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 .
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.
This office action is a response to applicant’s communication submitted October 25, 2023, wherein claims 1-2, 5-7, 12-13, 18, 24, 27, 31, 41, and 46-48 were preliminarily amended, and claims 3-4, 8-10, 14-16, 19-23, 26, 28-30, 32-40, 42-45, and 49 were canceled.
Claims 1-2, 5-7, 11-13, 17-18, 24-25, 27, 31, 41 and 46-48 are pending in this application.
Priority
This application is a 371 of PCT/US2021/055212 filed October 15, 2021 and claims benefit to provisional US application 63/092,295 filed October 15, 2020. Provisional US application 63/092,295 filed October 15, 2020 does not provide written description for the present claims under 35 USC 112(a). In particular, this application only supports wherein STING agonists mixed with the one or metal ions are associated with polyhistidine or polyhistidinePEG (wherein PEG is a specific glycol), not any poly(histidine)-glycol moiety as recited by instant claim 1. Therefore the effective filing date of present claims 1-2, 5-7, 11-13, 17-18, 24-25, 27, 31, 41 and 46-48 is the filing date of the instant application, filed April 13, 2023. Claims 2 and 6 do find support in the provisional application and thus have an effective filing date of October 15, 2020.
Drawings
The drawings are objected to because:
The structures and respective subscripts in figures 1-7 blurry/unclear.
Figure 11a metal ions are illegible.
Figure 12d axis labels are illegible.
Figure 14b axis labels are illegible.
The top left image in figure 15 is illegible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
On page 26, the following structures blurry and have unclear/overlapping bond lines:
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and should be clarified (lines 1-5).
Appropriate correction is required.
Claim Objections
Claims 1, 7, 25, 46-47 are objected to because of the following informalities:
Claim 1 should define the acronym STING the first time it appears.
Claim 7 structures STING-agonist-C11, STING agonist-1 and STING agonist G10 are unclear.
Claim 25 recites the phrase “Derivaed” which should read “Derived”.
Claim 46is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1, as merely reciting an intended use does not result in a different composition. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 47 recites a series of formulations and at the end recites “and/or suppository”, which should read “or suppository” as it is a list of alternatives.
Appropriate correction is required.
Claim Interpretation
With respect to instant claim 46, which is directed to a pharmaceutical composition and recites the phrase “analgesic pharmaceutical composition for use in treating pain”. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “for use in treating pain” will not further limit claims drawn to a composition, so long as the prior art discloses the same composition comprising the same ingredients in an effective amount, as the instantly claimed (See MPEP 2111.02 (II)).
Claim Rejections - 35 USC § 112 (a) New Matter
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 1, 5, 11-13, 17-18, 24-25, 27, 31, 41, 46-48 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claims 1, 5, 11-13, 17-18, 24-25, 27, 31, 41, 46-48: Claim 1 was amended to include new subject matter that was not present in the instant specification or priority documents. Provisional US application 63/092,295 filed October 15, 2020 does not provide written description for the present claims under 35 USC 112(a). In particular, this application only supports wherein STING agonists mixed with the one or metal ions are associated with polyhistidine or polyhistidinePEG (wherein PEG is a specific glycol), not any poly(histidine)-glycol (glycol is much broader) moiety as recited by instant claim 1.
Claim Rejections - 35 USC § 112 (a) Written Description
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 1-2, 5-7, 11-13, 17-18, 24-25, 27, 31, 41, 46-48 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims require “crystalline polymorphic forms of one or more STING agonists”. The claims do not require that the crystalline polymorphic STING agonist possess any particular conserved structure, or other distinguishing feature. The instant specification has demonstrated a single compound, c-di-AMP (CDA) forms different polymorphic forms with specific metal ions (pg. 18, figure 1, drawings figure 1, pg. 68, lines 15-25, example I). Thus, the claims are drawn to a genus of compounds that is defined by novelty.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 [10 USPQ2d 1614] (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”). Thus, an applicant complies with the written-description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572.
According to the MPEP §2163 I. A. “the issue of a lack of adequate written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant had possession of the claimed invention. The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.” The MPEP states in §2163 II 3 ii) “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
According to the MPEP §2163.02 Standard for Determining Compliance With the Written Description Requirement,
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed". In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon “reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter". Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
This case was filed before Applicants had a clear idea of the structures of their desired compounds, how to make their compounds and how to use them.
Applicants are reminded of what the U.S. Court of Appeals Federal Circuit wrote in University of California v. Eli Lilly and Co. 43 USPQ2d 1398, "In claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate description of the claimed genus." "A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is.” See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). "It is only a definition of a useful result rather than a definition of what achieves that result." "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.")".
Therefore, the full breadth of the claim fails to meet the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision.
