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 .
Election/Restrictions
Applicant’s election without traversal of the species of a single and specific amino acid sequence comprised in the peptide as RAP-103 (All-D peptide Thr-Thr-Asn-Tyr-Thr) (TTNYT) (SEQ ID NO:2), and Applicant’s election without traversal of second therapy as an opioid, in the reply filed on August 5, 2026.
The species elected without traverse, therefore, claims 29, 31, and 33-48 which read upon the elected species has been considered.
Claims 29, 31-48 are hereby examined on the merits. Election was made without traverse in the reply filed on August 5, 2026.
Claim 30 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 13, 2026.
Priority
This application is a 371 of PCT/US2022/032835, filed June 9, 2022. This application claims the benefit of U.S. Provisional Application No. 63/208,517, filed June 9, 2021.
Status of Claims
Claims 29-48 are pending. Claims 1-28 were previously cancelled.
The amendment filed on August 5, 2026, amended claims 31 and 32. Claim 30 is withdrawn for further consideration.
Claims 29 and 31-48 are currently examined on the merits herein.
Information Disclosure Statement
Information disclosure statements (IDS) submitted by the applicant on 11/15/2023, 06/18/2024, 07/25/2024, 10/23/2024, 02/19/2025, 04/21/2025, 08/01/2025, and 11/07/2025 are in compliance with the provisions of 37 CFR 1.97. It has been considered by the examiner.
Specification
The use of the terms Invitrogen which are trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , ® or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Interpretation
Legal standard: Broadest Reasonable Interpretation (BRI):
BRI of claim 29 and dependent claims is a method of administering a peptide to treat Persistent Postsurgical Pain (PPSP), the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition to treat PPSP, wherein the pharmaceutical composition comprises: a peptide or a salt thereof, wherein the peptide comprises at least five contiguous amino acids, wherein the PPSP is a clinical discomfort that lasts more than 3 months post-surgery. The claim is given this construction in view of the election of species of peptide sequence of 5 amino acids TTNYT (SEQ ID NO:2).
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 37-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the instantly claimed invention is enabled for treating Persistent Postsurgical Pain (PPSP), however, does not reasonably provide enablement for treating subject has any pain catastrophizing or such that the administering increases dopamine levels in the subject in need thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The nature of the invention and the breadth of the claims
The claims are drawn to a method of treating PSPP comprising administering to a subject with an amount effective of a compound (peptide plus second therapy); wherein the PPSP comprises treating pain.
Embodiments of the instant specification the subject has pain catastrophizing. In some embodiments, the method can further comprise increasing dopamine levels in the subject in need thereof (see [0004]).
However, treating all pain as claimed reads on administering effective amount of the compound to any individual with PPSP. The specification does not teach a method of treating all types of catastrophizing pain experienced by a patient in need, using the therapeutic composition as claimed, nor does it show increase in dopamine levels in the subject. Accordingly, claims 37 and 38 are unduly broad with respect to a method of treating all PPSP.
The State of the Prior Art and The Level of Predictability in the Art
The state of the art at the time of filing did not recognize that the claimed compound could prevent a range of PPSD or related conditions. For instance, while Applicants are enabled for treating a subset of chronic pain (see instant [0016]) and neuronal repair (see instant [0020]), and prior art below (catastrophizing pain in limb amputees, see Cintron), the art does not recognize that all PPSP can be treated, let alone with designed inhibitory compounds such as the instant composition. Although the instant specification states the method can be used to treat PPSP, there is no prior art that teaches the instant composition of claim 1 can treat any type of catastrophizing pain or increase dopamine level. Prior art has investigated therapeutics for treating PPSP related pain and side effects, that suggest that therapeutic treatment for any PPSP might be possible someday but is presently not an option.
The Level of Skill in the Art
Practitioners in this art (clinicians, scientists) would presumably be highly skilled in the art for prevention or treatment of disease in a subject.
