DETAILED ACTION
This office action is in response to applicant’s filing dated January 22, 2026.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 22, 2026 has been entered.
Status of Claims
Claims 1-20 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed January 22, 2026. Acknowledgement is made of Applicant's amendment of claims 1 and 2.
Claims 1-20 are presently under examination.
Priority
The present application claims benefit of US Provisional Application No. 63/636,022 filed on April 18, 2024.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, US Provisional Application No. 63/636,022, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In a review of the provisional application, disclosure of the therapeutic amount of SRP-001 is less than or equivalent to a dose of acetaminophen (ApAP) effective to treat the pain intensity of the subject (instant claim 1); SRP-001 induces analgesia by generating a greater amount of N- arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject compared to an equivalent amount of ApAP (instant claim 1); the effective amounts of instant claim 3; interval of 12 hours (instant claim 5); administered parentally, transdermally, topically, or nasally (instant claim 6); composition further comprising one or more pharmaceutically acceptable excipients, carriers, or a combination thereof (instant claim 7), the amounts and wetting agent of instant claims 8-14; the composition in the form of a pill, cream, spray or lotion (instant claim 15); particle size of instant claim 16; and the reduction in risk of hepatotoxicity of instant claim 18 was not identified. Thus, the provisional application does not provide adequate support in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for claims 1-20. Thus, the effective filing date of claims 1-20 is April 17, 2025.
Withdrawn Objections and/or Rejections
Claim Rejections - 35 USC § 112
Applicant’s arguments with respect to the rejection of claims 1-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement have been fully considered and are persuasive. Thus, the rejection has been withdrawn.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
Claim Rejections - 35 USC § 102
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 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.
Claims 1-7, 15, and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bazan et al (WO 2019/040122 A1, cited in the IDS filed April 30, 2025, hereinafter referred to as Bazan ‘122).
Regarding claim 1, Bazan ‘122 teaches a method of ameliorating pain in a subject comprising administering to said subject afflicted with pain a therapeutically effective amount of the analgesic compound (claim 33) having the chemical structure (claim 9):
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This compound reads on SRP-001 as evidenced by the instant specification (see paragraph [0059]).
Although the reference does not specifically identify that SRP-001 induces analgesia by generating a greater amount of N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject compared to an equivalent amount of ApAP, the method steps are the same. A chemical composition and its properties are inseparable. Thus, in practicing the methods of Bazan ‘122, (i.e. administering SRP-001 to ameliorate pain), SRP-001 would possess the characteristic of inducing analgesia by generating N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject. 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 includes functions and/or properties 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 to be shown in the prior art does not possess the characteristic relied on" (205 USPQ 594, second column, first full paragraph). There is no requirement that a person of ordinary skill in the art would have recognized the newly cited function and/or property at the time of invention, so long as the function and/or property can be demonstrated to be reasonably expected to be present. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention").
Regarding the limitation assessing the intensity of the pain in the subject, Bazan ‘122 teaches two different assays were utilized to quantify the analgesic effects of the compounds [00196]; acetic acid-induced abdominal writhing assay [00197] and tail-flick assay [00198]. As noted by Applicant in the response citing paragraphs [0111] and [0112] as support for the limitation assessing the intensity of the pain in the subject, which disclose antinociception assessment using two pain models, the tail flick and acetic acid writhing assays, quantifying the analgesic effects of the compounds utilizing the tail flick and acetic acid writhing assays reads on assessing the intensity of the pain in the subject.
Regarding the limitation administering a therapeutic amount of a composition comprising SRP-001 or a pharmaceutically acceptable salt thereof at equimolar dosing relative to acetaminophen (ApAP), instant claim 3, which depends from and thus further limits the limitations of claim 1, recites wherein the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject. Bazan ‘122 teaches the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject (claim 39).
MPEP 2131.03 states:
"[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)).
