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
Claims 1-8 are pending and are under consideration in the instant office action.
Election/Restrictions
Applicant’s election of group 1 and the specie of piperlongumine without traverse of the following species in their response dated 6/22/2026 is acknowledged.
Applicants cancelled claim 9 and narrowed the claims to the elected specie.
Claims 1-8 are under examination and the requirement for restriction is made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/02/2024 and 05/13/2025 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
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Priority
This application claims the benefit of US patent application serial; no, 18/031,998 filed 04/14/2023, pct/us21/50425 filed 09/16/2021, U.S. provisional patent application Serial No. 63/078,571 filed September 15, 2020
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3 and 5-7 are rejected under 35 U.S.C. 102 (a) (1) and under 35 U.S.C 102(a)(2) as being anticipated by KR 20120122470 (from here on ‘470), referenced in the IDS dated 05/13/2025) as evidenced by Wargo et al. (Journal of pharmacy practice, volume 27, 2014, pages 573-577)
Instant claims are drawn to a stable pharmaceutical composition of compounds of method to prevent aminoglycoside toxicity comprising systemically co-administering to an animal or human, an aminoglycoside and an effective amount of Piperlongumine to prevent aminoglycoside toxicity and a method of preventing aminoglycoside toxicity, the method comprising administering a therapeutically effective amount of an active agent to downregulate TRPV1, or a pharmaceutically acceptable salt thereof and an aminoglycoside, wherein the active agent is Piperlongumine; or a pharmaceutically acceptable salt thereof.
Regarding claim I and 5, ‘470 teaches a method to prevent or treat hearing loss (abstract, The present invention relates to a pharmaceutical composition and a food composition for preventing and treating inner ear damage, containing a subfraction of a Piper longum L. extract asan active ingredient; see also pg 3, para 7, The inner ear damage disease as defined in the present invention is characterized by being caused by the death of auditory hair cells and includes tinnitus, hearing loss(hearing loss), dizziness, dizziness and the like) comprising: administering to an animal or human in need thereof an effective amount of a pharmaceutical composition containing a therapeutically active agent (pg 3, para 11, An effective amount of a pharmaceutical composition according to the present invention means an amount ofan active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, an animal or a humanbeing considered by a researcher, veterinarian, physician or other clinician. inducing a reduction of the symptoms of the disease ordisorder), wherein the therapeutically active agent is selected from the group consisting of: Piperlongumine or a derivative ofPiperlongumine. (pg 6, para 1, The main chemical components of the volatile oils are volatile oils, resins and alkaloids, namely piperine, piperlongumine and piperionguminine).
Regarding claim 2 and 6, ‘470 further teaches the method comprising protecting the inner ear cells from death caused by an antibiotic (pg 2, para 2, A typical drug causing this toxicity is aminoglycoside antibiotics such as gentamicin (GM), and when it is taken in long term / high dose, sensorineural hearing loss and dizziness are induced).
Regarding claim 3 and 7, ‘470 further teaches wherein the antibiotic is an aminoglycoside (pg 2, para 2, A typical drug causing this toxicity is aminoglycoside antibiotics such as gentamicin (GM), and when it is taken in long term / high dose, sensorineural hearing loss and dizziness are induced). Aminoglycosides are well known in the art as drugs which causes ototoxicity and nephrotoxicity. Wargo et al. is used here as an evidentiary document to show that Aminoglycosides are notorious for causing nephrotoxicity and renal problems (see abstract). And the aminoglycoside recited by ‘470 will inherently cause renal toxicity absence of evidence to the contrary. In accordance with MPEP §2131.01, it is proper to rely upon a secondary reference for a rejection under 35 U.S.C. 102, provided that the additional reference is relied upon to demonstrate that a characteristic or property not disclosed by the primary reference is, in fact, inherent.
Regarding claim 5, downregulation of TRPV1 is a functional property of Piperlongumine and would inherently occur in the Piperlongumine taught by ‘470. It is also noted that, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430,433 (CCPA 1977). See also MPEP § 2112.01 with regard to inherency and product-by-process claims.
Therefore the method and composition disclosed by ‘470 . fully anticipates instant claims 1-3 and 5-7.
Claims 1-3 and 5-7 are rejected under 35 U.S.C. 102 (a) (1) and under 35 U.S.C 102(a)(2) as being anticipated by Du et al. (Pharmazie 67, 2012, pages 559-563))
Instant claims are as recited above,
Du et al. discloses that Piper Lonngum (PL) showed a significant and concentration dependent protective effect against gentamycin (GM) induced hair cell loss and hair cells retained their stereocilia well in the cochlea (abstract) and they suggest that it might be of therapeutic benefit for treatment of Gentamycin induced ototoxicity (abstract). They disclose that gentamycin is a widely used aminoglycoside limited by their ototoxicity and nephrotoxicity (page 559, col.1, 1st para). They disclose that GM can induce hearing loss due to destruction of inner ear hair cells……Many studies have reported that GM-induced ototoxicity is commonly regarded as being mediated by reactive oxygen species and reactive nitrogen species. Overproduction of ROS triggers the signaling pathway of cellular apoptosis , resulting in inner ear damage (page 559, col.2). They disclose that the chemical constituents of PL extract include piperine, pipalartene, piperlongumine (page 559, col.2)
Accordingly Du et al. fully anticipates the instant claims,
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 4 and 8 are rejected under 35 U.S.C. 103(a) as being unpatentable over KR 20120122470 (from here on ‘470, referenced in IDS dated 5/13/2025) as they apply to claims 1-3 and 5-7 in the 102 rejection
Instant claims are drawn to a wherein the concentration of the piperlongumine ranges from 0.1pM to 25uM.
‘470 discloses as recited above and is applied here in the same manner. In addition ‘470 discloses that an effective amount of R pharmaceutical composition according to the present invention means an amount of an active ingredient OF pharmaceutical composition that induces a biological or medical response in tissue system, animal or human being considered by researcher, veterinarian, physician or other clinician for reduction of the symptoms of the disease or disorder. It will be apparent to those skilled in the art that the therapeutically effective dose and the number of administrations of the active Ingredient of the present Invention will very depending on the desired effect. Thus, the optimal dosage to be administered can be readily determined by those skilled in the art and will vary with the nature of the disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, and the age, The age, body weight, sex, diet, time of administration, route of administration and fraction of the composition, duration of treatment, concurrent medication, and the like. In the treatment method of the their invention, ‘470 discloses, in the case of an adult, it is preferable to administer the composition of the present invention at a dose of 1 / kg to 250 / kg once to several times a day. As such ‘470 provides a starting range for a person of ordinary skill in the art to optimized the concentration, upon which they can arrive at the instantly claimed composition. It is noted 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).
Conclusion
Claims 1-8 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/ Primary Examiner, Art Unit 1691
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