The Amount of Direction Provided by the Inventor
At the time of filing, no direction or guidance was presented in either the prior art or the instant specification that would enable one to administer the instant compound to treat any PPSP as claimed. The instant specification does not provide adequate guidance with regard to the actual treatment or the effective amount of the compound that is required to prevent any PPSP. Applicants’ limited disclosure is noted but is not sufficient to justify claiming treatment of any kind of chronic/neuronal pain in a subject broadly. Absent a reasonable a priori expectation of success for using the composition as a method of treatment, one skilled in the art would have to extensively test the inhibitor compound on a representative number of subjects, determine dosing using different concentrations of the compound and ascertain a prevention standard.
The Presence or Absence of Working Examples
The instant specification provides no examples wherein compound is administered to any kind of catastrophizing pain related to PPSP.
The Quantity of Experimentation Necessary
As there are no working examples in either the instant specification nor the prior art, reasonable guidance with respect to treating catastrophizing pain related to PPSP through administration of the compound was limited. Consequently, one skilled in the art would be burdened with undue experimentation to determine the precise parameters and conditions necessary to effectively treat catastrophizing pain related to PPSP and measure of increase in dopamine levels.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide sufficient information to practice the claimed invention for the treatment of any kind of catastrophizing pain related to PPSP and measure of increase in dopamine levels.
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.
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 29, 31-37, and 39-48 are rejected under 35 U.S.C. 103 as being unpatentable over US20110245180 (published October 6, 2011; cited in IDS filed November 15, 2023) in view of Cintron (“Persistent Postsurgical Pain”, Pract Pain Manag. 2012;12(4); published 2012; last updated June 19, 2017), and further in view of US2019125823 (published May 2, 2019; cited in IDS filed November 15, 2023).
US’180 discloses a method of treatment of disease by a chemokine receptor antagonist pharmaceutical composition comprising all D TTNYT peptide (claims 1 and 4); all D TTNYT relieves pain hypersensitivity probably through either or both chemokine receptors CCR2 and CCR5, since by using genetically deficient animals (see Abstract). US’180 demonstrated that in addition to CCR2, CCR5 is also required for the development of neuropathic pain, and all D TTNYT is able to reduce spinal microglial activation, …. inhibit inflammatory responses evoked by peripheral nerve injury that cause chronic pain (see Abstract). US’180 teaches that targeting CCR2/CCR5 should provide greater efficacy than targeting CCR2 or CCR5 alone and dual CCR2/CCR5 antagonist all D TTNYT has the potential for broad clinical use in neuropathic pain treatment (see Abstract).
US’180 is silent about treating clinical discomfort that lasts more than 3 months post-surgery nor discloses use of second therapy for the treatment of persistent postsurgical pain.
Cintron elaborates regarding persistent postsurgical pain and teaches strategies for the identification of patients at risk for persistent postsurgical pain and, as well as possible treatment strategies (see Abstract paragraph 4). Cintron teaches Postsurgical pain is defined as pain lasting more than 3 to 6 months after surgery; the pain differs in quality and location from pain experienced prior to surgery, and is usually associated with iatrogenic neuropathic pain caused by surgical injury to a major peripheral nerve (see Abstract paragraph 2). Cintron further teaches surgery, by nature, involves the cutting of tissues and nerves, which induces the injury response (inflammation, hyperalgesia) and alterations of peripheral and central nervous system (CNS) pain processing (central sensitization), which can lead to chronic pain (see Mechanisms and Science, paragraph 2, Figure 1); surgery increases synaptic activity in dorsal horn neurons. Humoral signals released from inflamed tissue act on the CNS and intracellular kinases. Within hours, altered gene transcription in the dorsal root ganglion (DRG) of sensory neurons and the spinal cord augment release of excitatory transmitters and reduce inhibitory transmitters. This results in neuronal excitability lasting days (see Mechanisms and Science, paragraph 3). Cintron also mentions that interventions at one or more sites along the pain pathway are recommended to be performed prior to incision; include infiltration of the incision site with local anesthetics (ie, bupivacaine, lidocaine), performance of regional nerve blocks and epidural or subarachnoid blocks, as well as initiating medications (non-steroidal anti-inflammatory drugs [NSAIDS], NMDA blockers, and opioids) (see How to Prevent or Minimize Postsurgical Pain, paragraph 2).
