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 .
Reissue: Non-Final Office Action
Status of the Claims
On 4/21/2020 US Patent 10,624,945 issued to Ruff with claims 1-10. On 03/18/2022 applicant filed US Reissue Patent Application 17/698,065 (now RE50,630) for US Patent 10,624,945. On 05/20/2025 applicant filed the instant US Reissue Patent Application for US Patent 10,624,945, which is a CON of Reissue Application 17/698,065.
Claims 1-10 are canceled. Claims 11-28 were filed as new claims, and are currently pending in the instant reissue application. Claims 20-28 are withdrawn as discussed below. Claims 11-19 are the subject of this Office Action.
Maintenance Fees
Applicant is reminded of the requirement to pay all applicable maintenance fees on the original patent. See MPEP § 1415.01.
Ongoing Duty To Disclose
Applicant(s) is/are reminded of the continuing obligation under 37 CFR 1.178(b), to timely apprise the Office of any prior or concurrent proceeding in which Patent 10,624,945 is or was involved. These proceedings would include any trial at the Patent Trial and Appeal Board, interferences, reissues, reexaminations, supplemental examinations, and litigation.
Applicant is further reminded of the continuing obligation under 37 CFR 1.56, to timely apprise the Office of any information which is material to patentability of the claims under consideration in this reissue application.
These obligations rest with each individual associated with the filing and prosecution of this application for reissue. See also MPEP §§ 1404, 1442.01 and 1442.04.
Election/Restrictions
The inventions of claims 11-19 (Group I) are distinct from the invention of claims 20-28 (Group II), each from the other because of the following reasons:
Inventions I and II are directed to related methods. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed have a materially different design. Specifically, the method of claims 11-19 (Group I) requires administration of an opioid, whereas the method of claims 20-28 (Group II) does not. The method of claims 20-28 (Group II) only requires administration of a D peptide, which reduces risk of opioid addiction. A population can be at risk of opioid addiction without ever being administered an opioid. Thus, the methods of Group I and II are fundamentally distinct. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants.
Since applicant has received an action on the merits for the originally presented invention (i.e., in application 16/177,344), this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 20-28 (Group II) are withdrawn from consideration as being directed to a constructively non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
Applicant is advised that if the original patent claims are found allowable and no error (other than the failure to present the non-elected claims) is being corrected in the reissue application under examination, and a divisional application has been filed for the non-elected claims, further action in the application will be suspended, pending resolution of the divisional application. Otherwise, the claims to the original patented invention will continue to be examined and the non-elected claims (to any added invention(s)) will be held in abeyance in a withdrawn status. The non-elected claims will only be examined if filed in a divisional reissue application.
Information Disclosure Statement
References lined-through on the information disclosure statement(s) were not considered because they were not provided or were not provided with a proper publication date. 37 CFR 1.98(b) states that each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. Regarding website citations, it is noted that a date the website was accessed is not the same as a publication date.
Official Gazette Publication
The Official Gazette (O.G.) publication date for this reissue application was 09/02/2025.
Claim Rejections –
35 USC § 112(b) or (pre-AIA ) 35 USC § 112 (2nd Par.)
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.
Claims 11-19 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 11-19 are indefinite in the recitation "a therapeutically effective dose of the opioid is reduced as compared to the administration of the opioid alone to treat the condition," in claims 11 and 19. This limitation is indefinite because the claims use the phrase "a therapeutically effective dose" (emphasis added). Thus, the two "therapeutically effective doses" recited in the claim are not correlated with one another whatsoever. For example, the amount of opioid present in a DAPTA-containing composition intended for use in opioid-naïve children would be less than an opioid containing composition intended for use in an opioid tolerant adult, regardless of the presence or absence of a DAPTA peptide. Yet the DAPTA/opioid composition for children in this scenario could be compared to any other opioid containing composition (e.g., one intended for use in an opioid tolerant adult because it is "a pharmaceutical composition lacking the D peptide or DAPTA"), and still meet the claim.
