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 .
Priority
The instant application is a 35 U.S.C. 371 national phase application and claims priority to International Application No. PCT/EP2022/057007 (filing date 03/17/2022), which claims the benefit of the prior-filed European Provisional Patent Application Nos. EP21217382.7 (filing date 12/23/2021) and EP21163292.2 (filing date 03/17/2021).
Status of Application/Claims
The preliminary amendment, filed 03/13/2024, is acknowledged. Claim 13 is canceled. Claims 1-12 are currently amended. Claims 1-12 are currently pending and are examined on the merits herein.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on 01/02/2024, 10/08/2025, and 02/04/2026 have been fully considered by the examiner.
Specification
The use of the terms Cremophor, Sigma/Sigma-Aldrich, Santa Cruz Technology, Cytiva, BIAcore, OriGene, , R&D Systems/R&D, Euroclone, BioLegend, Allianc, Applied Biosystems, and Selleckchem, which are trade names or marks used in commerce, have been noted in this application. The terms should be in all caps wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 3, 7, and 9 are objected to because of the following informalities:
Claim 3 recites, “…and the inhibitor…” in line 3, which should be corrected to “…and the C5aR1 inhibitor…”.
Claim 7 recites, “…is for the acute treatment…” in line 2, which should be corrected to “…is for acute treatment…”; and, “…and the inhibitor…” in line 3, which should be corrected to “…and the C5aR1 inhibitor…”.
Claim 9 recites, “…is a C5aR1 antagonist…” in line 2, which should be corrected to “…is a C5aR1 competitive antagonist…”.
Appropriate correction is required.
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 2, 9, and 12 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.
Claims 2 and 9 contain the trademarks/trade names NabTM (claim 2, line 2) and Vynpenta® (claim , line 4). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name NabTM is used to identify/describe a taxane; and, Vynpenta® is used to identify/describe a C5aR1 antagonist. Accordingly, the identification/description is indefinite.
Claim 12 recites the limitation "said compound" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112(a)
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 and 3 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 the treatment or improvement of taxane-induced HSR, do not reasonably provide enablement for prevention of taxane-induced. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue,’ not ‘experimentation.’” (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: the nature of the invention; the breadth of the claims; the amount of direction provided by the inventor; The existence of working examples; the state of the prior art; the level of predictability in the art; the quantity of experimentation needed to make or use the invention based on the content of the disclosure and the level of one of ordinary skill. While all of these factors are considered, a sufficient amount for amount for a prima facie case are discussed below.
The nature of the invention
Claims 1 and 3 are drawn to the prevention of taxane-induced HSR.
The breadth of the claims
The claims are broad and inclusive of a large group of taxanes and individuals.
The instant specification defines the term "prevention" as “…to obtain partial or complete prevention of a disorder or pathological event before this is established or occurs” (p.6, para.4).
The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. The onset of HSR is unpredictable and can involve more than one mechanism.
The amount or direction provided by the inventor/ the existence of working examples
The examples of the instant disclosure studied the treatment of taxane-induced HSR.
Example 6 of applicant disclosure describes assessment of C5aR1 inhibitor DF3966A treatment of mouse and human macrophages after paclitaxel exposure (p.24; Figures 13 and 15-16); Example 8 describes effective treatment of paclitaxel-induced HSR in mice with DF3966A C5aR1 inhibitor (p.25-26).
The examples provided do not demonstrate the prevention of onset of paclitaxel-induced HSR or any other taxane-induced prevention of HSR. Additionally, the disclosure does not discuss, or demonstrate through working examples, a method that could be used to determine that taxane-induced HSR was prevented using the claimed agents as there is no disclosed method to determine that taxane-induced HSR would have predictably occurred without treatment.
The state of the prior art/ the level of predictability in the art
There are no art recognized methods that could be used to establish that taxane-induced HSR was prevented using the claimed therapeutic products or methods. Additionally, there are no art recognized methods that could be used to identify subjects who would have predictably developed taxane-induced HSR, without undue experimentation, in order to determine that HSR was prevented using the claimed methods.
Demoly, et al. International consensus on drug allergy. Allergy (2014), 69, p.420-437 (herein referred to as Demoly) teaches that drug reactions resembling allergy are called drug hypersensitivity reactions (DHRs), which may be allergic or nonallergic in nature, with drug allergies being immunologically mediated (p.420, abstract). Demoly teaches that DHRs are the adverse effects of pharmaceutical formulations (including active drugs and excipients) that clinically resemble allergy (p.421, col.2, para.2). Thus, the HSR can be due to the excipient or the drug itself. Demoly teaches that corticosteroids and H1-antihistamines are useful for nonallergic DHRs, including some chemotherapy drugs, but that corticosteroids and H1-antihistamines may not reliably prevent IgE-dependent anaphylaxis (p.432, col.1, para.1).