Claim Rejections - 35 USC § 112 (a) Enablement
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 1-2, 5-7, 11-13, 17-18, 24-25, 27, 31, 41, 46-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for crystalline polymorphic forms of cdiAMP, does not reasonably provide enablement for crystalline polymorphic forms of all STING agonists. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)).
These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4)
relative skill in the art; (5) amount of direction provided by the inventor; (6) the level of
predictability in the art; (7) the existence of working examples; and (8) quantity of
experimentation needed to make or use the invention based on the content of the disclosure. All
of the factors have been considered with regard to the claim, with the most relevant factors
discussed below:
(1& 2) The breadth of the claims and nature of the invention: The claims are drawn to compositions comprising crystalline polymorphic forms of STING agonists associated with a poly(histidine)-glycol moiety and methods of treating/preventing/ameliorating diseases via administration of said composition.
(3) The state of the prior art: There is prior art that teaches pharmaceutical compounds can be made into polymorphs. For example, Healy et al (Advanced Drug Delivery Reviews, 2017, cited on PTO-892) teaches active pharmaceutical ingredients (APIs) may exist in various solid forms and differences in solid forms often lead to differences in thermodynamic parameters and physicochemical properties for example solubility, dissolution rate, stability and mechanical properties of APIs (abstract). The fundamental characteristics and trends observed for pharmaceutical hydrates, solvates and amorphous forms are presented, with special emphasis, due to their relative abundance, on pharmaceutical hydrates with single and two-component (i.e. cocrystal) host molecules (abstract). However, Healy teaches that there are various means by which solvent can be associated with crystalline solids: adsorption on a solid surface, adsorption and absorption into disordered regions and crystal defects, the physical inclusion of liquid during crystal growth, and solvent associated as part of crystal packing (pg. 27, section 2.1). Pharmaceutical APIs, and their mixtures/formulations can be processed by different techniques, including solvent-based and fusion-based methods (pg. 39, section 3.3). Different manufacturing methods can lead to different solid forms of single and multicomponent systems (pg. 39, section 3.3). The characterization of different solid-state forms of APIs - solvates, hydrates, and amorphous forms - is pivotal in early-stage solid form screening during drug product development, not just for single component systems, but also for two component systems (pg. 42, section 5).
Additionally, Censi (Molecules, 2015, IDS filed November 4, 2024) teaches drugs with low water solubility can be improved by formulating into polymorphs (abstract). Censi teaches crystalline polymorphs have the same chemical composition, but different internal crystal structures, and therefore possess different physicochemical properties (pg. 18761, last para.). However, Censi teaches polymorphs can be a challenge to ensure physicochemical stability and can be less stable compared to the original form (abstract, pg. 18762, para. 3).
Thus, in short, the art recognizes polymorphs of compounds can be made but can take on different forms with different properties and may be unstable, requiring extensive characterization.
(4) The level of skill in the art: The level of skill in the art would be high, mostly likely at
the Ph.D. /MD level.
(5 & 7) The amount of direction provided by the inventor and the existence of working
examples: Applicant has not provided sufficient examples to demonstrate crystalline polymorphic forms can be formed across the claimed genus of compounds with the claimed metal ions. The instant specification has demonstrated a single compound, c-di-AMP (CDA) forms different polymorphic forms with specific metal ions (pg. 18, figure 1, drawings figure 1, pg. 68, lines 15-25, example I).
(6) The level of predictability in the art: The prior art does not teach a method of preparing all STING agonists into crystalline polymorphic forms with metal ions. There are not any clear, routine teachings in the art that would enable all the compounds claimed to be prepared as crystalline polymorphs. There is no evidence in the prior art that all the claimed STING agonists are capable of existing as stable crystalline polymorphs.
(8) The quantity of experimentation necessary: Neither the instant specification nor the state of the art have demonstrated how all the compounds claimed can be made into as crystalline polymorphs.
In order to translate the compounds in Applicant’s disclosure into a crystalline polymorphs one skilled in the art would have to develop a crystallization method and use advanced analytical techniques to characterize the properties of the compounds crystalline. As discussed with Healy and Censi, differences in solid forms often lead to differences in thermodynamic parameters and physicochemical properties for example solubility, dissolution rate, stability and mechanical properties of APIs.
Therefore, other than proposing an initial hypothesis, the entire burden of research involved in developing crystalline polymorphic forms of the compounds claimed would fall on the shoulders of the skilled artisan attempting to practice the claimed invention, presenting an undue burden of unpredictable experimentation.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a
reward for search, but compensation for its successful conclusion.” And “patent protection is
granted in return for an enabling disclosure of an invention, not for vague intimations of general
ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, Applicant fails to provide information sufficient to practice the claimed invention without undue experimentation.