The Federal Circuit has noted that "the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation." Halliburton Energy Servs., 514 F.3d at 1255 (Fed. Cir. 2008). Claims 12-18 depend from claim 11 and do not resolve the ambiguity. As such, claims 20-26 must be rejected under 35 U.S.C. 112(b).
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(a) 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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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 11-19 are rejected under 35 U.S.C. 103 as being unpatentable over PERT (US 2011/0245180; on IDS), RUFF (US 2014/0323393; on IDS), LI (Li, X., et al. Ann. Palliat. Med. (2012), 1(1); 53-57; on IDS), and KWIATKOWSKI (Kwiatkowski, K., et al. J. Neuroimmune Pharmacol. (2017), 12; 402-419).
Claims 11-19 recite a method of treating various types of pain (e.g., neuropathic pain) by administering a DAPTA peptide (having structure A-B-C-D-E as defined in the claim), an opioid, and a pharmaceutically acceptable carrier. As discussed below, Pert and Ruff teach compositions comprising DAPTA peptides without the inclusion of an opioid. However, Li establishes the longtime use of opioids in the treatment of neuropathic pain, particularly post-surgical pain. As in In re Kerkhoven (below), the inclusion/administration of opioid for this same purpose would have been prima facie obvious to one of skill in the art. Kwiatkowski establishes the motivation/expectation of using less opioid in a composition comprising a C-C chemokine receptor type 2 (CCR2) antagonist such as DAPTA peptides. The claimed invention would have been an obvious modification of these references.
Pert teaches a method of treating a post-surgical pain in a patient comprising administering a therapeutically effective dose of the chemokine receptor antagonist DAPTA, an octapeptide derived from HIV gp120, particularly all-D or TTNYT (SEQ ID NO:1), which is a D peptide of formula A-B-C-D-E, (abstract; [0003]-[0004], [0007], [0023], [0035], [0050]-[0080]). Pert teaches compositions comprising a pharmaceutically acceptable carrier (claims 1, 4, 7). Pert teaches a post-surgical model, particularly partial ligation of the sciatic nerve ([0003], [0017], [0023], [0035], [0038]-[0043], [0050], [0061], [0063], [0067]). Pert teaches chemokine signaling is important in neuropathic pain, with microglial cells expressing CCR2 playing a well-established key role. DAPTA is taught to exhibit potent antagonism for CCR2 (abstract; [0058]-[0060], [0068]). Pharmacological blockade by All-D TTNYT of CCR2 has therapeutic potential in injury associated-neuropathic pain ([0072], [0082]).
Ruff teaches managing pain in patients with brain injury and disease including from neuropathy, nerve injury, trauma and inflammation ([0002], [0008], [0010]-[0012], [0027]-[0045], [0047], [0049], [0094], [0099]; claims 2-3 and 11). Ruff teaches administering a composition comprising peptides of the recited formula A-H and/or C-H, 5-8 amino acids, which correspond to the recited peptides of formula A-E including All-D-TTNYT corresponding to claimed SEQ ID NO:1, All-D ASTTTNYT, and all-D DAPTA (Ruff SEQ ID NO:1-10, [0078]-[0079], claim 1).
Both Ruff and Pert recognize the benefit of the DAPTA peptide all-D TTNYT via the same mechanisms within post-surgical nerve injury pain, including particularly trauma, inflammation and binding at DAPTA pain receptors (i.e., CCR2). Specifically, Ruff teaches that DAPTA blocks CCR2 (i.e., DAPTA is a CCR2 antagonist) ([0083]-[0084], [0087]-[0088], [0099]; Table 1). Ruff taches treating pain in a nerve injury model ([0094]), which Pert teaches is a post-surgical nerve injury model as described above. Accordingly, one of skill in the art would have found it obvious to use DAPTA-containing compositions to treat post-surgical pain as exemplified within Ruff and Pert, particularly with all-D DAPTA peptide TTNYT (SEQ ID NO:1) for nociceptive effect as recognized in the art.
Ruff teaches the peptides may be used in combination with other pharmaceutically active compounds ([0055], [0076]), but Pert and Ruff do not specifically teach administration of opioids in combination with the peptides.