Picard, et al. Risk stratification and skin testing to guide re-exposure in taxane-induced hypersensitivity reactions. J. Allergy Clin. Immunol. (2016), 137:7, p.1154-1164 and 1164.e1-e12 (herein referred to as Picard) teaches that the optimal approach to patients with HSRs to taxanes has not been established (abstract). Further, Picard teaches risk stratification and skin testing to guide re-exposure in taxane-induced HSR, but explains that, “Depending on the initial risk stratification and tolerance to re-exposure, patients were then treated with shorter desensitization protocols, challenge, or both with the aim of resuming regular infusions, except in patients with a severe immediate initial HSR” (abstract). Picard teaches that HSR can be immediate or delayed (Fig.1). Thus, the prior art suggests that the response to taxanes, and severity thereof, in patients exposed to taxanes is not predictable.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Studies regarding detection and prevention of taxane-induced HSR are underway that aim to improve earlier detection and better treatments for these diseases. However, based on the disclosure and combination of teachings by the prior art, while there are methods for treatment of taxane-induced HSR, there is no known or disclosed method through which an ordinarily skilled artisan would have been able to predictably identify subjects who would have predictably developed taxane-induced HSR in order to determine that HSR was prevented using the claimed methods. Therefore, in order to practice the invention as claimed, an ordinarily skilled artisan would have to participate in undue experimentation to determine a method that would allow for the prevention taxane-induced HSR.
In view of the Wands factors discussed above, a person of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the claimed invention. As such, instant claims 1 and 3 were determined to not meet the scope of enablement requirement of 35 U.S.C. 112(a).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 7-8, and 11-12 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO2019115493A2—Brandolini, et al. (publication date:06/20/2019; effective filing date 12/12/2017; herein referred to as Brandolini).
Brandolini teaches C5aR inhibitors, including noncompetitive allosteric inhibitors against C5aRs for a method of treatment and/or prevention of chemotherapy-induced iatrogenic pain (CIIP; title; abstract; ). Brandolini teaches that chemotherapeutic agents most commonly associated with onset of pain include taxanes, and specifically names paclitaxel, cabazitaxel, and docetaxel (p.3, para.2). Brandolini teaches that the absence of C5a/C5aR determines less development of iatrogenic pain (i.e., the mechanism involves the ligand/receptor interaction); and that there is less mechanical and heat hypersensitivity in C5aR-/- mice during both induction and maintenance of CIIP (p.30, para.3). Brandolini teaches methods of treatment, including acute treatment with DF3966A and DF3966Y inhibitors, on mechanical, cold, and heat sensitivity in response to paclitaxel (p.24-26). Brandolini teaches assessments wherein the C5aR inhibitor was administered 1 hour prior to paclitaxel and on days 1, 3, 5, and 7 (i.e., one or more times; i.e., between 30m and 24 hours prior to taxane administration). Brandolini also specifically teaches non-competitive allosteric C5aR inhibitors of instant claim 11 of compounds having general formula (I) (i.e., instant claim 1—page 3,line 2 through page 5, lines 1-14 and lines 20-32 and through lines 1-14; Brandolini p.11-15); and, teaches 24 of the 27 inhibitors listed in instant claim 12. (i.e., instant claim 12—page 6, lines 4-20 through page 7, lines 1-4 and 7-8; p.19, para.2; p.32, Example 3; p.33, Examples 5-6; Brandolini p.18-19).
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.
Claims 1, 3, and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019115493A2—Brandolini, et al. (publication date:06/20/2019; effective filing date 12/12/2017; herein referred to as Brandolini); and, further in view of Picard, et al. Risk stratification and skin testing to guide re-exposure in taxane-induced hypersensitivity reactions. J. Allergy Clin. Immunol. (2016), 137:7, p.1154-1164 and 1164.e1-e12 (herein referred to as Picard).
Brandolini teaches methods of C5aR1 inhibitor treatment for taxane hypersensitivity wherein the inhibitor is administered one or more times prior to each administration of taxane, as described above for instant claims 1 and 3.