Claims 12-13, 17-18, 24-25, 27, 31, 41, 46-48 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The specification, while being enabling for cancer immunotherapy via stimulation of an immune response and a vaccine adjuvant for Covid 19 with a specific composition, does not reasonably provide enablement for the treatment/prevention/prophylaxis/ameliorating of all diseases as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most clear connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)).
These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4)
relative skill in the art; (5) amount of direction provided by the inventor; (6) the level of
predictability in the art; (7) the existence of working examples; and (8) quantity of
experimentation needed to make or use the invention based on the content of the disclosure. All
of the factors have been considered with regard to the claim, with the most relevant factors
discussed below:
(1& 2) The breadth of the claims and nature of the invention: The claims are drawn to compositions comprising crystalline polymorphic forms of STING agonists associated with a poly(histidine)-glycol moiety and methods of treating/preventing/ameliorating diseases including cancer, infection, respiratory diseases as well as acting as an analgesic via administration of said composition.
(3) The state of the prior art: While there are publications that describe therapeutic potential in treating cancer, infections, respiratory diseases with STING agonists, there is no evidence in the prior art that the claimed compositions would treatment/prevention/prophylaxis/ ameliorating of all diseases/conditions as claimed. For example Moura Rodriguez (Cells, 2022, cited on PTO-892) teaches STING agonists have potential therapeutic benefits in the context of respiratory diseases, as antiviral adjuvants, and can possess antiviral properties against SARS-CoV-2 (abstract). Moura Rodriguez teaches that structure of STING agonists can affect its purpose,. (pg. 4, 2.1, pg. 5, 2.2). wherein cyclic dinucleotide STING agonists can stimulate innate immune response and treat infections (pg. 4, paras. 1 and 3). Non nucleotide based STING agonists can elicit strong antitumor activity (pg. 5, para. 3). Additionally, Wang (Nature Communications, 2021, cited on PTO-892) discloses STING agonism may be beneficial in treating bone cancer pain, but it remains unclear whether STING agonists are effective in treating bone cancer pain (analgesic, abstract, pg. 2, col. 1, para. 2). Censi (Molecules, 2015, IDS filed November 4, 2024) teaches drugs with low water solubility can be improved by formulating into polymorphs (abstract). Censi teaches crystalline polymorphs have the same chemical composition, but different internal crystal structures, and therefore possess different physicochemical properties (pg. 18761, last para.). However, Censi teaches polymorphs can be a challenge to ensure physicochemical stability and can be less stable compared to the original form (abstract, pg. 18762, para. 3). Censi teaches that different polymorphic forms can have varying clinical efficacies (pg. 18760, paras. 2-3). Thus, in short, the art recognizes administering therapeutic compositions containing STING agonists can treat specific cancers, infections, and ameliorate pain, but there is no evidence in the prior art that compositions comprising STING agonists, such as the compositions claimed are capable of treatment/prevention/prophylaxis/ameliorating of all diseases/conditions as claimed. The art further recognizes that polymorphic forms of drugs can be unstable for therapeutic purposes. Additionally, wherein the art establishes that polymorphic forms of a given agent can significantly alter therapeutic potential of a given drug, there is no general teaching that crystalline polymorphic forms of all STING agonists claimed are effective at treating all the claimed diseases.
(4) The level of skill in the art: The level of skill in the art would be high, mostly likely at
the Ph.D. /MD level.
(5 & 7) The amount of direction provided by the inventor and the existence of working
examples: Applicant has not provided examples that demonstrate treatment/prevention/prophylaxis/ ameliorating of all diseases/conditions with the claimed compositions. The instant specification has demonstrated a single compound, c-di-AMP (CDA) forms different polymorphic forms with specific metal ions (pg. 18, figure 1, drawings figure 1, pg. 68, lines 15-25, example I). The instant specification demonstrates that a single crystalline polymorph may stimulate immune response in cancer immunotherapy (pg. 74, lines 12-23). The instant specification demonstrates that a single crystalline polymorph may serve as a potent vaccine adjuvant platform for COVID-19 vaccine (pg. 75, lines 16-33).
(6) The level of predictability in the art: The prior art does not teach a method of treatment/prevention/prophylaxis/ameliorating of all diseases/conditions claimed with the claimed compositions comprising crystalline polymorphs of STING agonists. There are not any clear, routine teachings in the art that would enable all the compositions claimed to be prepared as crystalline polymorphs and used for therapeutic purposes of the claimed diseases. There is no evidence in the prior art that treatment of all the diseases with all the claimed compositions is possible, given the lack of a trend associated with polymorphs of STING agonists in treating diseases.
