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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/16/26 has been entered.
Receipt is acknowledged of Amendments and Remarks filed on 01/16/26 and an IDS filed on 02/10/26. Claims 1-2 have been amended, no new claims have been added and no claims have been canceled. Accordingly, claims 1-2, 7-11, 15-18, 20-22, 24-27, 29 and 32-33 remain pending and under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
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 1-2, 7-11, 15-18, 20-22, 24-27, 29 and 32-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Independent claims 1 and 2 have been amended to include “the daily dosage delivered to the bronchial tree is about 300 µg/ml silver nanoparticles”. The Specification does not provide support for this limitation.
In some preferred embodiments, the concentration of silver nanoparticles in the suspension is from 0.01 to 200 μg/ml. In some preferred embodiments, the concentration of silver nanoparticles in the suspension is from 0.1 to 100 μg/ml.
(See [0009]-[0010], [0015] and [0046]-[0047] of the published Spec).
The only reference to a 300 μg is in paragraph [0124] which states:
It is further preferred to nebulize 3 doses AgNPs per day, over a 10-14 day course, for antiviral therapy, as in typical antibiotics inhalation treatment plans. This amounts to daily inhalation of about 300 μg of AgNPs, for 10-14 consecutive days.
Thus, the Specification fails to support a daily dosage of 300 μg/ml.
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 1-2, 7-11, 15-18, 20-22, 24-27, 29 and 32-33 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 are indefinite for including a limitation of a daily dosage of about 300 µg/ml. This renders the claims indefinite because about 300 µg/ml is a concentration measure and not a daily dosage. It is not clear how many milliliters of this composition is delivered and how often in a given day.
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.
Applicant’s claims
Claims 1 and 2 are directed to a method for treating or inhibiting or prophylaxis of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a human or animal subject, the method comprising: administering silver nanoparticles via inhalation in an effective concentration to the subject under conditions such that infection by SARS-CoV-2 is inhibited or treated, wherein the daily dosage delivered to the bronchial tree is about 300 µg/ml silver nanoparticles.
Claim interpretation:
Claim 33 is a product-by-process claim. The process of reducing silver nitrate salt with tannic acid does not materially affect the claimed method and is not given patentable weight.
Claims 1-2, 7-11, 15-18, 20-22, 24, 26-27, 29 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Tarbet et al (US 20180078580) in combination with Zachar et al (Formulations for COVID-19 treatment via silver nanoparticles inhalation delivery).
Tarbet et al teach stabilized multi-component antimicrobial compositions for treating tissue diseases, infections or conditions including a first and second set of differently sized and/or differently shaped metal nanoparticles, and a stabilizing agent. for treatment of diseases, infections or conditions caused by microbial infections, such as bacteria, viral, and/or fungal infections, or for preventing the infection (See abstract and claim 3).
The said metal nanoparticles can comprise spherical-shaped metal nanoparticles comprising silver (See [0014]-[0016] and [0049]). The said spherical-shaped metal nanoparticles are highly resistant to ionization, highly stable, and highly resistance to agglomeration, and can have a diameter of about 40 nm or less, about 15 nm or less, about 10 nm or less, about 7.5 nm or less, or about 5 nm or less (See [0042]-[0043]).
In the case of viruses, spherical-shaped and coral-shaped metal nanoparticles can alternatively deactivate viruses by attaching to glycoproteins and/or catalyzing protein denaturing reactions in the protein coat so that the virus is no longer able to attach to a host cell and/or inject genetic material into the host cell. Because very small nanoparticles can pass through a virus, denaturing of the protein coat may occur within the interior of the virus. A virus that is rendered unable to attach to a host cell and/or inject genetic material into the host cell is essentially inactive and no longer pathogenic (See [0053]).
Tarbet et al state that “in the particular case of silver (Ag) nanoparticles, the interaction of the silver (Ag) nanoparticle(s) within a microbe has been demonstrated to be particularly lethal without the need to rely on the production of silver ions (Ag+) to provide the desired antimicrobial effects, as is typically the case with conventional colloidal silver compositions. The ability of silver (Ag) nanoparticles to provide effective microbial control without any significant release of toxic silver ions (Ag+) into the surrounding environment is a substantial advancement in the art” (See [0056]).
It is also stated that anti-viral compositions comprise metal nanoparticles having a particle size of about 8 nm or less (See [0057]).
Exemplary carriers for nasal or pulmonary aerosol or inhalation administration include solutions in saline and a stabilizing agent such as a polysaccharide. In some embodiments, the nanoparticles and additional stabilizing agents and/or carriers are formulated as dry powders (e.g., powders useful for administering with dry powder inhalers) (See [0082]).