US’823 discloses a method of treatment of pain in a patient comprising the steps of:
preparing a composition comprising a D peptide, administering said composition to the patient in a therapeutically effective dose, wherein said composition acts to treat painful conditions, alone or in combination with opioids in the patient to reduce or eliminate the amount or duration of opioid use to manage their pain (see claim 1).
Therefore, it would have been obvious to combine the teachings of US’180, US’823, and Cintron before the effective filing date of the claimed invention by administering the peptide composition along with second therapy of opioid for treating persistent postsurgical pain. One of ordinary skill in the art can administer the composition for inhibiting neuroinflammation (see US’180, Abstract), for improving the management of acute intra- and postoperative pain (see Cintron, Conclusion) and supporting neuronal repair with a reasonable expectation of success in the treatment of persistent postsurgical pain. Thus, one skilled in the art would be motivated to use potential peptide composition for broad clinical use in neuropathic pain treatment for the treatment of persistent postsurgical pain in the affected area with limited experimentation requiring verifying the effect of treatment.
It is prima facie obvious to combine two compositions (i.e., peptide all D TTNYT and second therapeutic component opioid) each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See MPEP 2144.06(I).
Regarding claims 29, and 31: US’180 discloses a pharmaceutical composition comprising all D TTNYT peptide and a pharmaceutically acceptable carrier (see claim 7); all D TTNYT has the potential for broad clinical use in neuropathic pain treatment (see Abstract); and the method of treatment of inflammatory disease wherein said inflammatory disease is painful neuropathy (see claim 3).
Regarding claims 37, 39, and 43-45: Cintron teaches pain is the result of the interaction between biological and psychological variables. Preoperative anxiety and pain are correlated with the development of more postoperative pain. For example, catastrophizing in limb amputees contributes to phantom limb pain (see Psychosocial Factors).
US’823 teaches a method of treatment of pain in a person with a D peptide chemokine receptor antagonist, and a pharmaceutically acceptable carrier is disclosed; because chemokines desensitize opiate receptors and enhance the perception of pain said D-peptide CRA, given with a suboptimal dose of an opioid….will restore opioid analgesic efficacy by blocking the cognate chemokine ligand from binding to its receptor and desensitizing the opioid receptor (see Abstract). US’823 discloses a method of treatment of pain in a patient comprising the steps of: preparing a composition comprising a D peptide and a pharmaceutically acceptable carrier, said D peptide further comprises five contiguous amino acids having the general structure….. administering said composition to the patient in a therapeutically effective dose, wherein said composition acts to treat painful conditions, alone or in combination with opioids (see claim 1). US’823 further discloses a method of pain treatment wherein said chemokine receptor antagonist may be combined, as in a pill or liquid with an opioid to provide pain relief at lower opioid dose (see claim 10).
Regarding claim 32-36, and 42: : US’823 discloses a method of treatment of pain in a patient comprising a D peptide and a pharmaceutically acceptable carrier; wherein said D peptide is TTNYT; wherein E (i.e., E is Thr, Ser, Arg, Gly) may be esterified, glycosylated, or amidated to enhance tissue distribution (see claims 1, 2, and 4) [Note: For the instantly claimed invention, peptide TTNYT has E as Thr (T)]. US’180 teaches a method of treatment comprising, an all D TTNYT peptide, a pharmaceutically effective carrier, and administering said pharmaceutical composition in an effective dose to a patient (see claim 1); a method of treatment of disease by a chemokine receptor antagonist pharmaceutical composition comprising administering said pharmaceutical composition in an effective dose to a patient suffering (see claim 4); wherein said chemokine receptor antagonist interacts with multiple chemokine receptors (see claim 6); and a pharmaceutical composition comprising all D TTNYT peptide and a pharmaceutically acceptable carrier (see claim 7). Additionally, US’180 elucidates dose response curves of morphine (opioid) alone compared to morphine plus RAP-103 (see [0010] and FIG. 5). US’180 teaches oral administration of all D TTNYT; US’823 teaches the peptides may be dosed as an oral pill, suspension, liquid, or by IV and subcutaneous injections to achieve pain control (see [0011]).