Brandolini does not teach that the individual is a cancer patient that has had a previous hypersensitivity reaction episode to a taxane, has resulted positive in a skin prick test for sensitivity to said taxane and/or has a history of atopy (instant claim 5); or, that the inhibitor is administered in combination with one or more corticosteroids and/or antihistamines (instant claim 6).
Picard teaches safety and efficacy of risk based on severity of initial hypersensitivity reactions (HSRs) and skin testing for guiding taxane reintroduction in patients with HSR to these agents (title; abstract). Picard teaches that antineoplastics are the third leading cause of fatal drug-induced anaphylaxis in the United States, and taxanes are among the most frequently implicated; and that HSR is used to designate adverse reactions with features suggestive of mast cell/basophil degranulation that occur during taxane infusions (p.1164, col.2, para.1). Picard adds that taxanes are an integral part of the chemotherapeutic regimen used in gynecologic malignancies and are frequently administered in patients with various cancers, including breast, prostate, and lung cancers. Picard teaches that in early clinical trials paclitaxel and docetaxel caused a high rate of immediate HSRs; and, that premedication with antihistamines and corticosteroids for paclitaxel and with corticosteroids alone for docetaxel successfully reduced the risk of immediate HSRs to 10% or less, but that severe immediate HSRs still occur in around 1% of patients (p.1154, col.2, para.2). Picard teaches that HSRs are generally attributed to surfactants used in taxane formulations, which can cause complement activation, resulting in anaphylatoxin formation; and, that some patients react to the taxane moiety rather than the surfactants. Further, Picard teaches that IgE-mediated HSR to paclitaxel has been shown to be demonstrated by a positive immunoblot assay and skin test result (p.1154, col1., para.3). Picard also teaches that atopy was associated with an increased risk of an immediate HSR during desensitization or challenge (p1159, col.2, para.2; p.1162, col.2, para.2; Tables 4 and 5).
Regarding instant claim 5, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Brandolini and Picard by using a method of C5aR1 inhibitor treatment of hypersensitivity to taxanes (taught by Brandolini) for cancer patients that have had previous HSR episode(s), have had a positive skin prick test or have a history of atopy (taught by Picard), in order to arrive at the instantly claimed invention because the combination of prior art teachings suggests that these patients would benefit from an HSR treatment. One of ordinary skill in the art would have a reasonable expectation of success because Picard teaches patient populations for taxane patients that have had previous HSRs, positive skin tests, and atropy and Brandolini teaches the involvement of the C5a/C5aR interaction in HSR and the benefit of treating taxane-induced HSR with C5aR1 non-competitive allosteric inhibitors to reduce mechanical allodynia and temperature-sensitive symptoms of HSR.
Regarding instant claim 6, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of Brandolini and Picard by further administering one or more corticosteroids and/or antihistamines (taught by Picard) in combination with the C5aR1 inhibitor treatment of hypersensitivity to taxanes (taught by Brandolini), in order to arrive at the instantly claimed invention, in order to receive the predictable benefit that corticosteroid/antihistamine treatment for paclitaxel and corticosteroid treatment for docetaxel would reduce the risk of immediate HSR (taught by Picard). One of ordinary skill in the art would have a reasonable expectation of success because Picard teaches desensitization treatment following taxane exposure involving corticosteroids and H1-blockers (i.e., antihistamine; p.1164.e1, col.1, para.1).
Claims 1 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Brandolini, as applied to claim 1 above; and, further in view of US20190183976A1—Seen, et al. (publication date: 06/20/2019; effective filing date: 12/19/2017; herein referred to as Seen).
Brandolini teaches methods of C5aR1 inhibitor treatment for taxane hypersensitivity, as described above for instant claim 1.
Brandolini does not teach that the inhibitor is a C5aR1 competitive antagonist selected from the group consisting of the competitive antagonist (instant claim 8) inhibitors listed in instant claim 9.
Seen teaches treatment of cancer using GPCR inhibitors, including C5aR1 inhibitors avacopan, PMX53, PMX205, W54011, and DF2593A (i.e., antagonists; abstract; p.10, [0145]; Table 3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Brandolini and Seen by using avacopan, PMX53, PMX205, or W54011 as the C5aR1 antagonist inhibitor (taught by Seen) in the method of treating taxane-induced HSR using a C5aR1 inhibitor (taught by Brandolini), in order to arrive at the instantly claimed invention, because the combination of prior art elements suggests that taxane-exposed patients benefit from C5aR1 inhibition which would alleviate HSR symptoms. One of ordinary skill in the art would have a reasonable expectation of success because Brandolini teaches that cancer patients who receive chemotherapy with taxanes can develop HSR symptoms such as CIIP.