Regarding the limitation wherein SRP 001 achieves a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay, Bazan ‘122 teaches a method of ameliorating pain in a subject comprising administering to said subject afflicted with pain a therapeutically effective amount of SRP-001 in amounts that anticipate the instantly claimed amounts. Moreover, Bazan ‘122 teaches two different assays were utilized to quantify the analgesic effects of the compounds [00196]; acetic acid-induced abdominal writhing assay [00197] and tail-flick assay [00198] in male mice. In performing the active step (i.e. administering an effective amount of the composition comprising SRP-001 taught by Bazan ‘122 to a subject with pain and assessing the pain with the assays taught by Bazan ‘122), the SRP 001 would necessarily result in a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay.
In regard to "wherein” clauses, MPEP 2111.04 states:
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. In the instant case, the wherein clause is directed to the intended result (i.e. achieving a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay) of the process step positively recited (i.e. administering SRP-001 to a subject suffering from pain in an in vivo assay such as tail-flic or acetic acid-induced writhing).
Regarding claim 2, Bazan ‘122 teaches the term “pain” can refer to all types of pain; the term can refer to visceral pain; the term can also refer to nociceptive pain or nociception, such as somatic pain (normal nerve response to a noxious pain) [0088].
Regarding claim 3, Bazan ‘122 teaches the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject (claim 39).
Regarding claim 4, Bazan ‘122 teaches the composition is administered in a single dose (claim 42).
Regarding claim 5, Bazan ‘122 teaches the composition is administered at intervals of about 4 hours, 12 hours or 24 hours (claim 43).
Regarding claim 6, Bazan ‘122 teaches the composition is administered orally , parentally, transdermally, or nasally (claim 44).
Regarding claim 7, Bazan ‘122 as an exemplary embodiment, pharmaceutical combinations of the invention can be administered orally, either in the form of tablets containing excipients such as starch or lactose, or in capsules, either alone or mixed with excipients, or in the form of syrups or suspensions containing coloring or flavoring agents [00118].
Regarding claim 15, Bazan ‘122 teaches the composition is administered in the form of a pill, capsule, cream, spray, lotion, or aqueous solution (claim 45).
Regarding claim 17, Bazan ‘122 teaches the composition exhibits analgesia, antipyresis, or a combination thereof (claim 46).
Regarding claim 18, Bazan ‘122 teaches the composition reduces the risk of hepatotoxicity by at least about 20% (claim 47).
Regarding claim 19, Bazan ‘122 teaches wherein the composition is not metabolized to NAPQI (claim 49).
Regarding claim 20, the prior art does not explicitly teach the specific neuronal target of the composition is one or more of CB1, FAAH or TRPV1, which underlies the analgesia; or wherein SRP-001 has a half-life in said subject of about 4.9 to about 9.8 hours; or wherein in a direct comparison of SRP-001 vs. ApAP at equimolar doses reveals no mortality for SRP-001,whereas ApAP shows a dose-dependent increase in mortality. However, the above pharmacokinetic parameters depend, among other things, from the specific components, relative amounts, type of formulation, and pH of the formulation etc., all of which seem to be the same or very similar to the composition taught by the prior art (see above rejection).
The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the formulations if SRP-001 that will result from the teachings of the prior art does not possess the same material, structural and functional characteristics of the formulation claimed in the instant application. In the absence of evidence to the contrary, the burden is on the applicant to prove that the formulation used in the instantly claimed method is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Thus, the teachings of Bazan ‘122 anticipate the method of instant claims 1-7, 15, and 17-20.
Response to Arguments
Applicant argues:
Amended claim 1 now requires that the method be performed by administering a therapeutic amount of a composition comprising SRP-001 or a pharmaceutically acceptable salt thereof at equimolar dosing relative to acetaminophen (ApAP), wherein SRP-001 achieves a statistically lower ED50 (p < 0.05) than ApAP in at least one validated human pain assay that is an established clinical analogue of a specified in vivo animal assay (e.g., electronic von Frey in young males, tail-flick in aged males, acetic acid writhing, etc.). Bazan '122 does not disclose, expressly or inherently, this feature of amended claim 1.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, instant claim 3, which depends from and thus further limits the limitations of claim 1, recites wherein the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject. Bazan ‘122 teaches the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject (claim 39). The amounts taught by Bazan ‘122 meet the amounts taught by the instant specification. Thus, the amounts taught by Bazan ‘122 would anticipate the instantly claimed therapeutic amount at equimolar dosing relative to ApAP.
