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 1-3, 7, 10-11, 13, 18-19, 23, 25-30, 34, 41, 46, 55, 85, 88-95 and 100-101 are pending.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 12/03/25 is acknowledged. The traversal is on the ground(s) that searching and examination of all pending claims (Groups I-IV) would not present serious burden to the Examiner. This is not found persuasive because as shown in the Restriction Requirement filed on 09/03/25, different Groups of claims are directed to different inventions and contain different limitations.
In response to the Species Election Requirement, Applicant elected, “a bacterial and/or fungal infection” as the secondary infection (which is not an election of a specific infection), “remdesivir” as the antimicrobial agent, and “autoimmune diseases” as the pre-existing condition.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 1-3, 7, 10-11, 13, 18, 19, 23, 25-30, 85, 88-95 and 100-101 including the elected species are under examination herein. Claims 34, 41, 46 and 55 are withdrawn.
Claim Objections
Claims 1, 13, 18, 25, 91 are objected to because of the following informalities:
In claim 1, the abbreviation BisEDT should be spelled out with its full name. Although this is done in claim 2, the first recitation of each abbreviation should be spelled out.
Claims 13, 18, 25 and 91 contain chemical, disease or infection names that are capitalized.
Appropriate correction is required.
Duplicate Claim Objections
Claim 85 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 2. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 85 and 100 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating or reducing severity of a symptom of viral respiratory infection or cytokine storm in a subject, does not reasonably provide enablement for preventing the said conditions.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Formal, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, relative skill level, and breadth of the claims
The instant invention is directed to methods of preventing, treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject or preventing cytokine storm, by administering via inhalation, a composition comprising BisEDT microparticles to the subject.
The complex nature of the claims is greatly exacerbated by the breath of the claims. The claims encompass broad ways that the claimed composition prevents all reparatory viral infections and cytokine storm. The relative skill of those in the art is high, that of an MD or PHD.
The state and predictability of the art
The state of the art recognizes that inhalation of compositions comprising BisEDT can treat or lessen the severity of viral respiratory infections and cytokine storm.
The lack of significant guidance from the specification or the prior art with regard to preventing viral respiratory infections utilizing the claimed compoistion makes practicing the scope of the invention unpredictable. Prevention as defined by medical dictionary means: “Action so as to avoid, forestall, or circumvent a happening, conclusion, or phenomenon (for example, disease prevention)” (see http://medical-dictionary.thefreedictionary.com/prevention). And ‘to prevent’ means: “To keep from happening” (see http://www.thefreedictionary.com/prevent).
The claims are thus very broad insofar as they recite prevention of a viral respiratory infection of cytokine storm, i.e., the complete eradication of the same. While such “prevention” might theoretically be possible under strictly controlled laboratory conditions, as a practical matter it is nearly impossible to achieve in the “real world” in which patients live; viral respiratory infections are always a risk.
The amount of direction or guidance provided and the presence or
absence of working examples
The specification provides no direction or guidance for preventing viral respiratory infections. Due to the vastness of ways, conditions and reasons, a subject can acquire viral respiratory infection, one of ordinary skill would not be able to predict or prevent all conditions that would normally result in a viral respiratory infection in a subject.
The quantity of experimentation necessary
Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed composition could be predictably used to prevent viral respiratory infections and cytokine storm by the claim and contemplated by the specification.
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 2, 10, 13, 25, 28, 85, 91-92 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.
Claims 2 and 85 are indefinite for reciting a limitation that does not have full utility. Claims 2 and 85 recite particles (droplets) with a D90 of less than about 2 microns. This limitation encompasses D90 of 0 microns or 0.000001 microns which are neither possible nor envisioned or disclosed.
Claim 10 is indefinite for reciting a concentration of greater than about 0.1 mg/mL. This is also indefinite because the claim as written does not provide an upper limit and as such encompasses values such as 100 mg/mL, 10000 mg/mL, up to infinity, none of which are either disclosed or possible.