(8) The quantity of experimentation necessary: Neither the instant specification nor the state of the art have demonstrated how compositions, such as the compositions comprising crystalline polymorphs of STING agonists claimed, treatment/prevention/prophylaxis/ ameliorating of all diseases/conditions claimed. An undetermined number of experimental factors utilizing a compound and its method for treating would have to be resolved by the practitioner and/or the patient for the following reasons: the factors are not sufficiently discussed in the specification to provide guidance to utilize the invention as claimed.
Therefore, other than proposing an initial hypothesis, the entire burden of research
involved in utilizing the compositions claimed treatment/prevention/prophylaxis/ ameliorating of all diseases/conditions claimed would fall on the shoulders of the skilled artisan attempting to practice the claimed invention, presenting an undue burden of unpredictable experimentation.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a
reward for search, but compensation for its successful conclusion.” And “patent protection is
granted in return for an enabling disclosure of an invention, not for vague intimations of general
ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, Applicant fails to provide information sufficient to practice the claimed invention without undue experimentation.
Claim Rejections - 35 USC § 112 (b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 5-7, 11-13, 17-18, 24-25, 27, 31, 41 and 46-48 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1: Claim 1 recites the phrase “is associated with”. According to the instant specification, wherein the phrase “is associated with” can for example be complexed, conjugated, encapsulated, absorbed, adsorbed, admixed (pg. 8, lines 16-18). However, exemplification is not an explicit definition. It is unclear what is encompassed by the phrase “is associated with” given the phrase can also be interpreted to include in close proximity to, covalently bound, etc. A person of ordinary skill would be unable to ascertain the metes and bounds of the invention, thereby rendering claim 1 indefinite. Claims 2, 5-7, 11-13, 17-18, 24-25, 27, 31, 41 and 46-48 which depend from claim 1 are similarly rejected.
Regarding claim 2: Claim 2 recites inter alia, “….wherein the poly(histidine) is poly(histidine33) (H33)….. wherein the polyhistidine33 length is between 1-50 repeat units.”. It is unclear whether the claim is in reference to the repeating units of histidine, which is already specified to be 33, or means repeating units of polyhistidine33 (i.e. 33, 66, 99). According to the instant specification the amount of PEG units or histidine units is changed, but not in factors of histidine 33 (drawings figure 4). Thus, the scope of the claim is unclear rendering it indefinite. Claim 6 which depends from claim 2 is similarly rejected.
Claim 6, which depends from claim 2 and recites inter alia, “wherein the concentration of H33-PEG is equal to or more than 1.3 mg/mL within each of the crystalline polymorphic forms of the one or more STING agonists.” However, Claim 1 of which claim 6 ultimately depends merely describes that the polyhistidine glycol moiety is associated with the crystalline polymorphic forms. It is unclear how the polyhistidine can be associated with and within the crystalline form at the same time. Thus, the scope of the claim is rendered indefinite.
Regarding claim 7: Claim 7 recites “SB11285 (Spring Bank pharmaceuticals)”. The phrase in the parenthesis lends doubt as to whether the phrases in parenthesis throughout the claim are meant to describe a product or a source of a product. Thus the scope of the claim is unclear and rendered indefinite.
Regarding claim 7, which recites “,Difluor(RpSp),” positioned between two commas rendering the claim unclear whether this is intended as a specific STING agonist, or is a modification of another STING agonist.
Regarding claim 7: Claim 7 recites a series of structurally diverse compounds followed by “any derivatives thereof” without denoting sufficient structure thereof. Claim 7 recites several compounds followed by the phrase “fluorinated” without denoting fluorination positions. Claim 7 recites several compounds followed by the phrase “-based compounds”. In each scenario, the phrases are unclear in what structural modifications are encompassed and whether these resulting compounds would still be classified as STING agonists. The instant specification provides no standard for determining what constitutes an acceptable derivative, acceptable fluorination position, or a MSA-2-based compound (for example). Thus a person of ordinary skill in the art would be unable to determine the full scope of compounds encompassed by the claim, thereby rendering the claim indefinite.
Regarding claim 11: Claim 11 recites, “The composition of claim 1, wherein the composition is generated via a one-pot reaction.”. The phrase “one-pot reaction” renders the claim indefinite because claim 1 recites “wherein each of the one or more STING agonists mixed with the one or more metal ions is associated with a poly(histidine)-glycol moiety”, implying that the STING agonists are pre-mixed with the metal ion. According to the instant specification, “the term “one-pot synthesis reaction”…. refers to a chemical synthesis method in which all reactants are present in a single vessel.” (pg. 12, lines 30-32). The instant specification also states, “association between a STING agonist and one or more metal ions….resulting in crystalline polymorphic forms of a sting agonist mixed with one or more metal ions is accomplished during a “one-pot reaction” (pg. 12, lines 26-30). The instant specification also states “a one-pot reaction occurs wherein a STING agonist is reacted with one more metal ions in one vessel, such conjugation being facilitated by the additional presence of H33-PEG.” (pgs. 12-13, bridging sentence). Thus it is unclear whether the one-pot refers to the formation of the crystalline polymorph merely with metal ions and STING agonist, or all three components based on the instant specification and lack of clarity of the phrase “is associated with” in claim 1.