Moreover, as set forth above, Bazan ‘122 teaches two different assays were utilized to quantify the analgesic effects of the compounds; acetic acid-induced abdominal writhing assay and tail-flick assay in male mice. In performing the active step (i.e. administering an effective amount of the composition comprising SRP-001 taught by Bazan ‘122 to a subject with pain and assessing the pain with the assays taught by Bazan ‘122), the SRP 001 would necessarily result in a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay.
The wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). In the instant case, the wherein clause is directed to the intended result (i.e. achieving a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay) of the process step positively recited (i.e. administering SRP-001 to a subject suffering from pain in an in vivo assay such as tail-flick or acetic acid-induced writhing).
Applicant argues:
The present application provides direct and unexpected evidence that in the specified models and cohorts, SRP-001 achieves a statistically lower ED50 than ApAP at equimolar dosing. The amended claims further require that SRP-001 induces analgesia by generating a greater amount of arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) compared to an equivalent amount of ApAP. Bazan '122 is silent as to these clinical analogues and does not provide any data or suggestion as to their comparative outcomes.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
MPEP 2131.04 states:
Evidence of secondary considerations, such as unexpected results or commercial success, is irrelevant to 35 U.S.C. 102 rejections and thus cannot overcome a rejection so based. In re Wiggins, 488 F.2d 538, 543, 179 USPQ 421, 425 (CCPA 1973). Thus, arguments regarding unexpected evidence is not found persuasive. Moreover, with regard to the argument that the claims require SRP-001 induces analgesia by generating a greater amount of arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) compared to an equivalent amount of ApAP, as set forth above, a chemical composition and its properties are inseparable. Thus, in practicing the methods of Bazan ‘122, (i.e. administering SRP-001 to ameliorate pain), SRP-001 would possess the characteristic of inducing analgesia by generating N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject. 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 includes functions and/or properties 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 to be shown in the prior art does not possess the characteristic relied on" (205 USPQ 594, second column, first full paragraph). There is no requirement that a person of ordinary skill in the art would have recognized the newly cited function and/or property at the time of invention, so long as the function and/or property can be demonstrated to be reasonably expected to be present. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention"). Applicant has not provided sufficient evidence that the SRP-001 administered in the prior art, assessed in the same or very similar tail-flick and acetic acid-induced writhing assays, would not result in generating a greater amount of arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) compared to an equivalent amount of ApAP.
Applicant argues:
The present claims are drawn to a new, functional dosing method-one that requires comparative, head-to-head equivalence to ApAP for pain relief-not to an inherent property of SRP-001 or its analogs. Because the cited art does not disclose, suggest, or require this dosing methodology, nor does it inevitably result from practicing the cited art, inherency cannot apply.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, Bazan ‘122 teaches a method of treating pain comprising administering SRP-001 in amounts that anticipate the instantly claimed amounts and assessing efficacy in tail-flick and acetic acid-induced writhing assays. Thus, the cited art teaches administering the same compound to the same subjects and assaying efficacy of treatment with the same assays. Thus, the method of the cited art would result performing the same steps with the same drug and thus anticipates the instantly claimed method.
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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Bazan et al (WO 2024/191741 A1, cited in the IDS filed April 30, 2025, published September 19, 2024 and effective filing date March 10, 2023, herein after referred to as Bazan ‘741) in view of Bazan et al (WO 2019/040122 A1, cited in the IDS filed April 30, 2025, hereinafter referred to as Bazan ‘122).
