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 .
Information Disclosure Statement
The information disclosure statement (IDS) filed 10/17/2024, was in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS documents were considered. A signed copy of Form PTO-1449 is enclosed herewith.
Status of the Claims
Claims 1-14 are pending.
Priority
This application, filed on 10/17/2024, is a DIV of U.S. Application No. 15/743,721, filed on 01/11/2018 (U.S. Patent No. 12,150,933), which is a is a 371 of PCT/EP2016/066511, filed on 07/12/2016, which claims priority to EPO Application No. 15176726.6, filed on 07/14/2015. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112
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 1-14 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 2-14 depend from claim 1 and are therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for reasons set forth below.
Claim 1 recites the limitation of “an effective amount”, however, a person of the ordinary skill in the art cannot reasonably determine the meets and bounds of the recited limitation in the claims. The specification (see, e.g., page 15, lines 7-12), states:
“As used herein, a "therapeutically effective amount" refers to an amount sufficient to achieve treatment or prevention of the disease. Determination of the effective amounts is well within the capability of those skilled in the art based upon the achievement of a desired effect. An effective amount will depend on factors including, but not limited to, the weight of a subject and/or the degree to which the disease or unwanted condition from which a subject suffers.” Emphasis added.
The phrase “an effective amount” has been held to be indefinite when the claim fails to state the function which is to be achieved and more than one effect can be implied from the specification or the relevant art. Please see MPEP § 2173.05(c)(III).
In the instant case, the more than one effect that can implied from the specification are: i) treating IC/PBS; ii) treating OAB; iii) preventing IC/PBS; and iv) preventing OAB. The specification does not appear to provide guidelines that are elaborate enough for determining “an effective amount” for a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of formula (II), recited in claim 1, which would: i) treat IC/PBS; ii) treat OAB; iii) prevent IC/PBS; and iv) prevent OAB. A person skilled in the art cannot tell from the specification, what is “an effective amount”, for a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of formula (II), recited in claim 1.
The term “an effective amount” is a relative set of measure in that it is not defined by the claim or the specification to any specific dosage or dosage range, for a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of formula (II). The specification does not provide a standard for ascertaining the requisite degree. Thus, a person skilled in the art would not be able to draw a clear boundary between what is and is not covered by the claim.
A patent must be precise enough to afford clear notice of what is claimed, thereby "'appris[ing] the public of what is still open to them.'" Markman v. Westview Instruments, Inc., 517 U.S. 370, 373 (quoting McClain v. Ortmayer, 141 U.S. 419, 424 (1891)). Otherwise, there would be "[a] zone of uncertainty which enterprise and experimentation may enter only at the risk of infringement claims." United Carbon Co. v. Binney & Smith Co., 317 U.S. 228, 236 (1942). A claim fails to satisfy this statutory requirement and is thus invalid for indefiniteness if its language, when read in light of the specification and the prosecution history, "fail[s] to inform, with reasonable certainty, those skilled in the art about the scope of the invention." Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120, 2124 (2014).
This lack of clarity makes it impossible to ascertain with reasonable precision when that claim is infringed and when it is not. Lacking such clarity, the skilled artisan would not be reasonably apprised of the metes and bounds of the subject matter for which Applicants seek patent protection. Rather, a subjective interpretation of the claimed language would be required. However, as such is deemed inconsistent with the tenor and express language of 35 U.S.C. § 112, second paragraph, the claims are deemed properly rejected. Appropriate correction is required.
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 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Piemonti et al (hereinafter “Piemonti”, WO2011042465A1, published 04/14/2011), as evidenced by Moriconi et al (hereinafter “Moriconi”, ACS Med. Chem. Lett., 2011, 2, 768-773).
Applicants’ invention (e.g., claim 1), is directed to a method for treating and/or preventing cystitis/painful bladder syndrome (IC/PBS) and/or overactive bladder (OAB), in a subject in need thereof, with an effective amount of a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of formula (II):
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, wherein: i) R’ = H; and ii) R = SO2Ra (Ra = linear or branched C1-4 alkyl or halo C1-3 alkyl) or a pharmaceutically acceptable salt thereof.