Regarding claim 13: Claim 13 recites inter alia, “wherein the administration results in an innate cytokine response mediated through cytokines in the subject, wherein the innate cytokine response is mediated through type 1 interferon.”. The claim is unclear because it is unclear whether the claim is intended to limit claim 12 to a specific method, or is merely describing a property that occurs as a result of practicing said method.
Regarding claims 24-25: Claims 24 recites the phrases “is further associated with” and “configured to target cancer cells.”. Claim 25 recites the phrase “wherein the agent configured to target cancer cells”. According to the instant specification, wherein the phrase “is associated with” can for example be complexed, conjugated, encapsulated, absorbed, adsorbed, admixed (pg. 8, lines 16-18). However, exemplification is not an explicit definition. It is unclear what is encompassed by the phrase “is associated with” given the phrase can also be interpreted to include in close proximity to, covalently bound, etc. Additionally it is unclear whether the phrase “configured to” is meant to describe structure or a product by process. It is unclear what structural changes are required to be considered “configured to”. A person of ordinary skill would be unable to ascertain the metes and bounds of the invention, thereby rendering claim 1 indefinite. It is unclear what constitutes Claim 25 which also recites “configured to” and depends from claim 24 is similarly rejected.
Regarding claim 25: The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Additionally there are multiple uses of parenthesis throughout the claims that make the claim unclear whether the phrases in parenthesis are merely exemplary or describing the specific limitation to be included. For Example, the phrase “(and WT1-derivaed peptide sequences:….” and “(MUC1-derived peptides and glycopeptides…..”
Regarding claim 31: Claim 31 recites inter alia, “a SARS-CoV-2 related viral infection”. The phrase renders the claim indefinite what constitutes a related viral infection (i.e. ancestry, similar action), or whether the claim is merely attempting to state the infection is caused by SARS-CoV-2 virus, or infections other than said SARS-CoV-2 virus.
Regarding claims 46-48: Claim 48 is intended to limit claim 46 by reciting “a therapeutically effective amount is used” for treating and/or preventing pain in a subject. However recitation of this phrase in a dependent claim renders the scope unclear because it is unclear what amounts are encompassed by claim 46 which recites the composition for use in treating pain in a subject. Does this mean a non-therapeutically effective amount is used in the composition of claim 46 for treating pain? The lack of clarity in scope renders claims 46 and 48 indefinite, and claim 47 which depends from claim 46.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 11, 13, and 48 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 11: Claim 11 recites wherein the composition is generated via a one-pot reaction. Number of pots does not materially alter the composition, absent evidence to the contrary. Thus claim 11 fails to further limit claim 1.
Claim 13, which depends from claim 12 and recites, wherein the administration results in an innate cytokine response mediated through cytokines in the subject, wherein the innate cytokine response is mediated through type 1 interferon” does not recite an active step but rather a property that results from practicing the method, thus failing to further limit claim 12
Claim 48, which depends from claim 46, recites inter alia, “is used for treating and/or preventing pain in a subject.”. However, claim 46 only recites “for use in treating pain in a subject…”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5, 7, 11-13, 17-18, 24-25, 27, 41, 46-48 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Moon (WO 202014644, IDS filed November 4, 2024).