Exemplary aerosols useful for nasal and/or inhalation administration can include a vaporizable propellant. Ingredients such as water, alcohol, propylene glycol, and polyethylene glycols can be additionally included. Other embodiments, also useful for nasal and/or inhalation administration, may be provided as sprays (e.g., omitting an aerosol propellant). Such spray formulation may be provided as a solution or suspension capable of forming a fine mist for administration, and in some embodiments, may include saline and/or be isotonic (See [0083]).
Tarbet et al teach a method of treating or prophylactically treating a viral infection in a subject via inhalation of a composition comprising silver nanoparticles and wherein the infection is a respiratory infection. However, Tarbet et al’s disclosure is silent with regard to the respiratory viruses and the effective amount of silver nanoparticles in µg/mL or delivery by continuous nebulization. These are known in the art as taught by Zachar et al.
Zachar et al teach formulations for COVID-19 treatment via silver nanoparticles inhalation delivery. It is disclosed that for suppression of both viral and bacterial respiratory infections, we present candidate formulations and treatment protocols based on nano-silver colloids (NAgC) by inhalation delivery. Special evaluation is given to Corona virus. The said treatment formulations may be most effectively applied as a first-line intervention at an early stage of respiratory infections, i.e., when mostly affecting the upper respiratory system and bronchial tree (See Abstract Objectives).
Zachar et al disclose that the dosage is highly sensitive to the silver nanoparticle size, with 3-7 nm being the optimal size. Effective anti-viral inhibitory concentration (IC) of 10μg/ml is estimated as a reasonable target concentration to achieve in the mucus fluid of the respiratory system. With colloidal silver of 5 nm particles, delivering inhalation of standard 5μ diameter droplets aerosol (e.g., using off-the-shelf ultrasonic mesh nebulizers), we assert that IC can be achieved with depositing a total of just 0.33 cc of a 30 μg/ml NAgC concentration in the bronchial tree. Yet, after accounting for effective deposition fraction (~30%) and due to the fact that active inhalation time is just about 1/3 of the breathing cycle (if common continuous nebulizers are used, rather than breath-activated), a dosage of 3.3 ml needs to be continuously nebulized for inhalation by the user. We recommend that exhalation through the nose can be implemented as a method to deliver the exhaled fraction of NAgC also to the nasal cavity when the nebulized inhalation is done orally (See paragraph bridging pages 1-2).
Zachar et al conclude that IC concentrations of such colloids is about 10 µg/ml (table-1). In particular, for lung infections treatment by inhalation delivery (table-1), a minimal IC would require silver nanoparticle treatment deposition of 11 μg which come about from inhalation of about 33 μg of silver aerosol (since only about 30% of inhalation get deposited). If treatment is performed 3 times daily, it translates into daily deposition of about 33 μg and aerosol inhalation of 100 μg. We assume a recommended 3xIC dosage, amounting to daily deposition of about 100 μg and aerosol inhalation of 300 μg, taken over a 5 days period. “Available safety information indicates that such dosages and regimen are well within safe range. We estimate that these formulations can be effective for prevention and treatment of any respiratory viral infections at early stages, including COVID-19 / SARS-CoV-2 (See Discussion on page 14).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teachings of Zachar et al with that of Tarbet et al to arrive at the claimed invention. It would have been obvious to do so because Tarbet et al teach effective treatment of viral infections by administration of compositions comprising silver nanoparticles including by nasal or pulmonary inhalation to the subject’s respiratory system. Tarbet et al provide sufficient teachings to one of ordinary skill in the art to select the effective particle size for effective delivery of the silver nanoparticles to inactivate the viruses and prevent the further development of a viral infection at the site. Similarly, Zachar et al teach effective treatment of a respiratory viral infection such as by COVID-19 (SARS) by inhalation of a composition comprising silver nanoparticles. Both references teach one of ordinary skill in the art on the specifics of this method to effectively make and use the said compositions and deliver them to the target site, i.e. respiratory system, by inhalation for effective treatment and eradication of a respiratory viral infection.
Regarding the presence of a thixotropic agent, polyethylene glycol disclosed by Tarbet et al is considered a rheology/thixotropic agent. Regarding the starch, Tarbet et al teach the presence of polysaccharides. Regarding the daily dosage delivered to the bronchial tree is about 300 µg/ml silver nanoparticles, Zachar et al teach a dosage of 10 µg/mL which may be nebulized continuously for three minutes, i.e. 30 µg/mL. Zachar et al also recommend a daily deposition of inhaled 300 μg. Additionally, with regards to concentrations, the courts have held that the person of ordinary skill in the art is capable of optimizing the concentration ranges based on need or effectiveness. That is, optimization of ranges is obvious to one of ordinary skill in the art.
In other words, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
The claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 1-2, 7-11, 15-18, 20-22, 24-27, 29 and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Tarbet et al (US 20180078580) in combination with Zachar et al (Formulations for COVID-19 treatment via silver nanoparticles inhalation delivery) and Krasnow et al (US 20130315972).
The teachings of Tarbet et al and Zachar et al are delineated above and incorporated herein.