Regarding claim 1, Bazan ‘741 teaches a method for ameliorating pain in a subject in need thereof comprising administering a compound of Formula (I) to the subject, the thereby ameliorate pain (claim 33); a compound of Formula (I) (claim 20):
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This compound reads on SRP-001 as evidenced by the instant specification (see paragraph [0059]).
Although the reference does not specifically identify that SRP-001 induces analgesia by generating a greater amount of N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject compared to an equivalent amount of ApAP, the method steps are the same. A chemical composition and its properties are inseparable. Thus, in practicing the methods of Bazan ‘741, (i.e. administering SRP-001 to ameliorate pain), SRP-001 would possess the characteristic of inducing analgesia by generating N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject. 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 includes functions and/or properties 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 to be shown in the prior art does not possess the characteristic relied on" (205 USPQ 594, second column, first full paragraph). There is no requirement that a person of ordinary skill in the art would have recognized the newly cited function and/or property at the time of invention, so long as the function and/or property can be demonstrated to be reasonably expected to be present. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention").
Regarding the limitation assessing the intensity of the pain in the subject, Bazan ‘741 does not explicitly teach assessing the intensity of pain in the subject. However, Bazan ‘122 teaches two different assays were utilized to quantify the analgesic effects of the compounds [00196]; acetic acid-induced abdominal writhing assay [00197] and tail-flick assay [00198]. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to assess analgesic effect or nociception of SRP-001 in the method disclosed by Bazan ‘741 utilizing acetic acid-induced abdominal writhing assay, since the prior art teaches these are useful methods to determine efficacy of compounds for treating pain.
Regarding the limitation administering a therapeutic amount of a composition comprising SRP-001 or a pharmaceutically acceptable salt thereof at equimolar dosing relative to acetaminophen (ApAP), instant claim 3, which depends from and thus further limits the limitations of claim 1, recites wherein the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject. Bazan ‘122 teaches the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject (claim 39). MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Regarding the limitation wherein SRP 001 achieves a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay, the combination of Bazan ‘741 and Bazan ‘122 teaches a method of ameliorating pain in a subject comprising administering to said subject afflicted with pain a therapeutically effective amount of SRP-001 in amounts that render the instantly claimed amounts obvious where subjects are assayed in tail-flick and acetic acid-induced writhing assays. In performing the active step (i.e. administering an effective amount of the composition comprising SRP-001 taught by Bazan ‘122 to a subject with pain and assessing the pain with the assays taught by Bazan ‘122), the SRP 001 would necessarily result in a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay.
In regard to "wherein” clauses, MPEP 2111.04 states:
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. In the instant case, the wherein clause is directed to the intended result (i.e. achieving a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay) of the process step positively recited (i.e. administering SRP-001 to a subject suffering from pain in an in vivo assay such as tail-flic or acetic acid-induced writhing).
Regarding claim 2, Bazan ‘741 teaches the compounds and formulations are useful in treating acute, chronic, and/or neuropathic pain [0117]. Bazan ‘122 teaches the term “pain” can refer to all types of pain; the term can refer to visceral pain; the term can also refer to nociceptive pain or nociception, such as somatic pain (normal nerve response to a noxious pain) [0088]. Thus, the cited art teaches SRP-100 is suitable for treating visceral and somatic nociception pain.
Regarding claim 4, Bazan ‘741 teaches single oral administration of SRP-3D powder in gelatin capsules [0271].
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(Fig 1).
Regarding claim 5, Bazan ‘741 teaches oral administration of an SRP-3D (DA) nanoparticle suspension three times daily 4 hours apart [0272].
Regarding claim 6, Bazan ‘741 teaches oral administration of SRP-3D ([0271] and [0272]).
Regarding claims 7 and 16, Bazan ‘741 teaches a stable SRP-3D (DA) nanoparticle composition comprising (a) particles of SRP-3D (DA) or a salt thereof and (b) at least one wetting agent, wherein the SRP-3D (DA) particles have an average particle size of less than about 500 nm or less than about 300 nm (claim 1); wherein the composition further comprises one or more pharmaceutically acceptable excipients, carriers, or a combination thereof (claim 6).