Claims 1, 8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Brandolini, as applied to claim 1 above; and, further in view of US20100129346A1—Mackay (publication date: 05/27/2010; effective filing date: 08/22/2006; herein referred to as Mackay).
Brandolini teaches methods of C5aR1 inhibitor treatment for taxane hypersensitivity, as described above for instant claim 1.
Brandolini does not teach that the inhibitor is a anti-C5aR1 antibody selected from the group consisting of the anti-C5aR1 antibodies (instant claim 8) listed in instant claim 10.
Mackay teaches anti-C5aR antibodies for therapeutic methods (title; abstract). Mackay teaches that proteolysis of complement proteins C3-C5 gives rise to aminoterminal cationic fragments with signaling molecules called anaphylatoxins; and that C5a is the most potent and elicits the broadest responses as the “complete” pro-inflammatory mediator that can elicit chemotaxis of all myeloid lineages at sub-nanomolar levels (p.1, [0003]). Mackay teaches that diseases or conditions of humans or other specifies that can be treated with anti-C5aR antibodies include inflammatory or allergic diseases and conditions, including respiratory allergic diseases including hypersensitivity lung diseases, as well as anaphylaxis or HSRs, drug allergies, and granulomatous disease (p.13, [0206]). Mackay teaches that the activities of C5a are mediated by the binding of the C5a to its receptor (C5aR; p.1, [0004]). Mackay teaches that inhibition of the C5a responses with C5aR antagonists should reduce the acute inflammatory response mediated via C5a (p.1, [0006]); and, that anti-C5aR antibodies of their disclosure can block the binding of one or more ligands to the receptor thereby blocking the downstream cascade leading to the above disorders (p.13, [0207]). Mackay further specifically teaches that monoclonal antibodies 3C5 and 7F3 showed strong binding to receptor epitopes (p.19, [0292]; Table 2).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Brandolini and Mackay by using an anti-C5aR inhibitor that is the 3C5 mAb or 7F3 mAb (taught by Mackay) in the method of treating taxane-induced HSR using a C5aR1 inhibitor (taught by Brandolini), in order to arrive at the instantly claimed invention, because the combination of prior art elements suggests that taxane-exposed patients benefit from C5aR1 inhibition which would alleviate HSR symptoms. One of ordinary skill in the art would have a reasonable expectation of success because Brandolini teaches that cancer patients who receive chemotherapy with taxanes can develop HSR symptoms such as CIIP; and, Mackay and Brandolini teach that C5aRs are activated by the C5a ligand. One of ordinary skill in the art would be further motivated to use the 3C5 or 7F3 mAb because Mackay teaches that these antibodies exhibit strong binding at 0.48 mM and 0.7 nM binding affinities, respectively.
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 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 8, and 20-21 of copending Application No. 18/799,076 (herein referred to as App’076); in view of Brandolini; in further view of Picard; in further view of Seen; and, further in view of Mackay.
App’076 teaches a method of preventing and/or treating chemotherapy-induced iatrogenic pain (CIIP) by administering a C5aR inhibitor to a subject, and wherein the CIIP is due to taxanes, and specifically paclitaxel (App’076 claims 1, 12, 20-21; instant claims 1-2). App’076 teaches that the C5aR inhibitor is selected from (R)-arlyalkylamino derivative or a pharmaceutically acceptable salt thereof and an (R)-4-(heteroaryl)phenylethyl compound or pharmaceutically acceptable salt thereof; and, wherein the former is the compound described by the formula (I) limitations of App’076 claim 4-5/instant claim 11 and wherein the inhibitor is selected from any of the compounds listed in App’076 claim 8, which are all instantly claimed and recited in instant claim 12 (App’076 claims 3-5, and 8; instant claims 8, 11-12).
App’076 does not teach that the inhibitor is administered one or more times prior to each administration of taxane (instant claim 3); that the inhibitor is administered one or more times between 30 minutes and 24 hours before administering the taxane (instant claim 4); that the individual is a cancer patient that has had a previous hypersensitivity reaction episode to a taxane, has resulted positive in a skin prick test for sensitivity to said taxane and/or has a history of atopy (instant claim 5); that the inhibitor is administered in combination with one or more corticosteroids and/or antihistamines (instant claim 6); that the treatment is for acute treatment of HSR to taxane (instant claim 7); that the inhibitor is a C5aR1 competitive antagonist selected from the group consisting of the competitive antagonist (instant claim 8) inhibitors listed in instant claim 9; or, that the inhibitor is an anti-C5aR1 antibody selected from the group consisting of the anti-C5aR1 antibodies (instant claim 8) listed in instant claim 10.