Claim 13 is indefinite for reciting “the method of any claim 3”.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 13 recites the broad recitation pneumonia, and the claim also recites 1- ventilator acquired- pneumonia, 2- hospital acquired pneumonia, 3-community acquired pneumonia and 4- viral pneumonia which is the narrower statement of the range/limitation. Claim 13 further recites the broad recitation bronchiectasis infection, and the claim also recites ventilator associated bronchiectasis, which is the narrower statement of the range/limitation. Claim 13 also recites the broad recitation bronchiolitis, and the claim also recites viral bronchiolitis which is the narrower statement of the range/limitation. Claim 13 further recites the broad recitation lower respiratory tract infection, and the claim also recites all other infections that can be lower tract respiratory infections, and which are the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 13 is further indefinite for reciting a secondary infection of claim 3 (i.e. a bacterial or fungal infection) that is bronchitis, viral pneumonia, viral bronchiolitis, and post-lung transplantation. This, bronchitis is an inflammatory condition and not a bacterial or fungal infection. Viral pneumonia and viral bronchiolitis are viral and not bacterial or fungal infections and post-lung transplantation is not a disease or infection.
Claim 25 is indefinite for reciting a long list of antimicrobial agents, which do not have antimicrobial capabilities, including, berberine, simvastatin, dasatinib, metformin, caffeine, imatinib, formoterol, omeperazole, etc. The long list has not been fully reviewed for correctness.
Claim 25 is indefinite for reciting agents with their abbreviations and without their proper chemical names such as ABT-263, CR-31-B(-), N-MCT, AVN-944.
Claim 25 is further indefinite for reciting drugs/ agents that are chemical names and those that are the brand names (Trade names).
Claim 25 is further indefinite for reciting drugs/ agents in the parenthesis. Limitation placed in a parenthesis are not considered part of the claim.
Claim 25 is further indefinite for reciting (e.g herbacetin, rhoifilin, pectolinarim). Recitation of terms including “for example” or “such as” or “preferably” are not acceptable terms in claim language as they render the scope indefinite.
Claim 28 is indefinite for reciting “diffraction pattern is substantially similar to Fig. 44”. Claims are required to be complete on their own and not refer to the Specification or drawings.
Claim 91 is indefinite for reciting “one or more conditions selected from one or more of the group consisting of…”. This is indefinite because it is not clear how many conditions or group of conditions are encompassed by the claim.
Claim 91 is also indefinite because it is not clear how depression is considered a chronic inflammatory condition.
Claim 92 recites the limitation "a secondary infection" in method of claim1. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not support a secondary infection.
In claim 93, the recitation of “secondary infection in the subject is prior to the respiratory viral infection” is vague and not in proper English.
Claim 94 recites the limitation "the secondary infection" in method of claim1. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not support a secondary infection.
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.
Claims 1-3, 7, 10-11, 13, 18, 23, 25-30, 85, 88-95 and 100-101 are rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 20160375034) in view of Saha et al (US 20110092589).
Baker et al teach compositions and methods, including microparticulate suspensions, for treating natural surfaces that contain bacterial biofilm, including unexpected synergy or enhancing effects between bismuth-thiol (BT) compounds and certain antibiotics, to provide formulations for treatment of infections (See abstract and [0032]).
Regarding claims 1 and 85, Baker et al teach bismuth-thiol compositions comprising substantially monodisperse microparticulate suspensions, and methods for their synthesis and use (See [0034]). Baker et al disclose making an acidic aqueous liquid formulations comprising bismuth-thiol (BT), and wherein such liquid particles have a uniformity in particle size (See [0091]-[0092]). The said BT composition comprises one or more BT compounds selected from BisBAL, BisEDT (1,2-ethanedithiol), etc; (See [0037]-[0038], [0043], [0191], [0196] and claim 3). The said natural surfaces include respiratory tract (See [0023], [0037] and claim 3). The microparticulate BT compositions can also be delivered through intranasal drug delivery systems for local, systemic, and nose-to-brain medical therapies (See [0181]). The administration is through one or more epithelial tissue surfaces present in respiratory (e.g., airway, nasopharyngeal and laryngeal paths, tracheal, pulmonary, bronchi, bronchioles, alveoli, etc.) surfaces (See [0196]). The formulation can be administered using nasal sprays, inhalers, nebulizers (See [0181]).