However, Li reviews advances in the use of opioids in treating neuropathic cancer pain (title; abstract), as well as the longstanding use of opioids treating nerve-injury pain. Li teaches that morphine and other opioids (e.g. oxycodone, fentanyl, methadone, tapentadol, tramadol, etc.) were known to effectively relieve neuropathic pain (including peripheral neuropathic pain) (pgs. 53-57).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a composition comprising all-D TTNYT (DAPTA) or all-D ASTTTNYT in combination with opioids and a pharmaceutically acceptable carrier, for use in the treatment of neuropathic pain.
“It is prima facie obvious to combine two compositions 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) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). See MPEP § 2144.06(I).
In this case, both the all-D DAPTA peptide (all-D TTNYT or ASTTTNYT) and various opioids were known in the art for the treatment of neuropathic pain (according to Pert, Ruff, and Li). Therefore, it would have been prima facie obvious to use the combination of all-D DAPTA and opioids as active agents along with a pharmaceutically acceptable carrier for the treatment of neuropathic pain (e.g., pain associated with post-surgical nerve injury).
Regarding the recitation "wherein the therapeutically effective dose of the pharmaceutical composition treats the condition in the patient and a therapeutically effective dose of the opioid is reduced as compared to the administration of the opioid alone to treat the condition," Kwiatkowski reports on the effect of a CCR2 antagonist (RS504393) on pain and its influence on opioid effectiveness (title; abstract). Like Pert and Ruff, Kwiatkowski teaches that C-C motif chemokine ligand 2 (CCL2) and its receptor C-C chemokine receptor type 2 (CCR2) play crucial roles in neuropathic pain development (p. 403, 1st col.). Administration of the CCR2 antagonist attenuated pain response in a model of neuropathic pain (p. 406, 2nd col.; Fig. 2; Discussion) and, critical to the examined claims, enhanced the analgesic properties of opioids (morphine and buprenorphine) under neuropathic conditions (abstract; p. 410, 2nd col.; Fig. 7; Discussion). Kwiatkowski teaches that CCR2 antagonism diminishes neuropathic pain and enhances opioid analgesic effects (abstract; Conclusion).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used a composition comprising an all-D DAPTA peptide in combination with an opioid to treat pain. In doing so, one would have been motivated to include less opioid than in an equivalent composition not comprising the all-D DAPTA peptide because Kwiatkowski teaches that CCR2 antagonists (like all-D DAPTA peptides) enhance opioid analgesic potency. Thus, when combining a CCR2 antagonist and an opioid, the artisan would have expected less opioid would be required to achieve the same analgesic effect. Including less opioid would have been recognized as beneficial since opioids are well-known to cause dependence, leading to addiction. Kwiatkowski directly provides motivation to use less opioid by teaching that treatment of neuropathic pain is a serious clinical problem, in part because of numerous undesired adverse effects of opioids that are commonly used in high doses (first sentence of the Introduction). Lower doses of opioids are clearly desirable.
Regarding claims 12-13 and 18, the all D TTNYT (SEQ ID NO:1) is a peptide in which the amino acids are all in the D stereoisomeric configuration (see Pert at pars. [0005], [0069]-[0070]). See also Ruff, teaching that all-D TTNYT or ASTTTNYT is SEQ ID NO:1 (an 8 amino acid peptide) in which the amino acids are in the D stereoisomeric configuration (abstract, [0049], [0073]-[0075]]).
Regarding claim 14, all-D TTNYT DAPTA are C-terminally amidated peptides (see Ruff at pars. [0049], [0074]).
Regarding claims 15-17, Pert is specific to liquid compositions, whereas Ruff also includes pill compositions. Ruff teaches the pharmaceutical composition is at a therapeutically effective dose to be administered orally in water (liquid saline) and in tablet form (i.e., a pill) at 0.05-500 mg (see Ruff abstract, [0056], [0058]-[0059], [0063], [0082]-[0083], [0085], [0092], [0096]). The pharmaceutical composition taught by Pert is liquid at 0.05-1 mg/kg in sterile water (liquid form), including for oral administration (abstract, [0014]-[0016], [0020]-[0021], [0040]-[0042], [0061]-[0062], [0072], [0074]).