Regarding claims 40, 41, and 48: US’180 exemplifies all D:TTNYT Treatment Paradigms, prevention: d0-d7 post-injury, 0.05, 0.1, 1 mg/kg daily post operation (p. o.) (see [0028], reversal: d8-d12 post-injury, 0.1, 0.2, 1 mg/kg daily p. o. (see [0029]); all D TTNYT (0.05, 0.1 or 1 mg/kg by weight p. o.) administered immediately after surgery and continued once daily for 7 days following nerve injury (see [0040]). US’180 further discloses oral administration of All D TTNYT (0.05-1 mg/kg) for 7 days…, administered from day 8 to day 12, All D TTNYT (0.2-1 mg/kg) (see Abstract); oral administration of All D TTNYT (0.1, 0.2, and 1 mg/kg) (see [0021]).
Additionally, US’823 discloses a method of treatment of pain by a chemokine receptor antagonist pharmaceutical composition in which said composition is used at a concentration between 0.5 to 100 mgs as an oral pill (see claim 5); in which said composition is used at a concentration between 0.1 to 500 mgs as an oral pill (see claim 6).
It is prima facie obvious to combine the teachings of US’180 and US’823 to estimate the dose of the pharmaceutical composition to be administered. The concentration of the US’180 and US’823 are disclosed as mg/kg body weight and this range overlaps with the instant invention dose concentration as the specification states that the dosage the amount of the polypeptide, or the derivative thereof, or the salt of any of these can be dosed in an amount ranging from about 0.0001 mg/kg of body weight of the subject to about 1000 g/kg of body weight of the subject; the dosage can be, for example, based on mg of polypeptide, derivative thereof, or salt thereof, per kg of subject body weight, can be about: 0.0001, 0.001, 0.01, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 g/kg of subject body weight (see [0097]).
Regarding claims 46 and 47: US’180 studied monocytes treated with the indicated doses of All D TTNYT for 30 minutes prior to chemotaxis against human MCP-1 or MIP-1β (see [0019], FIG.9); for tissue preparation unilateral partial ligation of the sciatic nerve causing partial injury of somatosensory fibers with a rapid and long-lasting hypersensitivity (allodynia and hyperalgesia) is a rat model of human neuropathy was used (see [0023]); purified human monocytes (>95%) prepared from healthy adult human donors (see [0037]); and tested the ability of all D TTNYT to antagonize the function of chemokine receptors by blocking the chemotactic migration of human monocytes in the presence of specific ligand (see [0060]). US’823 disclosed that the effective human doses suggested by these animal studies would be 0.01 to 2 mg/Kg/day (see [0011]).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 29, 31-36, and 39-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 10 of U.S. Patent No. 10, 624,945 (issued April 21, 2020). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Regarding claims 29, 31-36, 40-42, and 48: US’945 claims a method of reducing the effective amount or duration of opioid in a patient using said opioids to manage pain comprising the steps of: preparing a chemokine receptor antagonist pharmaceutical composition comprising an all-D peptide and a pharmaceutically acceptable carrier, said peptide comprises five contiguous amino acids….all amino acids being the D stereoisomeric configuration and, administering said composition to the patient in a therapeutically effective dose, wherein said composition acts to manage pain (see claim 1); wherein said D peptide is TTNYT (see claims 2 and 3); wherein E is esterified, glycosylated, or amidated to enhance tissue distribution (see claim 4); wherein said composition is used as an oral pill having between 0.5 to 100 mgs of the peptide (see claim 5); wherein said composition is used as an oral pill having between 0.1 to 500 mgs of the peptide (see claim 6); wherein said chemokine receptor antagonist reduces the effective amount of opioid use by the patient (see claim 7); and a method of pain treatment wherein said chemokine receptor antagonist is administered as a pill or liquid (see claim 10).