Regarding claims 1-2, 7 and 85, Baker et al teach a liquid or aerosol suspension of microparticles containing one or more BT compounds disclosed herein having a VMD from about 0.5 microns to about 5 microns, or a liquid or aerosol suspension having a VMD or MMAD from about 0.7 microns to about 4.0 microns, including 1.5 and 2.0 microns. The said preparation is “substantially” monodisperse, wherein “substantially” all of the microparticles have a volumetric mean diameter (VMD) within a specified range (e.g., from about 0.4 μm to about 5 μm). For example, at least 90% or more of the particles have a VMD that is within the recited size range (See [0094]-[0095]).
Regarding claims 1-3 and 92-93, Baker et al teach the said method protects a natural surface against one or more of a bacterial pathogen, a fungal pathogen and a viral pathogen, comprising contacting the surface with an effective amount of a BT composition (See [0035]).
Regarding claims 1 and 10, Baker et al teach a composition for treating a subject comprising a therapeutically effective amount of BT of from about 0.001 to about 100 mg/kg body weight of the subject or from 0.001 to 30% by weight (See [0176], [0221] and [0238]). Baker et al tested BisEDT against bacteria and showed activity at 2 µg/mL and 0.5 µg/mL (See [0287]-[0288]). The said formulations may comprise additives including polysorbate surfactants such as Tween® 80 (See 0211]). The said additives may be included at from about 0.01% to about 20% of the total weight of the topical formulation (See [0215]). The liquid formulations may comprise a buffer such as a phosphate and a pH of from 5.5 to about 8.5 (See [0168], [0233] and [0230]). The liquid pharmaceutical compositions, including suspensions may include one or more of the following adjuvants: sterile diluents such as water for injection, saline solution, preferably physiological saline, Ringer's solution, isotonic sodium chloride, etc, (See [0168]).
Regarding claim 11, Baker et al teach the method and composition of claim 1, which would be expected to have the same or similar half-life when deposited in the deep lung.
Regarding claim 13, Baker et al teach that the said BT compounds have proven activity against and can treat bacterial and/or fungal infections, such as MRSA (methicillin resistant S. aureus), MRSE (methicillin resistant S. epidermidis), Mycobacterium tuberculosis, drug-resistant P. aeruginosa, E. coli, Klebsiella pneumoniae, Heliobacter pylori, Legionella pneumophila, Enterococcus faecalis, etc, as well as cytomegalovirus, herpes simplex virus type 1 (HSV-1) and HSV-2, and yeasts and fungi, such as Candida albicans. BT roles have also been demonstrated in reducing bacterial pathogenicity, inhibiting or killing a broad spectrum of antibiotic-resistant microbes (gram-positive and gram-negative), preventing biofilm formation, preventing septic shock, treating sepsis, and increasing bacterial susceptibility to antibiotics to which they previously exhibited resistance (See [0030], [0036], [0050 and [0288]).
Regarding claims 18 and 94-95, Baker et al teach that the said microparticulate antimicrobial agents may be used to suppress microbial growth, reduce microbial infestation, reduce biofilm, inhibit microbial infection, inhibition of viral infection by herpes family viruses such as cytomegalovirus, herpes simplex viruses, etc, and/or infection by other viruses, including viruses causing viral infections including influenza viruses, severe acute respiratory virus (SARS), human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), etc, (See [0121]).
Regarding claims 94-95, it is noted that while Baker et al do not expressly disclose wherein the infection producing a superantigen, it is disclosed that the condition is Epstein-Barr virus. Infection by the Epstein–Barr virus, is known to cause production of a SAg in infected cells (Wikipedia).
Regarding claim 23, Baker et al teach that at least one of the synergizing antibiotic or the cooperative antimicrobial efficacy enhancing antibiotic comprises an antibiotic that is selected from an aminoglycoside antibiotic, a carbapenem antibiotic, a cephalosporin antibiotic, a fluoroquinolone antibiotic, a glycopeptide antibiotic, a lincosamide antibiotic, a penicillinase-resistant penicillin antibiotic, and an aminopenicillin antibiotic, etc, (See [0039]).