Brandolini teaches C5aR inhibitors, including noncompetitive allosteric inhibitors against C5aRs for a method of treatment and/or prevention of chemotherapy-induced iatrogenic pain (CIIP; title; abstract; ). Brandolini teaches that chemotherapeutic agents most commonly associated with onset of pain include taxanes, and specifically names paclitaxel, cabazitaxel, and docetaxel (p.3, para.2). Brandolini teaches that the absence of C5a/C5aR determines less development of iatrogenic pain (i.e., the mechanism involves the ligand/receptor interaction); and that there is less mechanical and heat hypersensitivity in C5aR-/- mice during both induction and maintenance of CIIP (p.30, para.3). Brandolini teaches methods of treatment, including acute treatment with DF3966A and DF3966Y inhibitors, on mechanical, cold, and heat sensitivity in response to paclitaxel (p.24-26). Brandolini teaches assessments wherein the C5aR inhibitor was administered 1 hour prior to paclitaxel and on days 1, 3, 5, and 7 (i.e., one or more times; i.e., between 30m and 24 hours prior to taxane administration). Brandolini also specifically teaches non-competitive allosteric C5aR inhibitors of instant claim 11 of compounds having general formula (I) (i.e., instant claim 1—page 3,line 2 through page 5, lines 1-14 and lines 20-32 and through lines 1-14; Brandolini p.11-15); and, teaches 24 of the 27 inhibitors listed in instant claim 12. (i.e., instant claim 12—page 6, lines 4-20 through page 7, lines 1-4 and 7-8; p.19, para.2; p.32, Example 3; p.33, Examples 5-6; Brandolini p.18-19).
Regarding claims 3-4 and 7-8, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’067 and Brandolini by using a C5aR1 non-competitive allosteric inhibitor for the acute treatment of HSR due to a taxane that is paclitaxel (taught by App’076 and Brandolini), docetaxel (taught by Brandolini), or cabazitaxel (taught by Brandolini) by administering the inhibitor one or more times between 30 minutes and 24 hours prior to each taxane administration (taught by Brandolini), in order to arrive at the instantly claimed invention, because the combination of prior art elements suggests that cancer patients exhibiting HSR/CIIP as a result of taxane chemotherapy benefit from treatment with the C5aR1 inhibitor (taught by Brandolini and App’076). One of ordinary skill in the art would have a reasonable expectation of success because Brandolini teaches effective timing of administration of the inhibitor prior to acute taxane treatment to reduce HSR.
Picard teaches safety and efficacy of risk based on severity of initial hypersensitivity reactions (HSRs) and skin testing for guiding taxane reintroduction in patients with HSR to these agents (title; abstract). Picard teaches that antineoplastics are the third leading cause of fatal drug-induced anaphylaxis in the United States, and taxanes are among the most frequently implicated; and that HSR is used to designate adverse reactions with features suggestive of mast cell/basophil degranulation that occur during taxane infusions (p.1164, col.2, para.1). Picard adds that taxanes are an integral part of the chemotherapeutic regimen used in gynecologic malignancies and are frequently administered in patients with various cancers, including breast, prostate, and lung cancers. Picard teaches that in early clinical trials paclitaxel and docetaxel caused a high rate of immediate HSRs; and, that premedication with antihistamines and corticosteroids for paclitaxel and with corticosteroids alone for docetaxel successfully reduced the risk of immediate HSRs to 10% or less, but that severe immediate HSRs still occur in around 1% of patients (p.1154, col.2, para.2). Picard teaches that HSRs are generally attributed to surfactants used in taxane formulations, which can cause complement activation, resulting in anaphylatoxin formation; and, that some patients react to the taxane moiety rather than the surfactants. Further, Picard teaches that IgE-mediated HSR to paclitaxel has been shown to be demonstrated by a positive immunoblot assay and skin test result (p.1154, col1., para.3). Picard also teaches that atopy was associated with an increased risk of an immediate HSR during desensitization or challenge (p1159, col.2, para.2; p.1162, col.2, para.2; Tables 4 and 5).
