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 .
Detailed Action
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8 March 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner. See attached copy of PTO-1449.
Status of Application
2. The instant application is a national stage entry of PCT/EP2021/074624 filed 7 September 2021. Claims 1-2, 4-13, and 15 are currently pending. Claims 3 and 14 are cancelled. Claims 1-2, 4-13 and 15 are examined on the merits within.
Examiner’s Note: The specification defines preventing as “As used herein, "preventing" encompasses "reducing the likelihood of occurrence" and "reducing the likelihood of re-occurrence" and "delaying the likelihood of occurrence or re-occurrence". See page 12.
Claim Objections
3. Claim 4 is objected to because of the following informalities: “and their pharmaceutically acceptable salts” should instead recite “or their pharmaceutically acceptable salts”. Appropriate correction is required.
Claim Rejections – 35 U.S.C. 102
4. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
5. Claim(s) 13 and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stary et al. (U.S. Patent Application Publication No. 2020/0215179).
Regarding instant claims 13 and 15, Stary et al. disclose adjuvant loaded nanoparticles administered to a subjects mucosal membrane. See abstract. The polymer that forms the nanoparticle is a biodegradable polymer selected from polylactic acid, polyglycolic acid, or poly(lactic-co-glycolic acid). See paragraph [0095]. The composition can be aerosolized. See paragraph [0169].
Thus the instant claims are anticipated by Stary et al.
Claim Rejections – 35 U.S.C. 102/103
6. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
7. Claim(s) 1-2, 4-5, 9-10, and 12 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Perverzeva et al. (International Journal of Pharmaceutics, 2019).
Regarding instant claims 1-2, 4-5, and 9-10, Perverzeva et al. teach that hematological and cardiac toxicity of doxorubicin could be reduced by binding the drug to PLGA nanoparticles. See abstract. Table 6 shows that day 30 post treatment of DOX resulted in toxic cardiomyopathy. The nanoparticles have an average diameter of about 94 nm. See Section 3.1. The major dose-limiting toxicities of free doxorubicin are neutropenia as an acute toxicity and cardiomyopathy. As a result, treatment with doxorubicin or other anthracyclines frequently has to be discontinued, although patients are still responsive. Although anthracycline-related cardiotoxicity is generally evaluated using a “chronic model” that involves weekly administrations over periods of several months, sometimes with even longer observation periods, in the present, relatively short-term study it was possible to observe both, morphological and functional signs of cardiotoxicity that were clearly formulation-dependent. See Discussion. The drug release from a PLGA particle generally occurs first as a result of the drug desorption and diffusion from the surface and the polymeric core, and then at a later step due to degradation of the core. See Section 3.1. Thus the nanoparticle is not covalently bound to nor encapsulates an anthracycline or amino-4-quinoleine.
Regarding instant claim 12, Perverzeva et al. teach doxorubicin hydrochloride dissolved in HCl (second part) and a solution of PLGA (first part). See Section 2.1.
Thus the instant claims are anticipated by Perverzeva et al. and in the alternative it would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to administer doxorubicin with PLGA nanoparticles to reduce toxic cardiomyopathy and anthracycline toxicity in a patient because Perverzeva et al. teach the toxicity can be reduced by binding the drug to PLGA nanoparticles.
Claim Rejections – 35 U.S.C. 103
8. 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.
9. Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perverzeva et al. (International Journal of Pharmaceutics, 2019) as applied to claims 1-2, 4-5, 9-10, and 12 above and further in view of Sabato et al. (Journal of Pharmacy Practice, 2016).
Perverzeva et al. do not teach hydroxychloroquine.
Sabato et al. teach that hydroxychloroquine administration causes the adverse effect of cardiomyopathy. See abstract.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to administer PLGA particles with hydroxychloroquine to treat the adverse effect of cardiomyopathy because Perverzeva et al. teach cardiac toxicity of doxorubicin could be reduced by binding the drug to PLGA nanoparticles. Thus there would be a reasonable expectation of success of reducing adverse effects of hydroxychloroquine administration similarly to doxorubicin since the ailment is caused by the drug administered.
10. Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perverzeva et al. (International Journal of Pharmaceutics, 2019) as applied to claims 1-2, 4-5, 9-10, and 12 above and further in view of Wang et al. (Journal of Photochemistry & Photobiology, 2019).
Perverzeva et al. do not teach silica.
Wang et al. teach that polymeric nanoparticles improve biocompatibility of ineffectively retained medications, broaden habitation time in the body and give a continued medication discharge display. The most generally utilized polymer for assembling polymeric nanoparticles is PLGA. See page 2, paragraph 2. PLGA layers are assembled onto superparamagnetic SiN for controlling medication discharge profile. See page 2, paragraph 3. The nanoparticles allow for the controlled arrival of the flavonoid quercetin to secure against cardiovascular maladies. See abstract. Cardiovascular illnesses include cardiomyopathy. See page 1, paragraph 1.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to add silica to the particles of Perverzeva et al. to control the arrival of the active agent. One would have been motivated, with a reasonable expectation of success, to secure against cardiovascular maladies as taught by Wang et al.
11. Claim(s) 8 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Perverzeva et al. (International Journal of Pharmaceutics, 2019) as applied to claims 1-2, 4-5, 9-10, and 12 above and further in view of Youngs et al. (U.S. Patent Application Publication No. 2010/0210616).
Perverzeva et al. do not teach a diameter of less than 50 nm or aerosolization.
Youngs et al. teach incorporation of a metal complex into a polymeric nanoparticle. See abstract. The therapeutic agent is dissolved, encapsulated, entrapped or chemically conjugated to the nanoparticle matrix. The biodegradable polymeric nanoparticles include polyglycolic acid, polylactic acid, or poly(lactic-co-glycolic) acid. See paragraph [0049]. Aerosol inhalation via a method like nebulization provides an easy and a non-invasive route to accomplish that objective. See paragraph [0047]. Nanoparticles vary in size from 10 to 1000 nm. See paragraph [0048]. Nanoparticles, including nanospheres, unlike microspheres, can be used to directly target the tissues via systemic circulation or across the mucosal membrane. This targeting is possible as a result of the capacity of these nanoparticles to be endocytosed by individual cells. See paragraph [0048].
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to formulate the composition as an aerosol to provide an easy and non-invasive route of administration. One would have been motivated, with a reasonable expectation of success, because Youngs et al. teach effective administration of PLGA nanoparticles via a nebulizer. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to reduce the size of the nanoparticles to less than 50 nm because Youngs et al. teach that biodegradable nanoparticles, including PLGA, with therapeutic agents, can be effectively administered in sizes of 10 to 1000 nm.
Conclusion
12. No claims are allowed at this time.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615