Regarding claims 43-45: US’945 teaches A method of treatment of pain in a person with a D peptide chemokine receptor antagonist (CRA), and a pharmaceutically acceptable carrier is disclosed. Because chemokines desensitize opiate receptors and enhance the perception of pain said D-peptide CRA, given with a suboptimal dose of an opioid (see Abstract). US’945 specifies that the peptides may be dosed as an oral pill, suspension, liquid, or by IV and subcutaneous injections to achieve pain control with decreased concomitant opioid use (see col 2, line 36-39).
Regarding claims 39, 46, and 47: US945 specifies This strategy of combining a suboptimal dose of morphine with a CRA enhances the potency of morphine, permitting use of lower doses of morphine to obtain equivalent and near maximal analgesia. Lower morphine (opioid) doses have less risk of adverse effects (see Abstract). US’945 also shows RAP103 potentiates morphine analgesia in an animal model of post-surgical pain (see FIG. 4). US’945 further specifies The effective human doses suggested by these animal studies would be 0.01 to 2 mg/Kg/day (see col 2, line 35-36).
Regarding the instant claim where method of administering a peptide to treat Persistent Postsurgical Pain (PPSP) in a subject, US’945 specifies in view of the results showing that chemokines reduce opioid efficacy, these results suggest that administration of a chemokine receptor antagonist, like R103 (all-D-TTNYT), or related all-D-pentapeptides of the list below, will reduce pain by any cause, but especially inflammatory pain, to include back pain, post-surgical pain, neuropathic pain (see col 2, line 27-32).
It would have been prima facie obvious to one of ordinary skill in the art to modify the claims of US’945 by administering the peptide composition along with second therapy of opioid for treating persistent postsurgical pain. One of ordinary skill in the art can estimate the dose of the pharmaceutical composition to be administered, as the concentration of this range overlaps with the instant invention dose concentration, and administer the composition for improving the management of acute intra- and postoperative pain supporting neuronal repair with a reasonable expectation of success in the treatment of persistent postsurgical pain. Thus, one skilled in the art would be motivated to use the same D peptide composition as chemokine receptor antagonist for broad clinical use in neuropathic pain treatment and for the treatment of persistent postsurgical pain in the affected area.
Claims 29, 31-36, and 39-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,130,674 (issued November 20, 2018; cited in IDS filed November 15, 2023), in view of US20110245180 (published October 6, 2011; cited in IDS filed November 15, 2023), and further in view of US2019125823 (published May 2, 2019; cited in IDS filed November 15, 2023). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
US’674 discloses the short peptide All D TTNYT (SEQ ID NO:1) exhibits potent antagonism for both CCR2 (IC50 4.2 pM) and CCR5 (IC50 0.18 pM) in monocyte chemotaxis; oral administration of All D TTNYT (SEQ ID NO:1) (0.05-1 mg/kg) for 7 days fully prevents mechanical allodynia and inhibits the development of thermal hyperalgesia following partial ligation of the sciatic nerve in rats; administered from day 8 to day 12, All D TTNYT (SEQ ID NO:1) (0.2-1 mg/kg) reverses already established hypersensitivity; All D TTNYT (SEQ ID NO:1) relieves pain hypersensitivity probably through either or both CCR2 and CCR5; moreover, All D TTNYT (SEQ ID NO:1) is able to reduce spinal microglial activation, monocyte infiltration, and to inhibit inflammatory responses evoked by peripheral nerve injury that cause chronic pain (see Abstract).
US’674 claims a method of treatment of pain from inflammation comprising preparing an All D TTNYT (SEQ ID NO:1) pharmaceutical composition comprising, an All D TTNYT (SEQ ID NO:1) peptide, a pharmaceutically effective carrier, and administering said pharmaceutical composition in an effective dose to a patient suffering pain from inflammation (see claim 1); wherein said pain from inflammation is caused by painful neuropathy (see claim 2); wherein said pain from inflammation is caused by diabetic painful neuropathy (see claim 3); and wherein said pain from inflammation is caused by a condition selected from the group consisting of: fibromyalgia, endometriosis, abdominal pain, arthritis, cancer, muscle pain and joint pain (see claim 4). US’674 specifies oral administration of All D TTNYT (SEQ ID NO:1) (0.05, 0.1, or 1 mg/kg, p.o., d0-d7) (FIG. 10A).