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 obviousness-type 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); and 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
US Patent Application 17/869,925
Claims 11-19 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 20-26 of copending Application 17/869,925 optionally in view of KWIATKOWSKI (Kwiatkowski, K., et al. J. Neuroimmune Pharmacol. (2017), 12; 402-419). Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '925 claims anticipates or renders obvious that of the instant claims. The difference between the two claim sets is that the '925 claims recite a pharmaceutical composition comprising a D peptide/DAPTA, an opioid, and a pharmaceutically acceptable carrier. The '925 claims therefore read on the composition administered in the method of the instant claims. The '925 claims do not recite a method of treating the pain condition instantly recited. However, Pert, Ruff, and Li (discussed above and incorporated into this rejection by reference) establish that both the same D peptides and opioids were well-known in the art for the treatment of post-surgical pain, such as neuropathic pain. Thus the entire scope of the instant claims is an obvious variant of the '925 claims.
US Patent RE50,563
Claims 11-19 are non-provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 11-13 of US Patent RE50,563 in view of Pert, Ruff, and Li.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '563 claims anticipates or renders obvious that of the instant claims. The difference between the two claim sets is that the '563 claims recite a method of treating an opioid use disorder. The instant claims are drawn to a method of treating a variety of different pain conditions (disorders treated with opioids, i.e., opioid use disorders) wherein the dose of opioid is reduced as compared to administration of the opioid alone. Thus, the two claim sets encompass substantially similar subject matter, and both patient populations are considered to significantly overlap.
While most elements of the instant claims are anticipated by the '563 claims, the overall scope of the claims is not anticipated because the '563 claims do not recite the specific types of pain instantly recited. However, Pert, Ruff, and Li (discussed above and incorporated into this rejection by reference) establish that both the same D peptides and opioids were well-known in the art for the treatment of post-surgical pain, such as neuropathic pain. Thus the entire scope of the instant claims is an obvious variant of the '563 claims.
US Patent RE50,630
Claims 11-19 are non-provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-11 of US Patent RE50,630 in view of Pert, Ruff, and Li.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '630 claims anticipates or renders obvious that of the instant claims. The difference between the two claim sets is that the '630 claims recite a method of reducing an effective amount or duration of an opioid in a patient using said opioid to manage pain. The instant claims are drawn to a method of treating a variety of different pain conditions wherein the dose of opioid is reduced as compared to administration of the opioid alone. Thus, the two claim sets encompass substantially the same subject matter, with different wording. Both patient populations are undergoing treatment for pain, and recite a lower dose of opioid required due to the combination with the D peptide.
While most elements of the instant claims are anticipated by the '630 claims, the overall scope of the claims is not anticipated because the '630 claims do not recite the specific types of pain instantly recited. However, Pert, Ruff, and Li (discussed above and incorporated into this rejection by reference) establish that both the same D peptides and opioids were well-known in the art for the treatment of post-surgical pain, such as neuropathic pain. Thus the entire scope of the instant claims is an obvious variant of the '630 claims.
Conclusion
Claims 11-19 are rejected; claims 20-28 are withdrawn. No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kevin S Orwig whose telephone number is (571)270-5869. The examiner can normally be reached Mon.-Fri. 8AM-5PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle can be reached at (571) 272-6660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-9900.
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.
Information regarding the status of applications may be obtained from Patent Center. Patent Center is available to registered users regarding unpublished application information. To file and manage patent submissions, visit: https://patentcenter.uspto.gov and for more information visit https://www.uspto.gov/patents/apply/patent-center and https://www.uspto.gov/patents/docx. The fax number for the organization where this application is assigned is (571) 273-8300. For additional questions, contact the Electronic Business Center (EBC) at (866) 217-9197. If you would like assistance from a USPTO Customer Service Representative, call (800) 786-9199 or (571) 272-1000.
/Kevin S Orwig/
Patent Reexamination Specialist, Art Unit 3991
Conferees:
/Lora E Barnhart Driscoll/Patent Reexamination Specialist,
Art Unit 3991
/Patricia L Engle/SPRS, Art Unit 3991
Prosecution Insights