Regarding claims 1, 5, 7, 11-12, 46, and 48: Moon teaches methods for stimulating the innate immune response in a subject with agents capable of stimulating an immune response in a subject upon administering to a subject (abstract). Moon teaches that CDNS including cdi-AMP assemble into nanoparticles in the presence of Zn2+ and PEG (pg. 3, lines 2-13). Moon teaches the preparation of CDA-Mn-His33-PEG for injection to stimulate immune response to deliver STING agonist (pg. 4, lines 10-12 Moon teaches the preparation of a composition of coordination formulations comprising Mn2+-CDA/H33-PEG as innate immune stimulators (pg. 105, Example X, lines 25-34, drawings pg. 20, figure 14b). In specific synthesis of STING agonists with metal ions the ratio of metal ions to STING agonist (i.e. CDN) is 10:1 (i.e. greater than 0.1 ,pg. 99, lines 14-21, 23-33). In a specific synthesis, the STING agonist was present in the formulation at a concentration of 1 mg/mL (pg. 101, lines 29-35). Although Moon does not refer to these compounds as crystalline polymorphs, according to the instant specification, the polymorphic forms are formed by merely mixing STING agonists with metal ions at room temperature and adding PEG-polyhistidine in a one-pot synthesis (pg. 68, lines 29-34), which is comparable to method disclosed in the Moon (pg. 102, lines 14-20). Moon teaches that Metal ions-CND/polyhistidine-PEG were prepared by a 1-step precipitation method (i.e. one-pot, pg. 102, lines 14-20). Furthermore, the instant specification describes that mixing STING agonists with Zn2+ and/or Mn2+ crystalline polymorphic forms (e. g., coordinated polymeric forms) capable of assembling into homogeneous and stable nanoparticles in the presence of poly-histidine33-polyethylene glycol (pg. 3, lines 1-4). Figure 11A on page 11 of the drawings demonstrates this one-pot synthesis results in nanoparticles containing the coordinated polymorphs within (drawings, pg. 11, figure 1A). Moon does not use the phrase crystalline directly, however, recites “coordination” throughout the disclosure, as in the phrase “polymer stabilized metal-CDN coordination nanoparticles” or “CDN-metal ion coordination polymers” (pg. 28, lines 9-16, pg. 101, line 29). Wherein the instant specification states that coordinated polymeric forms are an example of crystalline polymorphic forms, and Moon describes “CDN-metal ion coordination polymers”, absent evidence to the contrary, the compositions of the instant claims directed to crystalline polymorphs comprising STING agonists and one or more metal ions associated with polyhistidine-PEG and Moon directed to a composition comprising STING agonists and one or more cations further comprising polyhistidine-PEG both necessarily resulted in crystalline polymorphic forms of STING agonists with metal ions and consequently form nanoparticles in the presence of PEG-polyhistidine.
Regarding claim 13: Moon teaches the innate cytokine response can be mediated through type 1 interferon (pg. 40, lines 19-21).
Regarding claims 17-18, 24-25, 27, and 47: Moon teaches administration via intratumoral injection to mice with colon tumors or melanoma for treatment (pg. 27, lines 13-24, pg. 34, lines 20-27). Moon teaches the composition can be further associated with one or more agents configured to target cancer cells, including cdk4 (pg. 16, lines 3-10). Moon teaches the composition can be administered for prostate cancer treatment, a chemotherapeutic agent, an anti-CTLA-4 antibody (pg. 78, lines 33-34). Moon teaches the composition can be administered via intravenous injection (pg. 79, lines 11-20).
Regarding claim 41: Moon teaches the compositions are intended to be used for administration to a human (pg. 77, lines 18-23).
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.
Claims 5, 41, and 46-48 are rejected under 35 U.S.C. 103 as being unpatentable over Moon (WO 202014644, IDS filed November 4, 2024) as applied to claims 1, 5, 7, 11-13, 17-18, 24-25, 27, 31, 41, 46-48.
Regarding claim 5: As discussed above, Moon teaches the composition of claim 1. Even if assuming for the sake of argument Moon does not teach wherein the STING agonist is present in amount between 0.01 and 5 mg/mL as recited by instant claim 5, instant claim 5 would still have been rendered obvious over Moon.
As discussed above, in a specific synthesis, the STING agonist was present in the formulation at a concentration of 1 mg/mL (pg. 101, lines 29-35). Additionally Moon teaches that the concentration and ratio of metal ion:CDA: polyhistidine-PEG are optimizable variables (pg. 106, lines 1-5). The Examiner notes that generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." (See MPEP 2144.05 (II)).
Taken together it would have been prima facie obvious to optimize the concentration of STING agonist present in the composition as suggested by Moon. A person of ordinary skill in the art would have the motivation to do so given the synthesis involves a stock concentration of STING agonist at 1mg/mL and Moon suggests concentration is a variable to be optimized. Routine optimization would be within the technical grasp of the skilled artisan attempting to improve therapeutic use, absent evidence of criticality of the range not encompassed by the prior art.
Regarding claim 41: As discussed above, Moon teaches the method of claim 12. Even if assuming for the sake of argument Moon does not teach specifically for treatment of a human subject as recited by instant claim 41, instant claim 41 would still have been rendered obvious over Moon as Moon teaches the compositions are intended to be used for administration to a human (pg. 77, lines 18-23).
Regarding claims 46-48: As discussed above, Moon teaches the composition of claim 46. Even if assuming for the sake of argument the claims were to be interpreted in such a way that the intended use limits the claim, and Moon does not teach specifically for use in treating pain in a subject as an analgesic composition as recited by instant claims 46-48, instant claims 46-48 would still have been rendered obvious over Moon.
