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, 3-4, 6, 8, 10-11, 14, 16, 18, 20, 24-25, 27, 32, 41, 45-47 and 49 are pending and are under consideration in the instant office action.
Receipt and consideration of Applicants amended claim set and remarks/arguments filed on 04/08/2026 are acknowledged. . Claims 1, 16, 18, and 25 are amended. Claims under consideration in the instant office action are claims 1, 3-4, 6, 8, 10-11, 14, 16, 20, 22, 24-25, 27, 32, 41, 45-47 and 49.
Applicants' arguments, filed 8/4/2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Information Disclosure Statement
The two information disclosure statement (IDS) dated 8/4/2026 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.
Claim Rejections - 35 USC § 103
New grounds of rejection necessitated by the amendment dated 8/4/2026
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 of this title, 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 1, 3-4, 6, 8, 10-11, 14, 16, 18, 20, 24-25, 27, 32, 41, 45-47 and 49 rejected under 35 U.S.C. 103 as being unpatentable over Gerber et al. (US 2022/0008384, priority date 03/28/2019) and Nahama et al. (US 20210393515, priority date of 12/21/2018)
Instant claims are drawn to a method of preparing a subject for surgery, comprising perineurally administering RTX to a subject in need of surgery, wherein the RTX is administered at a dose of 5-100 µg, and wherein the RTX is administered to a plurality of sites.
Gerber et al. discloses method for postoperative pain control in a patient in need thereof, said method comprising a composition to a site intended for surgery in said patient at least one day before surgery is actually performed, wherein the composition comprises capsaicin or a capsacinoid such as resiniferatoxin (RTX) ([0007], [0030] reference Claim 1). Gerber discloses administration of 20-5000 ng of (which is 0.002 to 5 µg ) resiniferatoxin (reference Claim 7) and discloses wherein a dose of local anesthetic such as 0.1-5% bupivacaine is administered prior to, simultaneously with or posteriorly to the capsacinoid such as RTX administration (reference claim 8, reference claim 11, [0032-0033]). Gerber et al. discloses that particularly effective is the method to treat postoperative pain of orthopedic interventions and surgeries related to sports injuries, either from open, minimally invasive or arthroscopic surgery which may include joint replacement surgery, arthroplasty, debridement, cartilage repair, osteosynthesis, fracture treatment, treatment of ligament or tendon rupture or distortion (sprain), amputation, tumor or cancer surgery, in any joint, shoulder, elbow, hand, hip, knee, ankle or foot. [0009]. They disclose possible injection sites for RTX to include directly into the area of the surgical approach (skin incision, tissue preparation area) to the region of surgery, in the context of joint surgery around and or into (intraarticularly, into the synovial space) the joint space, to the sensory nerves connected to the area of surgery or as a regional or spinal anesthesia and they disclose that the site of infiltration may be defined by controlling of the needle position or the distribution of a contrast medium mixed with local anesthetics or RTX or being administered prior to this by means of fluoroscopy, radiographs, computer tomography or ultrasound. If the position of the injection needle or any suitable alternative administration tool (small catheter, tube) has been verified, it may be left in place to ensure the identical site of injection for a local anesthetic and the RTX solution. [0024-0026]. Gerber et al. discloses the volume of liquid to be injected into the intracapsular area may be from 0.1 to 150 ml. For a finger joint about max. 1 ml, for the shoulder joint max. 10 ml, for the knee joint max. about 30-50 ml, but preferably not over 20 ml [0023]. Gerber et al. further discloses compositions of the agents in a pharmaceutically acceptable vehicle, such as sodium chloride solution for injection, Ringer's solution for injection, isotonic dextrose, sterile water dextrose solution, Lactated Ringers injection solution, distilled water or mixtures thereof [0016] and discloses that RTX is preferably dissolved in a biocompatible solvent and is conveniently injected in an amount that corresponds to the available space in the joint to be treated so that it fills up easily to bulging and that the solvents may additionally contain permeation enhancer such as ethanol, phosphatidylcholines, propylene glycol dipelargonate (DPPG), or glycosylated glycerides [0020-0021], solubility enhancers such as benzyl alcohols, butylated hydroxytoluene’s, cremophores (EL, RH60), polyoxymethylene, sorbitanmonooleate or mannose to improve the activity of RTX. [0022]. They disclose buffering the solution with agents such as HEPES, phosphate, TRIS, Histidine, MOPS is required to establish the pH between 7.5 and 8.0 [0017].
