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 .
Priority
This application is a national phase entry pursuant to 35 U.S.C. § 371 of International Application No. PCT/US2021/022089, filed March 12, 2021, which claims priority to U.S. Provisional Application No. 63/002,165, filed on March 30, 2020, and U.S. Provisional Application No. 63/122,858, filed on December 8, 2020.
Claims Status
Claims 2, 3, and 9 are canceled. Claims 1, 4-8, and 10-23 are pending and under examination.
Claim Objections
Claims 1 and 8 are objected to because of the following informalities: the recitation of pulmonary inflammatory disease can infer more than one disease. In light of the specification and claim 18, the pulmonary inflammatory disease claimed appears to be a single pulmonary inflammation disease. Therefore, the claim should recite a pulmonary inflammation disease. The term “about 50 to about 100 µg” should be “about 50 µg to about 100 µg for consistency purpose.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 and 8 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. The term “about” in the claims 8 which is taken by the Examiner to further define the therapeutically effective amount recited in claim 1, renders the claim indefinite, because it is not clearly what the metes and bounds of about. Specifically, the specification teaches as used herein, the term "about" refers to a value or composition that is within an acceptable error range for the particular value or composition as determined by one of ordinary skill in the art, which will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, "about" or "approximately" can mean within one or more than one standard deviation per the practice in the art. Alternatively, "about" or "approximately" can mean a range of up to 10% (i.e., ±10%) or more depending on the limitations of the measurement system. A range of 10% (i.e., ±10%) or more can include up to 50, up to 70, etc.… If one uses the meaning of 10% (i.e., ±10%) or more for the claimed language about 0.1 μg to about 100 μg, or wherein the dose of RTX ranges from about 0.1 μg to about 1 μg, about 1 μg to about 5 μg, about 5 μg to about 10 μg, about 10 μg, to about 20 μg, about 20 μg to about 50 μg, or about 50 to about 100 ug. The specification does not provide a stander for ascertain the requisite degree, and one of ordinary skill in the art would not reasonably apprise of the scope of the claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 4-8, 11-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (US2019/0076396 A1) in view of Tsuji et al (. 2012 Aug 17;5(8):837–852) and Malaviya et al (Pharmacol Ther. 2017 Jun 19; 180:90–98).
Jones teaches a non-alcoholic formulation of resiniferatoxin (RTX) for intrathecal, intraarticular, intraganglionic or periganglionic administration comprising from about 10 μg/mL to about 200 μg/mL RTX in a formulation having enough monosaccharide to keep the specific gravity between 1.0 and 1.3 and can be solubilized in a mixture, of PEG (0-40%), polysorbate (0-5%) and cyclodextrin (0-5%) in an aqueous buffer solution with saline and a pH from about 6.5 to about 7.5 and containing an antioxidant. (See paragraph [0007].) Intraganglionic administration” is administration to within a ganglion. Jones teaches intraganglionic administration can be achieved by direct injection into the ganglion and also includes selective nerve root injections, or periganglionic administration, in which the compound passes up the connective tissue sleeve around the nerve and enters the ganglion from the nerve root just outside the vertebral column. (See paragraph [0009].) Nerve root injection is a species of nerve block. Jones also teaches the aqueous buffer with saline can be considered a pharmaceutically acceptable carrier that includes water and saline. The formulation Preferably comprises from about 25-50 μg/mL RTX. (See paragraph [0008].) Moreover, Jones teaches RTX is a known transient receptor potential cation channel subfamily V member 1 (TrpV1) agonist. (See paragraph [0004].) Jones further teaches activation of TrpV1 typically occurs at the nerve endings via application of painful heat and is up-regulated during certain types of inflammatory stimuli. (See paragraph [0003].) Lastly, Jones teaches for intraganglionic administration, a typical volume injected is from 50 to 300 microliters delivering a total amount of RTX that ranges from about 50 nanograms (0.5 μg) to about 50 micrograms. Often the amount administered is from 200 ng (0.2 μg) to 10 μg. RTX can be administered as a bolus or infused over a period of time, typically from 1 to 10 minutes. 0.5 μg to 50 μg reads on claim 8.