Moon teaches the composition can be combined with an analgesic, thereby making it an analgesic composition useful for treating pain (pg. 24, lines 10-20, pgs. 89-90, bridging para.).
Taken together it would have been prima facie obvious to combine the composition with a therapeutic amount of an analgesic as suggested by Moon, for analgesic purposes. A person of ordinary skill in the art would have the motivation to do so with a reasonable expectation of success as pain management is a known technique in the treatment of diseases with STING agonists.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Moon (WO 202014644, IDS filed November 4, 2024) as applied to claims 1, 5, 7, 11-13, 17-18, 24-25, 27, 31, 41, 46-48 above in view of Wu (BioRxiv, 2020, cited on PTO-892).
Regarding claim 31: As discussed above, the Moon teaches the method of claim 12. Moon further teaches the STING modulators of the invention can be combined with viral antigens including those of the SARS-coronavirus type (pg. 62, lines 5-15).
Moon does not teach wherein the subject is suffering from or at risk of suffering from conditions and symptoms caused by a SARS-CoV-2 related viral infection, and wherein the administration results in reduced proinflammatory cytokine release by immune effector cells.
However, Wu teaches that STING agonists may be useful as an adjuvant for SARS-CoV-2 vaccine (i.e. subjects at risk, abstract). Wherein STING agonists are recognized for this ability to act as adjuvants, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)).
Taken together, it would have been prima facie obvious to modify Moon such that the composition is administered as an adjuvant to a subject at risk of suffering from a SARS-CoV-2 related infection. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that this is a known technique in the art for STING agonists as vaccine adjuvants, and it is prima facie obvious to substitute one STING agonist composition for another. Although the prior art does not teach wherein the composition results in reduced proinflammatory cytokine release by immune effector cells, wherein it would be obvious to apply the method to SARS-CoV-2 related infection, this property necessarily flows as a result of practicing the method.
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, 2, 5-7, 11, 46, and 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Application 17/259819 (US 20220072023, cited on PTO-892, Notice of Allowance mailed December 18, 2025). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1-2, 5-7, 11, 46, and 48: Copending claim 1 is directed towards a composition comprising a nanoparticle comprising one or more stimulator of interferon genes (STING) agonists and
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wherein the nanoparticle further comprises poly(histidine)-polyethylene glycol (PH-PEG) or lipid poly histidine. Copending claim 8 teaches
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. The nanoparticle can be further associated with an antigen, such an antigen derived from cdk4 (copending claim 14). The nanoparticle can be further associated with an adjuvant such as CPG (copending claim 18). Although the copending claims do not specify the composition comprises crystalline polymorphic forms of the STING agonists, according to the instant specification, the polymorphic forms are formed by merely mixing STING agonists with metal ions at room temperature and adding PEG-polyhistidine in a one-pot synthesis (pg. 68, lines 29-34), which is comparable to method disclosed in the copending application (pg. 102, lines 14-20). Furthermore the instant specification describes that mixing STING agonists with Zn2+ and/or Mn2+ crystalline polymorphic forms (e. g., coordinated polymeric forms) capable of assembling into homogeneous and stable nanoparticles in the presence of poly-histidine33-polyethylene glycol (pg. 3, lines 1-4). Figure 11A on page 11 of the drawings demonstrates this one-pot synthesis results in nanoparticles containing the coordinated polymorphs within (drawings, pg. 11, figure 1A). Although the copending claims do not use the phrase crystalline directly, however, recites “coordination” throughout the specification, as in the phrase “polymer stabilized metal-CDN coordination nanoparticles” or “CDN-metal ion coordination polymers” (pg. 28, lines 9-16, pg. 101, line 29). Wherein the instant specification states that coordinated polymeric forms are an example of crystalline polymorphic forms, and the copending specification describes “CDN-metal ion coordination polymers”, absent evidence to the contrary, the compositions of the instant claims directed to crystalline polymorphs comprising STING agonists and one or more metal ions associated with polyhistidine-PEG and the copending claims directed to a composition comprising STING agonists and one or more cations further comprising polyhistidine-PEG both necessarily resulted in crystalline polymorphic forms of STING agonists with metal ions and consequently form nanoparticles in the presence of PEG-polyhistidine.
Regarding claims 2, 5-6: As discussed above, the copending claims teach wherein the composition comprises poly(histidine)-polyethylene glycol (PH-PEG). They do not specify the amount of repeating units of PEG units or polyhistidine33 wherein the length can vary between 1-500 units and 1-50 units respectively. They further do not teach the concentration of ingredients in the composition or STING agonist to metal ratio. However, wherein the general ingredients are disclosed in the copending application, optimization of concentrations would be within the technical grasp of the skilled artisan given the broad range of concentrations/ratio claimed, absent evidence of a demonstration of the criticality of the claimed range (See MPEP 2144.05 (II)). Additionally, wherein the copending claims teach poly(histidine)-polyethylene glycol (PH-PEG) generally, the instant claims are encompassed which include PEG polyhistidine units starting at 1 unit. The copending specification demonstrates the use of H33-PEG specifically, which would direct a person of ordinary skill to this reagent specifically (pg. 105, lines 30-33).