Nahama et al. discloses administration of resiniferatoxin (RTX) perineurally in methods of treating maladaptive pain (claim 1). Nahama further discloses that during surgical or traumatic amputations, a substantial amount of trauma occurs in nerves and the surrounding tissue. This neural injury allows the sprouting of nerve endings, causing the terminals to become hyper-excitable, which is perpetuated and worsened by local inflammation. [0077]. Nahama et al. in addition disclose the inclusion criteria in their study wherein the subject has undergone surgery for treatment with RTX [0060-0061] Maladaptive pain is inclusive of chronic post-surgical pain which persists months after surgery beyond the healing time. Nahama et al. discloses where in the subject is a mammal such as a human or cat [0034], the subject is an amputee which would be a subject who has had surgery [0035], They disclose that RTX may be administered perineurally to one or more than one site [0038] (claim 5) at a dose of he RTX is administered at a dose of 0.1-100 μg perineurally or as a nerve block [0043]. Nahama et al. discloses formulations of RTX used comprising a pharmaceutically acceptable carrier comprising a) water; b) polysorbate 80; c) polyethylene glycol; d) a sugar or sugar alcohol; e) mannitol; f) dextrose; g) a pharmaceutically acceptable salt; and/or h) a pharmaceutically acceptable buffer (claim 14- 15) with a pH in the range of 6-7.6 (claim 23). They disclose that RTX is administered in an injection volume of 0.05-10 ml, optionally wherein the injection volume is in the range of 0.05-0.2 ml, 0.2-0.5 ml, 0.5-1 ml, 1-2 ml, 2-5 ml, or 5-10 ml (claim 32), They disclose wherein the concentration of RTX in the pharmaceutical formulation is in the range of 0.02-0.1 μg/ml, 0.1-1 μg/ml, 1-5 μg/ml, 5-10 μg/ml, 10-20 μg/ml, 20-50 μg/ml, 50-100 μg/ml, 100-150 μg/ml, 150-200 μg/ml, 200-250 μg/ml, or 250-300 μg/ml. (claim 29) and administering a dose of 0.1 μg to 100 μg of RTX, or a dose of RTX in the range of from 0.1-1 μg, 1-2 μg, 2-5 μg, 5-10 μg, 10-20 μg, 20-30 μg, 30-40 μg, 40-50 μg, 50-60 μg, 60-70 μg, 70-80 μg, 80-90 μg, or 90-100 μg.(claim 3).
Both Gerber et al. and Nahama et al. explicitly disclose the method of use of RTX at the concentration claimed which is between 5-100 µgm in preparing a subject for surgery by injecting it perineurally into nerves at the site. While they may not teach injecting it at plurality of sites, this would have been prima facial obvious to a person of ordinary skill in the art. Both these references provide clear motivation and guidance to a person of ordinary skill in the art to administer resiniferatoxin (RTX) perineurally in treatment of surgical pain. Application to plurality of sites which collectively correspond to sensory input from the surgical site would be obvious to a person of ordinary skill in the art, since RTX is already known in the art to be helpful in this method.
With regards to claims 3-4, 6, 8, 10 and 49 these are functional properties of the RTX and will occur when it is administered to the surgical site in a patient in need of surgery. Gerber et al. and Nahama et al. discloses the administration of the same drug to the same subject, at the same site for the same purpose as instantly claimed and as such these functional limitations of the treatment will inherently occur. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). 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. In addition, it is also noted that “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Therefore, the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains because it would have been prima facie obvious to the skilled artisan perineurally use RTX in a method to prepare the subject for surgery as it helps in reducing post-surgical pain. It would be routine optimization for a skilled artisan would be able to optimize the concentrations and the regimen to obtain the best result for the specific patient. 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). As such ordinarily skilled artisans will be imbued with at least a reasonable expectation of success in producing the instantly claimed method, especially in the absence of evidence to the contrary.
Response to applicant’s arguments filed on 8/4/2026:
In light of the new grounds of rejection above, the arguments submitted on 8/4/2026 which were for the previously submitted rejection is moot.
Conclusion
Claims 1, 3-4, 6, 8, 10-11, 14, 16, 18, 20, 22, 24-25, 27, 32, 41, 45-47 and 49 are rejected. No claims are allowed
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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 7.00 am to 4.00 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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