The combined references lack a specific disclosure on the surface plasmon peak of the said silver nanoparticles. This is known in the art as taught by Krasnow et al. Additionally, Krasnow et al discloses formulations comprising silica (a thixotropic agent) and starches which prevent agglomeration.
Krasnow et al teach compositions having antimicrobial activity containing particles comprising at least one inorganic copper salt; and at least one functionalizing agent in contact with the particles (See abstract). The said compositions additionally comprising at least one of silver particles or silver halide particle (See [0016], [0025], [0031] and claims 49-50).
It is disclosed that the said metal particles have a size range from 3 nm (See [0012] and [0046]) and formulations may comprise a functionalizing agent including starches. The said functionalizing agent stabilizes the particles in a carrier. Also, the said functionalizing agent stabilizing the particle in a carrier (in liquids) prevents agglomeration where particles are uniformly distributed (See [0014]-[0015], [0035], [0043]-[0044] and [0057]).
The term “stabilizing said particle in a carrier” means to maintain the functionalized particle dispersed and separate from other particles in the liquid carrier such that agglomeration and/or settling out of suspension is inhibited (See [0093]).
Krasnow et al teach that the carrier particles may contain silica such as ZeothixTM (See [0152]).
The aerosols can be prepared using a nebulizer and delivered to the patient's lungs to provide the desired high dose of antimicrobial activity, or administered via inhalation. In cases where deep penetration of the antimicrobial agent into the airways is desired, use of small nano-sized particles may be desirable (See claim 33 and [0212]).
In Example 26, Krasnow et al disclose preparation of AG particles and state that “The mixture was stirred at room temperature to form a clear yellow solution. To this solution was added 0.04926 g of silver nitrate 99.0% ACS reagent Sigma Aldrich Cat. #209139) and the solution heated to 70° C. for 7 hours while stirring. During this time the reaction was followed by PVP absorption with the formation of the Plasmon peak at 425 nm due to the reduction of silver nitrate to silver metal by PVP (See [0297]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teachings of Krasnow et al and Zachar et al with that of Tarbet et al to arrive at the claimed invention. The reasons for combining Zachar et al with Tarbet et al is disclosed above and incorporated herein.
Additionally, it would have been obvious to one of ordinary skill in the art to have combined the teachings of Krasnow et al with that of Tarbet et al and Zachar et al because Krasnow et al teach inhalable compositions comprising silver nanoparticles for their anti-viral effect and disclose effective compositions comprising starches, silica and other carriers and wherein the prepared silver nanoparticles have a peak plasmon of about 425 nm.
One of ordinary skill in the art would have been motivated to have combined the teachings of Krasnow et al into the methods and compositions of Tarbet et al and Zachar et al because effectively, all three references teach treating viral infections with a composition comprising silver nanoparticles and delivered to the pulmonary system. Krasnow et al provides guidance on the surface plasmon peak of said nanoparticles for optimum delivery and virus inactivation.
Thus, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Response to Arguments
Applicant's arguments filed 01/16/26 have been fully considered but they are not persuasive.
Applicant’s argument is that Zachar et al does not teach or suggest the claimed concentration range /dosage. Applicant argues that “As previously argued, Zacher extrapolates their dosages from HIV infection. The claimed daily dosage is again much higher (by a factor of 50%) than the dosage calculated by Zacher. This could not have been predicted based on the disclosure of Zacher or in combination with Tarbet or Krasnow. The data in Examples 6 and 7 of the instant application show that the extrapolation by Zachar was not correct and that a higher concentration of silver nanoparticles is required in the suspension to be effective. Applicant respectfully submits that the combined references do not teach each element of the claims as amended and that therefore there is no prima facie case of obviousness” (See Remarks, pages 6-7).
The above arguments are not found persuasive. Firstly, as rejected above, the Specification fails to support the newly added daily dosage amount of 300 µg/ml and the said amount is not a daily dosage but a concentration. Therefore, this limitation is not considered part of the claims. Secondly, Zachar et al’s disclosure is drawn to formulations for treating COVID-19 by silver nanoparticles and they disclose the dosage amount that is administered to the bronchial tree of a subject with COVID-19 infection. 3-Zachar disclose that inhibitory concentrations can be achieved with depositing a total of just 0.33cc of a 30 µg/ml NAgC concentration in the bronchial tree. It is also disclosed that a dosage of 3.3 ml needs to be continuously nebulized for inhalation by the user. Zachar et al also recommend a daily deposition of inhaled 300 μg. That is, considering all teachings of the references, especially Zachar et al, one of ordinary skill in the art is more than capable of optimization of ranges, as optimization of concentration ranges is well within the capabilities of one of ordinary skill in the art and is not considered an inventive step.
In this regard, the courts have held that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed.Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). See MPEP 2144.05.
Claims 1-2, 7-11, 15-18, 20-22, 24-27, 29 and 32-33 are rejected.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616