Claims 12-13, 17-18, 24-25, 27, 41 and 46-48 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Application 17/259819 (US 2022/0072023, cited on PTO-892, Notice of Allowance mailed December 18, 2025) as applied to claims 1-2, 5-7, 11, 46, and 48 above in view of Charnley (WO 2017/175156, IDS filed November 4, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 12, 17, 24-25, 27, 41, and 46-48: As discussed above, the copending claims teach compositions comprising STING agonists, cations and poly(histidine)-polyethylene glycol (PH-PEG) which would necessarily form crystal polymorphs. The nanoparticle can be further associated with an antigen, such an antigen derived from cdk4 (copending claim 14). The nanoparticle can be further associated with an adjuvant such as CPG (copending claim 18).
The copending claims do not teach wherein the composition comprising STING agonists are used for the treatment of cancer, such as skin cancer or to a human subject. The copending claims do not teach wherein the composition is used as an analgesic for pain. The copending claims do not teach wherein the composition is formulated as a skin patch.
However, Charnley teaches compounds of formula (I) which are STING modulators (pg. 9, lines 18-25) and STING agonists are useful for the treatment of skin cancers via patch delivery (pg. 4, lines 20-23). Charnley teaches the compounds may be administered via subcutaneous injection. Charnley teaches STING agonists of the invention can be combined with an analgesic, as an analgesic composition for the treatment of ALS (pg. 72, lines 5-10).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to apply the composition for the treatment of skin cancer in a human subject by way of skin patch, formulate as a subcutaneous injection, or include the composition in an analgesic composition for ALS. A person of ordinary skill would have had a reasonable expectation of success as these are established known applications of STING agonists within the art of treating diseases.
Regarding claim 13: The copending claims do not teach wherein the administration results in an innate cytokine response mediated through cytokines in the subject, wherein the innate cytokine response is mediated through type 1 interferon. However, Charnley teaches that activation of STING results in induction of type 1 interferons (pg. 4, lines 3-6), thus, wherein the method of administering to patients is rendered obvious, this result naturally flows from practicing the method, thus claim 13 is also rendered obvious.
Regarding claim 18: The copending claims do not specifically teach wherein the composition is administered with an antibody, such as an anti-PD-L1 antibody. However, Charnley teaches other therapeutic agents, such as anti-PD-L1 antibodies can be co-administered with a compound of the invention (pg. 59, lines 23-35). Thus, it would have been prima facie obvious to modify the copending claims such that the composition is administered alongside an anti-PD-L1 antibody. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that this is a known technique in the art for treating diseases such as cancer in cancer immunotherapies.
Claim 31 is rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent Application 17/259819 (US 20220072023, cited on PTO-892, Notice of Allowance mailed December 18, 2025) and Charnley (WO 2017/175156, IDS filed November 4, 2024) as applied to claims 1-2, 5-7, 11-13, 17-18, 24-25, 27, 41, and 46-48 above in view of Wu (BioRxiv, 2020, cited on PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 31: As discussed above, the copending claims in view of the prior art render obvious the method of claim 12. Charnley further teaches the STING modulators of the invention can be useful for infectious disease, such as SARS coronavirus (pgs. 47-48, bridging para.).
The copending claims do not teach wherein the subject is suffering from or at risk of suffering from conditions and symptoms caused by a SARS-CoV-2 related viral infection, and wherein the administration results in reduced proinflammatory cytokine release by immune effector cells.
However, Wu teaches that STING agonists may be useful as an adjuvant for SARS-CoV-2 vaccine (i.e. subjects at risk, abstract). Wherein STING agonists are recognized for this ability to act as adjuvants, it is prima facie obvious to substitute equivalents known for the same purpose (See MPEP 2144.06 (II)).
Taken together, it would have been prima facie obvious to modify the copending claims such that the composition is administered as an adjuvant to a subject at risk of suffering from a SARS-CoV-2 related infection. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success given that this is a known technique in the art for STING agonists as vaccine adjuvants, and it is prima facie obvious to substitute one STING agonist composition for another. Although the prior art does not teach wherein the composition results in reduced proinflammatory cytokine release by immune effector cells, wherein it would be obvious to apply the method to SARS-CoV-2 related infection, this property necessarily flows as a result of practicing the method.
Conclusion
No claims are allowed in this action.
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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693