Regarding claims 26-29, Baker et al teach a method of preparing BisEDT and state that the obtain BisEDT is a yellow amorphous powdered solid and contained a single peak reflecting chemical purity of 100±0.1% (See [0111] and [0251]-[0252]).
Baker et al lack a specific disclosure on the patient having chronic inflammatory or managing or lessening the severity of cytokine storm, or elevated neutrophils. These are taught by Saha et al.
Saha et al teach a method for the treatment of a disease or disorder related to an inflammatory condition comprising administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising a metal and a thiol. In particular, inflammatory conditions that are associated with elevated levels of free TNFα. Said inflammatory conditions include arthritis, rheumatoid arthritis, asthma, psoriasis, systemic lupus erythematosus, inflammatory bowel syndrome, chronic obstructive respiratory diseases (COPD), etc, (See abstract).
The said metal-thiol comprises bismuth chelated by a thiol compound. Bismuth-ethanedithiol (BisEDT) is particularly preferred (See 0025]).
Regarding claims 88-91, Saha et al teach that metal-thiol compounds, preferably BisEDT are effective in treating inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel syndrome, etc, (See [0006], [0009], [0011], claims 5 and 9).
Regarding claims 100-101, Saha et al teach that methods of treating inflammatory conditions that are associated with elevated levels of free TNFα. The said diseases or disorders related to an inflammatory condition including one or more of the following inflammation related diseases/disorders: arthritis, rheumatoid arthritis, asthma, psoriasis, systemic lupus erythematosus, etc, (See [0011]). It is disclosed that cytokines are proteins naturally produced by immune cells and trigger responses to toxins, allergens, injury and microbial pathogens. Malfunction of these proteins can result in tissue damage and disease. The pathology underlying chronic inflammatory disease is the over-activation of pro-inflammatory cytokines such as TNF-α, Interleukin-1 (IL-1), IL-6, and IL-8 (See [0003] and [0039]).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Saha et al with that of Baker et al to arrive at the instant invention. It would have been obvious to do so because both references teach a method of treating one or more conditions by administration of a composition comprising a BT compound, preferably BisEDT. Specifically, Baker et al teach methods of treating viral respiratory infections by administration of a composition, in liquid droplet form to the subject via inhalation using an aerosol device. Baker et al also teach that the said compositions may comprise a synergistic antibiotic agent and wherein conditions such as bacterial or fungal infections or inflammation are treated as well. Infectious conditions disclosed by Baker et al include SARS, Epstein-Barr infections, HIV, etc. Saha et al also teach compositions comprising BisEDT and other active agents including antibiotics that are effectively treating chronic inflammatory conditions such as rheumatoid arthritis. Saha et al also disclose the relationship between infections and elevated levels of cytokine such as TNFα.
Thus, one of ordinary skill in the art is more than motivated to have combined the teachings of Saha et al with that of Baker et al to arrive at the claimed invention because from both references, one of ordinary skill in the art would have recognized that the combination of BisEDT with an antibiotic or anti-inflammatory agent would result in effective treatment of multiple conditions including viral and microbial respiratory infections and chronic inflammatory conditions that are in some way related to an infection.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Claims 1, 18-19, 23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Baker et al (US 20160375034) in view of Morse et al (Learning from the past: Possible urgent prevention and treatment options for sever acute respiratory infections caused by 2019-nCov).
Baker et al’s teachings are delineated above and incorporated herein.
Specifically, Baker et al disclose a method of treating biofilm production of natural surfaces such as respiratory tract with an unexpected synergy or enhancing effects between bismuth-thiol (BT) compounds and certain antibiotics. Baker et al also disclose that the said method can treat infections including SARS.
However, Baker et al do not expressly disclose combining BT with remdesivir or that the combination can treat SARS-CoV-1 or SARS-CoV-2. These are known in the art as taught by Morse et al.
Regarding claims 18-19, 23 and 25, Morse et al teach that 2019-nCoV virus shows strong homology with its better-studied cousin, SARS-CoV. Thus, four potential drug candidates (an ACE2-based peptide, remdesivir, 3CLpro-1 and a novel vinylsulfone protease inhibitor) are being suggested that could be used to treat patients suffering with the 2019-nCoV (See abstract).