Regarding instant claim 5, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’076 and Picard by using a method of C5aR1 inhibitor treatment of hypersensitivity to taxanes (taught by App’076) for cancer patients that have had previous HSR episode(s), have had a positive skin prick test or have a history of atopy (taught by Picard), in order to arrive at the instantly claimed invention because the combination of prior art teachings suggests that these patients would benefit from an HSR treatment. One of ordinary skill in the art would have a reasonable expectation of success because Picard teaches patient populations for taxane patients that have had previous HSRs, positive skin tests, and atropy and App’076 teaches the involvement of the C5a/C5aR interaction in HSR and the benefit of treating taxane-induced HSR with C5aR1 non-competitive allosteric inhibitors to reduce mechanical allodynia and temperature-sensitive symptoms of HSR.
Regarding instant claim 6, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the teachings of App’076 and Picard by further administering one or more corticosteroids and/or antihistamines (taught by Picard) in combination with the C5aR1 inhibitor treatment of hypersensitivity to taxanes (taught by App’076), in order to arrive at the instantly claimed invention, in order to receive the predictable benefit that corticosteroid/antihistamine treatment for paclitaxel and corticosteroid treatment for docetaxel would reduce the risk of immediate HSR (taught by Picard). One of ordinary skill in the art would have a reasonable expectation of success because Picard teaches desensitization treatment following taxane exposure involving corticosteroids and H1-blockers (i.e., antihistamine; p.1164.e1, col.1, para.1).
Seen teaches treatment of cancer using GPCR inhibitors, including C5aR1 inhibitors avacopan, PMX53, PMX205, W54011, and DF2593A (i.e., antagonists; abstract; p.10, [0145]; Table 3).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’076 and Seen by using avacopan, PMX53, PMX205, or W54011 as the C5aR1 antagonist inhibitor (taught by Seen) in the method of treating taxane-induced HSR using a C5aR1 inhibitor (taught by App’076), in order to arrive at the instantly claimed invention, because the combination of prior art elements suggests that taxane-exposed patients benefit from C5aR1 inhibition which would alleviate HSR symptoms. One of ordinary skill in the art would have a reasonable expectation of success because App’076 teaches that cancer patients who receive chemotherapy with taxanes can develop HSR symptoms such as CIIP.
Mackay teaches anti-C5aR antibodies for therapeutic methods (title; abstract). Mackay teaches that proteolysis of complement proteins C3-C5 gives rise to aminoterminal cationic fragments with signaling molecules called anaphylatoxins; and that C5a is the most potent and elicits the broadest responses as the “complete” pro-inflammatory mediator that can elicit chemotaxis of all myeloid lineages at sub-nanomolar levels (p.1, [0003]). Mackay teaches that diseases or conditions of humans or other specifies that can be treated with anti-C5aR antibodies include inflammatory or allergic diseases and conditions, including respiratory allergic diseases including hypersensitivity lung diseases, as well as anaphylaxis or HSRs, drug allergies, and granulomatous disease (p.13, [0206]). Mackay teaches that the activities of C5a are mediated by the binding of the C5a to its receptor (C5aR; p.1, [0004]). Mackay teaches that inhibition of the C5a responses with C5aR antagonists should reduce the acute inflammatory response mediated via C5a (p.1, [0006]); and, that anti-C5aR antibodies of their disclosure can block the binding of one or more ligands to the receptor thereby blocking the downstream cascade leading to the above disorders (p.13, [0207]). Mackay further specifically teaches that monoclonal antibodies 3C5 and 7F3 showed strong binding to receptor epitopes (p.19, [0292]; Table 2).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of App’076 and Mackay by using an anti-C5aR inhibitor that is the 3C5 mAb or 7F3 mAb (taught by Mackay) in the method of treating taxane-induced HSR using a C5aR1 inhibitor (taught by App’076), in order to arrive at the instantly claimed invention, because the combination of prior art elements suggests that taxane-exposed patients benefit from C5aR1 inhibition which would alleviate HSR symptoms. One of ordinary skill in the art would have a reasonable expectation of success because App’076 teaches that cancer patients who receive chemotherapy with taxanes can develop HSR symptoms such as CIIP; and, Mackay and Brandolini teach that C5aRs are activated by the C5a ligand. One of ordinary skill in the art would be further motivated to use the 3C5 or 7F3 mAb because Mackay teaches that these antibodies exhibit strong binding at 0.48 mM and 0.7 nM binding affinities, respectively.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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