Jones does not teach treating pulmonary inflammatory disease that includes inflammation associated with mechanical ventilation, acute respiratory distress syndrome (ARSD) and chronic obstructive pulmonary disease (COPD).
Tsuji teaches SA13353 (1-[2-(1-adamantyl) ethyl]-1-pentyl-3-[3-(4-pyridyl) propyl] urea), a novel TRPV1 agonist, inhibits tumor necrosis factor-alpha (TNF-α) production by the activation of capsaicin-sensitive afferent neurons and reduces the severity of symptoms in kidney injury, lung inflammation, arthritis, and encephalomyelitis has been demonstrated. These results suggest that TRPV1 agonists may act as anti-inflammatories in certain inflammatory and autoimmune conditions in vivo. (See Abstract.) Tsuji also teaches TRPV1 agonists capsaicin, resiniferatoxin, and SA13353 (1- [2-(1- adamantyl) ethyl]-1-pentyl-3-[3-(4-pyridyl) propyl] urea) attenuate renal tumor necrosis factor (TNF)-[Symbol font/0x61] mRNA expression, increase renal interleukin (IL)-10 mRNA expression, and improve the condition of ischemia/reperfusion-induced renal injury in rats. (See lines 19-22 of section 3 of page 840.) Moreover, Tsuji teaches the effects of orally administered TRPV1 agonists on leukocyte infiltration in LPS-induced acute lung injury and ovalbumin-induced allergic airway inflammation in rodents was investigated. In LPS-induced lung injury, capsaicin and SA13353 attenuated neutrophil infiltration and the increase in TNF-[Symbol font/0x61] and cytokine-induced neutrophil chemoattractant (CINC)-1 levels. In allergic airway inflammation, SA13353 tended to inhibit leukocyte infiltration and attenuated the increase in IL-4 and IL-12p40. These results suggest that at least somatosensory TRPV1 may play an anti-inflammatory role in lung inflammation. Inducing the cough reflex and modifying airway inflammation may be important functions of TRPV1 in body homeostasis. (See 24-32 of section 4 of page 841.) Tsuji further teaches SA13353 also reduces the levels of a number of cytokines, including TNF-[Symbol font/0x61], IL-1β, IL-12p40, IL-17, and interferon (IFN)-γ. (See lines 12-13 of page 842.)
Malaviya teaches increased levels of tumor necrosis factor (TNF-α) have been linked to a number of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sarcoidosis, and interstitial pulmonary fibrosis (IPF). TNFα plays multiple roles in disease pathology by inducing an accumulation of inflammatory cells, stimulating the generation of inflammatory mediators, and causing oxidative and nitrosative stress, airway hyperresponsiveness and tissue remodeling. TNF-targeting biologics, therefore, present a potentially highly efficacious treatment option. (See Abstract.) Moreover, Malaviya teaches in animal models of ALI or ARDS induced by endotoxin, mechanical ventilation, or extracorporeal circulation, TNFα has been implicated in disease pathogenesis. (See the last paragraph of page 6.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to use the formulation taught by Jones for treating COPD and ARDS, and
ARDS associated with mechanical ventilation, which is inflammation associated with mechanical ventilation by reducing TNF-α to give Applicant’s claimed method. One would have been motivated to do so, because not only Jones teach RTX which is a TrpV1 agonist and because Tsuji teaches RTX as a TrpV1 agonist can inhibit or reduce the increased levels of TNF-α and TRPV1 agonists on leukocyte infiltration in LPS-induced acute lung injury and ovalbumin-induced allergic airway inflammation, and also because increased levels of tumor necrosis factor (TNF-α) have been linked to a number of pulmonary inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). One would reasonably expect RTX to effectively treat COPD, ARDS, and ARDS associated with mechanical ventilation which is an inflammation disease associated with mechanical ventilation with success.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (US2019/0076396 A1) in view of Tsuji et al (. 2012 Aug 17;5(8):837–852) and Malaviya et al (Pharmacol Ther. 2017 Jun 19; 180:90–98) as applied to claims 1, 4-8, 11-20, and 22, in further view of Lee et al (Pain Physician. 2012 Jul-Aug;15(4):287-96).