Morse et al teach that remdesivir (GS-5734) displayed potent efficacy against SARS and MERS in human airway epithelial (HAE) cell models and in mice (IC50=0.069 and 0.074 μm for SARS-CoV and MERS-CoV, respectively, in HAE). Broad-spectrum activity against various bat coronaviruses was also demonstrated. (See page, 734, 1st col.).
Morse et al disclose structure of compounds inhibiting SARS-CoV viral replication through the mechanistic action of RdRp. The most promising candidate is remdesivir (See page 733, Figure 4).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Morse et al with that of Baker et al to arrive at the instant invention. It would have been obvious to do so because Baker et al teach methods of treating viral respiratory infections by administration of a composition, in liquid droplet form to the subject via inhalation using an aerosol device. Baker et al also teach that the said compositions may comprise a synergistic antibiotic agent and wherein conditions such as bacterial or fungal infections are treated as well. Infectious conditions disclosed by Baker et al include SARS, Epstein-Barr infections, HIV, etc. Morse et al also teach a method of effectively treating SARS-CoV and 2019-nCov with active agents including remdesivir. Morse et al teach that in their studies, it was discovered that the most promising candidate in inhibiting SARS-CoV viral replication is remdesivir.
Thus, one of ordinary skill in the art is more than motivated to have combined the teachings of Morse et al with that of Baker et al to arrive at the claimed invention because from both references, one of ordinary skill in the art would have recognized that the combination of BisEDT with remdesivir would result in effective treatment of viral respiratory infections including SARS-CoV.
From the combined teaching of the cited references, one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
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 1-3, 7, 10-11, 13, 18, 19, 23, 25-29, 85, 88-95 and 100-101 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,464,749 in view of Baker et al (US 20160375034), Saha et al (US 20110092589) and Morse et al (Learning from the past: Possible urgent prevention and treatment options for sever acute respiratory infections caused by 2019-nCov).
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Saha et al and Morse et al.
Examined claim 1 is directed to a method of treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises BisEDT suspended therein, wherein administering the BT composition is via inhalation, orally or nasally, using an aerosol device. Claim 2 recites the particle size range.
Reference claim 1 is directed to a method of treating, managing or lessening the severity of cystic fibrosis (CF) symptoms and infections in a subject, the method comprising administering to the subject an aerosol comprising a plurality of dispersed liquid droplets, wherein the liquid droplets comprise a bismuth-thiol (BT) composition that comprises bismuth-1,2-ethanedithiol (BisEDT) microparticles suspended therein, the BisEDT microparticles having a D90 of less than about 2 μm as measured by laser diffraction, and wherein at least 70% of the liquid droplets have a mass median aerodynamic diameter (MMAD) from about 0.4 μm to about 5 μm as measured by cascade impaction or laser time of flight.
The difference is that examined claims recite a method of treating or managing or lessening the severity of symptoms associated with a viral respiratory infection, while the reference claims disclose this method for cystic fibrosis or infection. However as disclosed by Baker et al compositions comprising a BT compound such as BisEDT are known to treat or manage symptoms of a viral infection on natural surfaces including respiratory tract. Reference claims also do not recite treating SARS, the secondary infection producing superantigens, treating cytokine storm and do not recite adding remdesivir. However, these are known in the art as taught by Saha et al and Morse et al and it would have been obvious to one of ordinary skill in the art to have incorporated them into the examined claims with a reasonable expectation of success.
Claims 1-3, 7, 10-11, 13, 18, 19, 23, 25-29, 85, 88-95 and 100-101 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 9-13 of U.S. Patent No. 9,028,878 in view of Baker et al (US 20160375034), Saha et al (US 20110092589) and Morse et al (Learning from the past: Possible urgent prevention and treatment options for sever acute respiratory infections caused by 2019-nCov).
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Saha et al and Morse et al.
Examined claim 1 is directed to a method of treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises BisEDT suspended therein, wherein administering the BT composition is via inhalation, orally or nasally, using an aerosol device. Claim 2 recites the particle size range.
