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 .
Claims 41-60 are pending and under consideration.
Priority
The instant application is a CON of US Application No. 17/240,558 filed on 4/26/2021, now US Pat. No. 11,931,418.
Information Disclosure Statement
The Information Disclosure Statement filed on 10/1/2024 has been considered.
Title
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 title recites “DENDRIMER COMPOSITIONS AND METHODS FOR TREATMENT OF SEVERE ACUTE RESPIRATORY DISTRESS SYNDROME”. The following title, for example, is suggested: A METHOD OF TREATING……..”
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figure 1 is not clear and dark enough to read. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Claim Objections
Claims 42-43 are objected to because of the following informalities: claims 42-43 are objected for the use of abbreviated phrases (IFN-γ, TNF-α, IL-1β, IL-6,….. and many others), which should be described for the first time followed by an abbreviated form placed in a bracket.
. Appropriate correction is required.
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 nonobviousness.
Claim(s) 41-60 are rejected under 35 U.S.C. 103 as being unpatentable over Nance et al. (IDS, Biomaterials 101: 96-107, 2016) in view of Kannan et al. (IDS, J. of Internal Med. 276: 579-617, 2014).
A method of treating one or more symptoms of severe inflammation arising from a viral infection, the method comprising: administering to a subject in need thereof an effective amount of a composition comprising hydroxyl-terminated dendrimers conjugated to N-acetyl cysteine, wherein the severe inflammation comprises systemic inflammation in the subject, wherein the severe inflammation is associated with elevated levels of one or more markers selected from the group consisting of C-reactive protein (CRP), ferritin, IFN-y, TNF-a,IL-1p,IL-6, IL-12, IL-18, CXCL-1, CXCL-5, CXCL-8, and CCL-2 (claim 42-43). The method of claim 41, wherein the severe inflammation is associated with acute lung injury and/or acute respiratory distress syndrome (claim 44). The method of claim 41, wherein the severe inflammation is associated with overreactive M1 macrophages (claim 45). The method of claim 41, wherein the severe inflammation comprises neuroinflammation in the subject (claim 46). The method of claim 41, wherein the severe inflammation is associated with a cytokine storm. The method of claim 41, wherein the viral infection is a pathogenic viral infection. The method of claim 41, wherein the viral infection is caused by infection with a coronavirus. The method of claim 49, wherein the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The method of claim 41, wherein the dendrimers comprise generation 4, generation 5, or generation 6 poly(amidoamine) dendrimers, wherein the dendrimers comprise generation 4 poly(amidoamine) dendrimers (claim 52). The method of claim 41, wherein the composition is administered intravenously, subcutaneously, or intramuscularly (claim 53), wherein the composition is administered in an amount between about 0.1 and about 40 mg/kg body weight of the subject (claim 54). The method of claim 54, wherein the composition is administered in an amount between about 1.0 and about 20 mg/kg body weight of the subject (claim 55). The method of claim 55, wherein the composition is administered in an amount between about 2.0 and about 10 mg/kg body weight of the subject (claim 56). The method of claim 41, wherein the composition is administered intravenously in an amount between about 2.0 and about 10 mg/kg body weight of the subject (claim 57). The method of claim 57, wherein the composition is administered by intravenous infusion. The method of claim 41, wherein the composition is administered subcutaneously in an amount between about 2.0 and about 10 mg/kg body weight of the subject. The method of claim 41, further comprising administering one or more additional therapeutic agents to the subject.
It is noted to applicants that the dendrimer conjugated with NAC treats inflammation including neuroinflammation, any infection that results in inflammation would be treatable by dendrimer conjugated with NAC, unless evidence to contrary.
Nance et al. teach dendrimer-mediated targeting of neuroinflammation (see the title). They teach systemically administration of dendrimers to treat neuroinflammation (abstract). They teach that dendrimer of poly(amidoamine) (PAMAM) generation 4 (G4-OH) can cross even blood brain barrier and therefore, it can be used for treating neuroinflammatory diseases in the brain. They teach dendrimers conjugated with NAC for treating neuroinflammation (pg. 2, 2nd paragraph). They teach that G4-OH is able to rapidly diffuse several millimeters away from the point of injection within 4 hours and localize in regions of injury (pg. 9, 3.4 Movement…and 3.5. Dendrimer uptake..). They teach that systemic administration of dendrimer-NAC containing up to 55 dendrimer and 10 mg NAC results in significant and profound efficacy in newborn rabbits with CP (pg. 10, 3.6. Semi-quantitative …).