Regarding claim 8, Bazan ‘741 teaches the SRP-3D (DA) is present in an amount which is a member selected from the group consisting of from about 99.5% to about 0.001%, from about 95% to about 0.1%, and from about 90% to about 0.5%, by weight, based on the total combined dry weight of the SRP-3D (DA) and at least one wetting agent, not including other excipients (claim 7).
Regarding claim 9, Bazan ‘741 teaches the at least one wetting agent is present in an amount which is a member selected from the group consisting of from about 0.01% to about 99.5% by weight, from about 0.1% to about 95% by weight, and from about 0.5% to about 90% by weight, and from about 0.5 % to about 2%, based on the total combined dry weight of SRP-3D (DA) and at least one wetting agent, not including other excipients (claim 8).
Regarding claim 10, Bazan ‘741 teaches the at least one wetting agent is present in an amount which is a member selected from the group consisting of less than about 10%, less than about 5%, less than about 2% and less than about 1%, based on the weight of the nanoparticulate composition (claim 9).
Regarding claim 11, Bazan ‘741 teaches the at least one wetting agent is a member selected from the group consisting of a bile salt and an alkali salt of a bile acid (claim 11).
Regarding claim 12, Bazan ‘741 teaches the bile salt is a member selected from the group consisting of sodium, potassium, lithium, calcium, arginine, lysine and ammonium salt of a bile acid (claim 11).
Regarding claim 13, Bazan ‘741 teaches a salt of a bile acid which is a member selected from the group consisting of cholic acid, glycocholic acid, taurocholic acid, deoxycholic acid, glycodeoxycholic acid, taurodeoxycholic acid, chenodeoxycholic acid glycochenoxydeoxycholic acid and taurochenoxydeoxycholic acid (claim 12).
Regarding claim 14, Bazan ‘741 teaches the composition further comprising a secondary wetting agent which is a member selected from the group consisting of polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, and cellulose derivatives (claim 13).
Regarding claim 15, Bazan ‘741 teaches SRP-3D powder in gelatin capsules [0271].
With regard to claims 17-19, the wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). In the instant case, the wherein clause is directed to the intended result (i.e. exhibiting analgesia, antipyresis, or a combination thereof (instant claim 17); reducing the risk of hepatoxicity by at least about 20% compared to acetaminophen (ApAP) (instant claim 18); or does not generate the hepatoxic metabolite NAPQI (instant claim 19) of the process step positively recited (i.e. administering SRP-001 to treat pain).
Regarding claim 20, the prior art does not explicitly teach the specific neuronal target of the composition is one or more of CB1, FAAH or TRPV1, which underlies the analgesia; or wherein SRP-001 has a half-life in said subject of about 4.9 to about 9.8 hours; or wherein in a direct comparison of SRP-001 vs. ApAP at equimolar doses reveals no mortality for SRP-001,whereas ApAP shows a dose-dependent increase in mortality. However, the above pharmacokinetic parameters depend, among other things, from the specific components, relative amounts, type of formulation, and pH of the formulation etc., all of which seem to be the same or very similar to the composition taught by the prior art (see above rejection).
The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the formulations if SRP-001 that will result from the teachings of the prior art does not possess the same material, structural and functional characteristics of the formulation claimed in the instant application. In the absence of evidence to the contrary, the burden is on the applicant to prove that the formulation used in the instantly claimed method is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Taken together, all this would result in the practice of the method of claims 1-20 with a reasonable expectation of success.