Reference claim 1 is directed to a method for protecting a natural surface against one or more of a bacterial pathogen, a fungal pathogen and a viral pathogen, comprising: contacting the surface with an effective amount of a BT composition under conditions and for a time sufficient for one or more of:
(i) prevention of infection of the surface by the bacterial, fungal or viral pathogen,
(ii) inhibition of cell viability or cell growth of substantially all planktonic cells of the bacterial, fungal or viral pathogen,
(iii) inhibition of biofilm formation by the bacterial, fungal or viral pathogen, and
(iv) inhibition of biofilm viability or biofilm growth of substantially all biofilm-form cells of the bacterial, fungal or viral pathogen,
wherein the BT composition comprises a plurality of solid microparticles that exhibit a unimodal size distribution when the BT composition is analyzed on a particle size analyzer and that comprise a bismuth-thiol (BT) compound that has not been micronized, milled or subjected to super-critical fluid processing, substantially all of said microparticles having a volumetric mean diameter of from about 0.4 μm to about 5 μm, wherein the BT compound comprises bismuth or a bismuth salt and a thiol-containing compound and the BT composition comprises at least one antibiotic compound that is capable of acting synergistically with, or enhancing, the BT compound, wherein the antibiotic compound comprises an antibiotic that is selected from methicillin, vancomycin, nafcillin, gentamicin, ampicillin, chloramphenicol, doxycycline, clindamycin, gatifloxacin, cefazolin and an aminoglycoside antibiotic, and wherein the aminoglycoside antibiotic is selected from the group consisting of amikacin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, rhodostreptomycin, streptomycin, and apramycin.
The difference is that examined claims recite a method of treating or managing or lessening the severity of symptoms associated with a viral respiratory infection via inhalation using an aerosol, while the reference claims disclose this method wherein the composition can be administered by inhalation or nasally, but there is no recitation of an aerosol. However as disclosed by Baker et al compositions comprising a BT compound such as BisEDT are known to treat or manage symptoms of a viral infection on natural surfaces including respiratory tract wherein the inhalation is achieved by an aerosol device. Reference claims also do not recite treating SARS, the secondary infection producing superantigens, treating cytokine storm and do not recite adding remdesivir. However, these are known in the art as taught by Saha et al and Morse et al and it would have been obvious to one of ordinary skill in the art to have incorporated them into the examined claims with a reasonable expectation of success.
Claims 1-3, 7, 10-11, 13, 18, 19, 23, 25-29, 85, 88-95 and 100-101 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-24 of U.S. Patent No. 10,960,012 in view of Baker et al (US 20160375034), Saha et al (US 20110092589) and Morse et al (Learning from the past: Possible urgent prevention and treatment options for sever acute respiratory infections caused by 2019-nCov).
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Saha et al and Morse et al.
Examined claim 1 is directed to a method of treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises BisEDT suspended therein, wherein administering the BT composition is via inhalation, orally or nasally, using an aerosol device. Claim 2 recites the particle size range.
Reference claim 14 is directed to a method for protecting a natural surface against one or more of a bacterial pathogen, a fungal pathogen and a viral pathogen, comprising: contacting the surface with an effective amount of the BT composition of claim 1 under conditions and for a time sufficient for one or more of:
(i) treatment of infection of the surface by the bacterial, fungal or viral pathogen,
(ii) inhibition of cell viability or cell growth of substantially all planktonic cells of the bacterial, fungal or viral pathogen,
(iii) inhibition of biofilm formation by the bacterial, fungal or viral pathogen, and
(iv) inhibition of biofilm viability or biofilm growth of substantially all biofilm-form cells of the bacterial, fungal or viral pathogen.
Composition of claim 1 is a bismuth-thiol composition, comprising a plurality of solid microparticles that comprise a bismuth-thiol (BT) compound, substantially all of said microparticles having a volumetric mean diameter of from 0.4 μm to 5 μm, wherein the BT compound comprises bismuth or a bismuth salt in association with 1,2-ethane dithiol. Claim 13 is directed to the said composition being a liquid suspension. In claim 16, the epithelial tissue surface is respiratory tract.
