr to dose. The time to dose can be 30 mins, or 1 hr to dose. (GAMMAGARD LIQUID [Immune Globulin Infusion (Human)] 10% Solution Infusion Rate Table. Takeda. https://www.gammagard.com/Content/hcp/pdf/infusion-rate-table.pdf).
With regard to claim 59,
McGrath et al. teach Chlorite can be administered on a daily basis. (0166). In some embodiments, the first period of time is about one week, the first number of times is about five, the second period of time is about two weeks. (0167).
Response to Arguments
Rejections Under §103
Applicant argues that the enclosed claims 46-58 are not obvious over the combination of the cited references at least because the combination fails to teach or suggest each and every element of the claimed invention and there is no evidence or teaching that the combination would a predicted success.
Applicant's arguments have been fully considered but they are not persuasive since because the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). When the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012). Specifically, in this claim 46, Campbell teaches reducing activity of inflammatory macrophages in a patient suffering from a coronavirus infection; Ogata teaches chlorine dioxide
controlling floating virus infection and McGrath teach reducing macrophage activation through inflammatory factors XCCL10, OL1Ra, OPN or NF-KB by chlorite, so it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to treat SARS-CoV-2 infection by reducing inflammation macrophage activation with factors including interleukin (IL)-1, interleukin-I receptor antagonist IL1Ra, osteopontin, or NF-KB linked to viral/SARS-CoV-2 infection by oxidative agent chlorite, taught by Campbell, Ogata and McGrath, since they have proven macrophage activation in coronavirus/ SARS-CoV-2 infection, and chlorite regulating macrophage activation controlling floating virus infection.
Conclusion
Applicants' 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 extension fee 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 date of this final action.
Correspondence
No claim is allowed.
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/NGOC-ANH THI NGUYEN/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615