The claims of US’674 differ from the instant claims in that they do not specify about administering the peptide to treat Persistent Postsurgical Pain (PPSP) in a subject nor does it mention about use of opioid as second therapy.
The teachings of US’180 and US’823 are discussed above.
It would have been obvious to combine the teachings of US’674, US’180, and US’823, before the effective filing date of the claimed invention by administering the peptide composition along with second therapy of opioid for treating persistent postsurgical pain. One of ordinary skill in the art can administer the composition for inhibiting neuroinflammation, for improving the management of acute intra- and postoperative pain, and for supporting neuronal repair with a reasonable expectation of success in the treatment of persistent postsurgical pain. Thus, one skilled in the art would be motivated to use the peptide composition for broad clinical use in neuropathic pain treatment for the treatment of persistent postsurgical pain in the affected area with limited experimentation requiring verifying the effect of treatment.
Claims 29, 31-36, and 39-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 5,534,495 (issued July 9, 1996; cited in IDS filed November 15, 2023), in view of US20110245180 (published October 6, 2011; cited in IDS filed November 15, 2023), and further in view of US2019125823 (published May 2, 2019; cited in IDS filed November 15, 2023). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
US’495 teaches a method for treating non-HIV related neuropathic pain syndrome in mammals which comprises administering an effective amount of a peptide of the formula (I):
R.sup.a -Ser-Thr-Thr-Thr-Asn-Tyr-R.sup.b, wherein Ra represents an amino terminal residue which is Ala-, D-Ala, or Cys-Ala; and Rb represents a carboxy terminal Thr- or Thr-amide an ester or amide derivative thereof (see claims 1, 5, and 6) [Note: The peptide sequence of US’495 is 100% homologous to the instant TTNYT (SEQ ID NO: 2)].
US’495 further claims the method which comprises administering an effective amount of a peptide of the formula (I-III) or a physiologically acceptable salt thereof (see claims 2-4); wherein said peptide is administered intranasally or sublingually (see claims 7-12); wherein said peptide is administered intranasally, daily, in three substantially equally spaced applications, the combined daily applications containing a total of from about 0.02 to 50 mg of said peptide (see claim 13); wherein the combined application contains about 1.2 mg of said peptide (see claim 14); wherein the combined application contains about 6 mg of said peptide (see claim 15); wherein the combined application contains about 30 mg of said peptide (see claim 16); wherein the combined application contains about 0.2 mg of said peptide (see claim 17); and A method for treating non-HIV related neuropathic pain syndrome in mammals which comprises administering an effective amount of D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-amide and physiologically acceptable salts thereof to the mammal (see claim 18).
US’495 specifies that the invention provides a pharmaceutical composition comprising a peptide compound of the invention in association with pharmaceutically acceptable carrier or excipient, adapted for use in human or veterinary medicine; such compositions may be presented for use in a conventional manner in admixture with one or more physiologically acceptable carriers or excipients; the compositions may optionally further contain one or more other therapeutic agents; the peptides according to the invention may be formulated for oral, sub-lingual, intranasal, buccal, parenteral, topical or rectal administration (see col 4, line 29-40).
The claims of US’495 differ from the instant claims in that they do not specify about administering the peptide to treat Persistent Postsurgical Pain (PPSP) in a subject nor does it mention about use of opioid as second therapy.
The teachings of US’180 and US’823 are discussed above.
It would have been obvious to combine the teachings of US’495, US’180, and US’823, before the effective filing date of the claimed invention by administering the peptide composition along with second therapy of opioid for treating persistent postsurgical pain. One of ordinary skill in the art can administer the composition for inhibiting neuroinflammation, for improving the management of acute intra- and postoperative pain, and for supporting neuronal repair with a reasonable expectation of success in the treatment of persistent postsurgical pain. Thus, one skilled in the art would be motivated to use the peptide composition for broad clinical use for treating neuropathic pain including treatment of persistent postsurgical pain.
Conclusion
No claim is allowed.
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/KOYELI BANERJEE/ Examiner, Art Unit 1658
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