The difference is that examined claims recite a method of treating or managing or lessening the severity of symptoms associated with a viral respiratory infection via inhalation using an aerosol, while the reference claims disclose this method wherein the composition can be administered by inhalation or nasally, but there is no recitation of an aerosol. However as disclosed by Baker et al compositions comprising a BT compound such as BisEDT are known to treat or manage symptoms of a viral infection on natural surfaces including respiratory tract wherein the inhalation is achieved by an aerosol device. Reference claims also do not recite treating SARS, the secondary infection producing superantigens, treating cytokine storm and do not recite adding remdesivir. However, these are known in the art as taught by Saha et al and Morse et al and it would have been obvious to one of ordinary skill in the art to have incorporated them into the examined claims with a reasonable expectation of success.
Claims 1-3, 7, 10-11, 13, 18, 19, 23, 25-29, 85, 88-95 and 100-101 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-26 of U.S. Patent No. 8,389,021 in view of Baker et al (US 20160375034), Saha et al (US 20110092589) and Morse et al (Learning from the past: Possible urgent prevention and treatment options for sever acute respiratory infections caused by 2019-nCov).
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Saha et al and Morse et al.
Examined claim 1 is directed to a method of treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises BisEDT suspended therein, wherein administering the BT composition is via inhalation, orally or nasally, using an aerosol device. Claim 2 recites the particle size range.
Reference claim 13 is directed to a method for protecting an epithelial tissue surface against a bacterial pathogen, comprising: contacting the epithelial tissue surface with an effective amount of a BT composition of claim 1, under conditions and for a time sufficient for one or more of:
(i)prevention of infection of the epithelial tissue surface by the bacterial pathogen,
(ii) inhibition of cell viability or cell growth of substantially all planktonic cells of the bacterial pathogen,
(iii) inhibition of biofilm formation by the bacterial pathogen, and
(iv) inhibition of biofilm viability or biofilm growth of substantially all biofilm-form cells of the bacterial pathogen.
Composition of claim 1 is a bismuth-thiol composition, comprising: a plurality of solid microparticles that exhibit a unimodal size distribution when the composition is analyzed on a particle size analyzer and that comprise a bismuth-thiol (BT) compound that has not been micronized, milled or subjected to super-critical fluid processing, substantially all of said microparticles having a volumetric mean diameter of from about 0.4 μm to about 5 μm, wherein the BT compound comprises bismuth or a bismuth salt and a thiol-containing compound. In claim 17, the epithelial tissue surface is respiratory tract.
The difference is that examined claims recite a method of treating or managing or lessening the severity of symptoms associated with a viral respiratory infection via inhalation using an aerosol, while the reference claims disclose a method for protecting epithelial surfaces against bacterial or fungal infections and do not recite administration via an aerosol. However, as Baker et al teach, it is known that compositions comprising a BT compound such as BisEDT can treat or manage symptoms of a viral infection on natural surfaces including respiratory tract wherein the inhalation is achieved by an aerosol device. Reference claims also do not recite treating SARS, the secondary infection producing superantigens, treating cytokine storm and do not recite adding remdesivir. However, these are known in the art as taught by Saha et al and Morse et al and it would have been obvious to one of ordinary skill in the art to have incorporated them into the examined claims with a reasonable expectation of success.
Claims 1-3, 7, 10-11, 13, 18, 19, 23, 25-29, 85, 88-95 and 100-101 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-30 of U.S. Patent No. 10,835,510 in view of Baker et al (US 20160375034), Saha et al (US 20110092589) and Morse et al (Learning from the past: Possible urgent prevention and treatment options for sever acute respiratory infections caused by 2019-nCov).
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Saha et al and Morse et al.
Examined claim 1 is directed to a method of treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises BisEDT suspended therein, wherein administering the BT composition is via inhalation, orally or nasally, using an aerosol device. Claim 2 recites the particle size range.