The teachings of Jones, Tsuji, and Malaviya have been discussed supra.
Jones, Tsuji, and Malaviya collectively do not teach epidural administration.
Lee teaches RTX is highly selective for sensory nerve terminals expressing TRPV1 receptors without affecting proprioception and motor function. In many animal studies, RTX has been found useful for inflammatory pain, postoperative incisional pain, and bone cancer pain. It has been administered by variable routes: systemic by subcutaneous, intrathecal, epidural, intraganglionic, perineural, and directly to peripheral nerve endings. (See second paragraph of the left column of page 288.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the obvious method taught by Jones, Tsuji, and Malaviya by including epidural administration in order to treat COPD, ARDS, and ARDS associated with mechanical ventilation which is an inflammation disease associated with mechanical ventilation by reducing the underline pain associated with them. One would have been motivated to do so, because Lee teaches RTX has been administered by variable routes: systemic by subcutaneous, intrathecal, epidural, intraganglionic, perineural, and directly to peripheral nerve endings for treating inflammatory pain, postoperative incisional pain, and bone cancer pain. (See second paragraph of the left column of page 288.) One would reasonably expect to successfully treat COPD, ARDS, and ARDS associated with mechanical ventilation which is an inflammation disease associated with mechanical ventilation by reducing the underline pain associated with them with the obvious method taught Jones, Tsuji, and Malaviya.
Claims 21 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (US2019/0076396 A1) in view of Tsuji et al (. 2012 Aug 17;5(8):837–852) and Malaviya et al (Pharmacol Ther. 2017 Jun 19; 180:90–98) as applied to claims 1, 4-8, 11-20, and 22, in further view of Wu et al (J Microbiol Immunol Infect. 2020 Mar 11;53(3):368–370) and Wang et al (Vascul Pharmacol. 2013 Jan;58(1-2):71-7. Epub 2012 Jul 28).
The teachings of Jones, Tsuji, and Malaviya have been discussed supra.
Jones, Tsuji, and Malaviya collectively do not teach epidural administration.
Wu teaches COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients develop acute respiratory distress syndrome (ARDS), which leads to pulmonary edema and lung failure, and have liver, heart, and kidney damages. These symptoms are associated with a cytokine storm, manifesting elevated serum levels of IL-1β, IL-2, IL-7, IL-8, IL-9, IL-10, IL-17, G-CSF, GM-CSF, IFNϒ, TNFα, IP10, MCP1, MIP1A and MIP1B. (See the second paragraph of the left column bridging the right column of page 368.)
Wang teaches monocrotaline-induced pulmonary arterial hypertension is attenuated by TNF-α antagonists via the suppression of TNF-α expression and NF-κB pathway in rats. (See Title.) Moreover, Wang teaches inflammation is involved in various types of human pulmonary arterial hypertension (PAH), especially in PAH-associated connective tissue diseases. Although the pathogenesis of pulmonary hypertension has still remained largely unclear, TNF-α has been reported as a key pro-inflammatory cytokine in severe pulmonary hypertension and emphysema. (See Abstract.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the obvious method taught by Jones, Tsuji, and Malaviya by including PAH and ARDS associated with covid-19 which is a disease of inflammation associated with covid-19. One would have been motivated to do so, because not only Wu teaches many COVID-19 patients develop acute respiratory distress syndrome (ARDS), which leads to pulmonary edema and lung failure, and have liver, heart, and kidney damages and are manifested by elevated serum levels of TNF-α among others and also because TNF-α antagonists can attenuate pulmonary arterial hypertension via the suppression of TNF-α expression. One would reasonably expect to successfully treat PAH and ARDS associated with covid-19 which is a disease of inflammation associated with covid-19 with the obvious method taught Jones, Tsuji, and Malaviya.
Conclusion
Claims 1, 4-8, and 10-23 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEAN P CORNET/Primary Examiner, Art Unit 1628