Response to Arguments
Applicant argues:
The amended claims recite non-obvious, unexpected results. Neither Bazan '741 nor Bazan '122 teaches, suggests, or motivates administering SRP-001 at a therapeutic amount less than or equivalent to ApAP for the same pain intensity, nor do they require or disclose statistically significant, head-to-head comparative ED50 data in the claimed models or clinical analogues. The cited art merely discloses that SRP-001 is "effective" for pain, not that it achieves efficacy at a dose less than or equivalent to ApAP, let alone with statistically significant superiority in specified models/cohorts/specific pain and populations.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, both Bazan ‘741 and Bazan ‘122 teach SRP-001 is useful for treating pain. Bazan ‘122 denotes SRP-001 as SRP6D (page 52, 4th compound). Moreover, Bazan ‘122 teaches in two different in vivo analgesia mouse models, acetic acid-induced abdominal writhing and the tail flick assays, SRP6D and R are comparable to ApAP (FIG. 1) [00216]. Thus, Bazan ‘122 explicitly teaches comparing data from SRP-001 and ApAP in acetic acid-induced abdominal writhing and the tail flick assays. Moreover, Bazan ‘122 discloses the following data for the tail flick test, wherein SRP6D results in increased latency and increased maximum analgesia (Fig 1):
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Thus, it is not unexpected that SRP6D/SRP-001 would have comparable or improved antinociception efficacy compared to ApAP. MPEP 716.02(c).II. states:
"Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967) (resultant decrease of dental enamel solubility accomplished by adding an acidic buffering agent to a fluoride containing dentifrice was expected based on the teaching of the prior art); Ex parte Blanc, 13 USPQ2d 1383 (Bd. Pat. App. & Inter. 1989). Thus, the data provided are insufficient to rebut the prima facie case of obviousness.
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 1-7, 15, and 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 7, and 10-23 of U.S. Patent No. 11,458,142 B2 in view of Bazan et al (WO 2019/040122 A1, cited in the IDS filed April 30, 2025, hereinafter referred to as Bazan ‘122).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The present claims are directed to a method for ameliorating a pain in a subject in need thereof comprising administering a therapeutic amount of a composition comprising SRP-001 or a pharmaceutically acceptable salt thereof, wherein SRP-001 induces analgesia by generating N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject, to thereby ameliorate the pain.
The previously allowed claims are directed to a method of ameliorating pain in a subject comprising administering to said subject afflicted with pain a therapeutically effective amount of the analgesic composition of formula (I) wherein the composition of formula (I) has the structure:
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This compound reads on SRP-001 as evidenced by the instant specification (see paragraph [0059]).
Although the previously allowed claims do not specifically identify analgesia by generating a greater amount of N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject compared to an equivalent amount of ApAP, the method steps are the same. A chemical composition and its properties are inseparable. Thus, in practicing the methods of previously allowed claims, (i.e. administering SRP-001 to ameliorate pain), SRP-001 would possess the characteristic of inducing analgesia by generating N-arachidonoylphenolamine (AM404) in the midbrain periaqueductal gray (PAG) of the subject. 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 includes functions and/or properties 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 to be shown in the prior art does not possess the characteristic relied on" (205 USPQ 594, second column, first full paragraph). There is no requirement that a person of ordinary skill in the art would have recognized the newly cited function and/or property at the time of invention, so long as the function and/or property can be demonstrated to be reasonably expected to be present. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) ("[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention").
Regarding the limitation assessing the intensity of the pain in the subject, although the previously allowed claims do not explicitly teach assessing the intensity of pain in the subject. However, Bazan ‘122 teaches two different assays were utilized to quantify the analgesic effects of the compounds [00196]; acetic acid-induced abdominal writhing assay [00197] and tail-flick assay [00198]. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to assess analgesic effect or nociception of SRP-001 in the method of the previously allowed claims utilizing acetic acid-induced abdominal writhing assay, since the prior art teaches these are useful methods to determine efficacy of compounds for treating pain.
Regarding the limitation wherein the therapeutic amount of SRP-001 is less than or equivalent to a dose of acetaminophen (ApAP) effective to treat the pain intensity of the subject, instant claim 3, which depends from and thus further limits the limitations of claim 1, recites wherein the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject. The previously allowed claims are directed to wherein the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM. MPEP 2131.03 states:
"[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)).