Kannan et al teach many examples of dendrimer based nanomedicine for clinical applications (abstract, title and Table 1). They teach use of dendrimers with linker to attach various therapeutics (Fig. 4) and the use in inflammation therapeutics such as arthritis, cancer, neurodegeneration and cardiovascular (pg. 598). They teach administering 8 mg/kg of dendrimer complexed with indomethacin. They teach administering more than one therapeutic such as folic acid and methotrexate for treating inflammation (pg. 598, right col.). They teach single dose of D-NAC treats cerebral palsy (Table 2). It is well known in the art to combine medicines being used for similar benefits (metformin and GLP-agonist to control blood glucose). Regarding claim 53, they teach that the administration of dendrimers intravenously enhanced tolerable doses, bioavailability and prolonged survival of mice having melanoma (pg. 604, Cancer). It is noted that use of pH 5.5 to release dendrimers is well known in the art (see Kannan et al. US 20170119899, paragraph [0243]). The reference Kannan et al. US 20170119899 is to support the skill of the art and not as a prior art. Additionally, citrate buffer or histidine buffer is functionally the same that results in the same pH 5.5.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use dendrimers conjugated with NAC for reducing one or more severe inflammation in an organ of a subject in combination with another therapeutic agents as taught by Kannan et al in doses of 8 mg/kg to about 65 mg/kg as taught by Nance et al. Additionally, one would have been motivated to do so because Nance et al. and Kannan et al teach that dendrimers conjugated with NAC have successfully been used for treating inflammation in cardiovascular, arthritis and neuroinflammatory diseases. Further, one would have a reasonable expectation of success in using dendrimers conjugated with N-acetyl cysteine for treating one of more symptoms of severe inflammation in an organ of a subject because Nance et al. and Kannan et al teach treating inflammatory conditions including neuroinflammation with dendrimers conjugated with NAC. Therefore, the instant rejection would have been obvious over the combined teachings of the prior art.
Generally, differences in concentrations of components of a formulation, timing dosages or pH of a composition will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
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 41-60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,931,418. Although the claims at issue are not identical, they are not patentably distinct from each other because a method of treating one or more symptoms of severe inflammation arising from a viral infection, the method comprising: administering to a subject in need thereof an effective amount of a composition comprising hydroxyl-terminated dendrimers conjugated to N-acetyl cysteine, wherein the severe inflammation comprises systemic inflammation in the subject, wherein the severe inflammation is associated with elevated levels of one or more markers selected from the group consisting of C-reactive protein (CRP), ferritin, IFN-y, TNF-a,IL-1p,IL-6, IL-12, IL-18, CXCL-1, CXCL-5, CXCL-8, and CCL-2, wherein the severe inflammation is associated with acute lung injury and/or acute respiratory distress syndrome (claim 44), wherein the severe inflammation is associated with overreactive M1 macrophages (claim 45). The method of claim 41, wherein the severe inflammation comprises neuroinflammation in the subject, wherein the severe inflammation is associated with a cytokine storm. The method of claim 41, wherein the viral infection is a pathogenic viral infection, wherein the viral infection is caused by infection with a coronavirus. The method of claim 49, wherein the coronavirus is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), wherein the dendrimers comprise generation 4, generation 5, or generation 6 poly(amidoamine) dendrimers, wherein the dendrimers comprise generation 4 poly(amidoamine) dendrimers (claim 52), wherein the composition is administered intravenously, subcutaneously, or intramuscularly (claim 53), wherein the composition is administered in an amount between about 0.1 and about 40 mg/kg body weight of the subject (claim 54), wherein the composition is administered in an amount between about 1.0 and about 20 mg/kg body weight of the subject (claim 55), wherein the composition is administered in an amount between about 2.0 and about 10 mg/kg body weight of the subject (claim 56), wherein the composition is administered intravenously in an amount between about 2.0 and about 10 mg/kg body weight of the subject (claim 57), wherein the composition is administered by intravenous infusion. The method of claim 41, wherein the composition is administered subcutaneously in an amount between about 2.0 and about 10 mg/kg body weight of the subject. The method of claim 41, further comprising administering one or more additional therapeutic agents to the subject are taught by claims 1-29 of U.S. Patent No. 11,931,418.
Conclusion
No claims is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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