Reference claim 20 is directed to a method of treating a wound, comprising administering to a subject the composition of claim 1. Claim 22 is directed to a method of treating bacterial infection. Reference claim 24 is directed to method of treating an acute wound, a chronic wound or a wound of epithelial tissue surface that contains microbial biofilm in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a topical formulation that comprises the BT composition of claim 1, wherein the composition is applied to the surface of the infection.
Composition of claim 1 is a bismuth-thiol (BT) composition, comprising a plurality of solid microparticles and a pharmaceutically acceptable carrier, wherein substantially all of said microparticles having a volumetric mean diameter (VMD) of from about 0.4 μm to about 5 μm, said microparticles comprising a BT compound comprising bismuth and/or a bismuth salt, and wherein the composition does not include a liposome. Claim 18 recites that the composition is a liquid suspension and claim 19 delivers the composition via an aerosol.
The difference is that examined claims recite a method of treating or managing or lessening the severity of symptoms associated with a viral respiratory infection via inhalation using an aerosol, while the reference claims disclose a method for treating or inhibiting bacterial infection on a surface. However, as Baker et al teach, it is known that compositions comprising a BT compound such as BisEDT can treat or manage symptoms of a viral infection on natural surfaces including respiratory tract wherein the inhalation is achieved by an aerosol device. Reference claims also do not recite treating SARS, the secondary infection producing superantigens, treating cytokine storm and do not recite adding remdesivir. However, these are known in the art as taught by Saha et al and Morse et al and it would have been obvious to one of ordinary skill in the art to have incorporated them into the examined claims with a reasonable expectation of success.
Claims 1-3, 7, 10-11, 13, 18, 19, 23, 25-29, 85, 88-95 and 100-101 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Nos. 12,036,200; 9,408,393; 11,207,288 and 11,974,978 in view of Baker et al (US 20160375034), Saha et al (US 20110092589) and Morse et al (Learning from the past: Possible urgent prevention and treatment options for sever acute respiratory infections caused by 2019-nCov).
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Saha et al and Morse et al.
Examined claim 1 is directed to a method of treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises BisEDT suspended therein, wherein administering the BT composition is via inhalation, orally or nasally, using an aerosol device. Claim 2 recites the particle size range.
Reference claims are directed to similar methods of treating, managing or lessening the symptoms of an infection on a natural surface. Similar to the rejections described above, the claims are not patentably distinct.
Due to the number of reference patents the rejections had to be made collectively.
Claims 1-2, 26-30 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 28 and 54 of copending Application No. 18/273,841 (US 20250002514) in view of Baker et al (US 20160375034).
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims in view of Baker et al, Saha et al and Morse et al.
Examined claim 1 is directed to a method of treating, managing or lessening the severity of symptoms associated with a respiratory viral infection in a subject, the method comprising administering to the subject a bismuth-thiol (BT) composition that comprises BisEDT suspended therein, wherein administering the BT composition is via inhalation, orally or nasally, using an aerosol device. Claim 2 recites the particle size range. Examined claims 26-30 are directed to the compound BisEDT of claim 1 being amorphous and claims 27-30 recites specifics of the said amorphous compound.
Reference claims 1-5 are directed to an amorphous form of BisEDT and its specifics. Reference claims 28 and 54 are directed to a method of treating or managing the severity of symptoms of CF or infection in a subject by administering to the subject via inhalation the composition of claim 41 (comprising liquid droplets comprising BisEDT of claim 1).
With regard to examined claims 26-30, the difference is that reference claims 1-5 do not contain the limitations of the method. However, the said amorphous BisEDT is incorporated in the method claims. The difference between examined claims 1-2 and 85 and reference claims 28 and 54 is that reference claims do not recite treating a viral infection. However, as Baker et al teach, it is known that compositions comprising a BT compound such as BisEDT can treat or manage symptoms of a viral infection on natural surfaces including respiratory tract wherein the inhalation is achieved by an aerosol device. Thus, it would have been obvious to one of ordinary skill in the art to have incorporated the teachings of Baker et al into the examined claims with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 7, 10-11, 13, 18, 19, 23, 25-30, 85, 88-95 and 100-101 are rejected. Claims 34, 41, 46 and 55 are withdrawn.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
1 As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.