Regarding the limitation wherein SRP 001 achieves a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay, the previously allowed claims and Bazan ‘122 teach a method of ameliorating pain in a subject comprising administering to said subject afflicted with pain a therapeutically effective amount of SRP-001 in amounts that render the instantly claimed amounts obvious where subjects are assayed in tail-flick and acetic acid-induced writhing assays. In performing the active step (i.e. administering an effective amount of the composition comprising SRP-001 taught by Bazan ‘122 to a subject with pain and assessing the pain with the assays taught by Bazan ‘122), the SRP 001 would necessarily result in a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay.
In regard to "wherein” clauses, MPEP 2111.04 states:
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 283 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a “wherein” clause limited a process claim where the clause gave “meaning and purpose to the manipulative steps”). In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. In the instant case, the wherein clause is directed to the intended result (i.e. achieving a statistically lower ED 50 (p ≤ 0.05) than ApAP in at least one in vivo assay) of the process step positively recited (i.e. administering SRP-001 to a subject suffering from pain in an in vivo assay such as tail-flic or acetic acid-induced writhing).
Furthermore, the previously allowed claims are directed to wherein pain is nociceptive pain; the therapeutically effective amount comprises a dose of about 10 µM to about 10 mM of the composition is administered to the subject; the composition is administered in a single dose; the composition is administered at intervals of about 4 hours, 12 hours or 24 hours; the composition is administered orally , parentally, transdermally, or nasally; the composition is administered in the form of a pill, capsule, cream, spray, lotion, or aqueous solution; the composition exhibits analgesia, antipyresis, or a combination thereof; the composition reduces the risk of hepatotoxicity by at least about 20%; and the composition is not metabolized to NAPQI.
Moreover, the previously allowed claims are directed a composition administered in the form of an aqueous solution. This reads on a composition comprising an excipient, wherein the excipient is water.
Regarding claim 20, the previously allowed claims do not explicitly teach the specific neuronal target of the composition is one or more of CB1, FAAH or TRPV1, which underlies the analgesia; or wherein SRP-001 has a half-life in said subject of about 4.9 to about 9.8 hours; or wherein in a direct comparison of SRP-001 vs. ApAP at equimolar doses reveals no mortality for SRP-001,whereas ApAP shows a dose-dependent increase in mortality. However, the above pharmacokinetic parameters depend, among other things, from the specific components, relative amounts, type of formulation, and pH of the formulation etc., all of which seem to be the same or very similar to the composition taught by the prior art (see above rejection).
The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the formulations if SRP-001 that will result from the teachings of the prior art does not possess the same material, structural and functional characteristics of the formulation claimed in the instant application. In the absence of evidence to the contrary, the burden is on the applicant to prove that the formulation used in the instantly claimed method is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Thus, It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to arrive at the method of the instant claims from the method of the previously allowed claims.
Response to Arguments
Applicant argues:
US '142 does not provide direct, quantitative, head-to-head ED50 data or comparative AM404 data to allow for the precise dose as is currently claimed. There is no requirement, disclosure, or demonstration that SRP-001's effective dose is less than or equivalent to ApAP's for a given pain intensity. There is no explicit or implicit teaching of dose equivalence, head-to-head potency determination, or selection of dose based on ApAP's effective dose.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to assess analgesic effect or nociception of SRP-001 in the method of the previously allowed claims utilizing acetic acid-induced abdominal writhing assay, since the prior art teaches these are useful methods to determine efficacy of compounds for treating pain. Moreover, Bazan ‘122 teaches in two different in vivo analgesia mouse models, acetic acid-induced abdominal writhing and the tail flick assays, SRP6D and R are comparable to ApAP (FIG. 1) [00216]. Thus, Bazan ‘122 explicitly teaches comparing data from SRP-001 and ApAP in acetic acid-induced abdominal writhing and the tail flick assays. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to assess analgesic effect or nociception of SRP-001 in the method of the previously allowed claims utilizing acetic acid-induced abdominal writhing assay, since the prior art teaches these are useful methods to determine efficacy of compounds for treating pain.
Conclusion
Claims 1-20 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628