The term “an effective amount” is not defined by the claim or the specification to any specific dosage or dosage range, for a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of formula (II). Accordingly, for the purpose of examination, an amount of a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of formula (II), or a pharmaceutically acceptable salt thereof, that is employed in order to generate the desired therapeutic outcome, are included in the interpretation of “an effective amount”.
Regarding claims 1-4, Piemonti (see pages 3-4 and 7-8), teaches a method comprising administering to mice, R(-)-2-[(4'-trifluoromethanesulfonyloxy)phenyl]propionyl-methanesulfonamide (meraxin):
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, a compound of formula (II), wherein: i) R’ = H; and R = SO2CH3. The mice are not disclosed as suffering from IC/PBS and/or OAB. A subject in need of a prevention from IC/PBS and/or OAB, would not be expected to have the IC/PBS and/or OAB.
Moriconi (see abstract and Table 1) discloses meraxin (compound 19) as a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor.
Therefore, claims 1-4 are anticipated by Piemonti as evidenced by Moriconi, to the extent that claims 1-4 read on the prevention of IC/PBS and/or OAB.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Piemonti (WO2011042465A1) as evidenced by Moriconi (ACS Med. Chem. Lett., 2011), as applied to claims 1-4 above and in view of Brito et al (hereinafter “Brito”, Cells, 2014, 3, 517-545).
The limitations of claims 1-4 as well as the corresponding teachings of Piemonti as evidenced by Moriconi, are described above and are hereby incorporated into the instant rejections.
Claims 5-9 depend from claim 4 and claims 10-14 depend from claim 1. Claims 5-14 further require at least one additional pharmaceutically active compound.
Although Piemonti as evidenced by Moriconi is not explicit in disclosing the limitations of claims 5-14, the claimed inventions would have been obvious over Piemonti as evidenced by Moriconi. This is because at the time of the instant invention, the utility of at least one additional pharmaceutically active compound (e.g., TRPV1 antagonist) in the prevention of bladder cystitis, was known in the art. For example, Brito (see e.g., page 526), discloses that bladder cystitis induced by cyclophosphamide (a chemotherapeutic agent) in mice and rats is characterized by mechanical bladder hyperactivity which is antagonized by pretreatment with TRPV1 antagonist SB-366791.
Accordingly, at the time of the instant invention, a person skilled in the art would have envisaged a method for preventing IC/PBS and/or OAB in a subject in need thereof, with an effective amount of a compound of formula (II) (e.g., meraxin) and at least one additional pharmaceutically active compound (e.g., TRPV1 antagonist), in the disclosures of Piemonti as evidenced by Moriconi and Brito.
One skilled in the art would have had a reasonable expectation that a combination of meraxin and a TRPV1 antagonist (e.g., SB-366791), would exhibit enhanced efficacy, when compared to a monotherapy comprising meraxin alone or SB-366791 alone.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Allegretti et al (hereinafter “Allegretti”, WO2005090295A2, published 09/29/2002) as evidenced by Moriconi (ACS Med. Chem. Lett., 2011), in view of: 1) Vera et al (hereinafter “Vera”, Neurology and Urodynamics, 2010, 29, 1451-1457); and 2) Chuang et al (hereinafter “Chuang”, BMC Immunology, 2010, 11(50), 1-8).
Similar to the Applicants’ invention (see discussions above), Allegretti (see, e.g., abstract, pages 1-10 and Tables I-III) teaches 4-(trifluoromethanesulfonyloxyphenyl)propionic acid compounds of formula (I):
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, as inhibitors of the chemotactic activation of neutrophils (PMN leukocytes) induced by the interaction of Interleukin-8 (IL-8) with CXCR1 and CXCR2 membrane receptors. The compounds are used for the prevention and treatment of pathologies deriving from said activation. Specifically, Allegretti (see page 5, line 11) teaches R(-)-2-[(4'-trifluoromethanesulfonyloxy)phenyl]propionyl-methanesulfonamide (meraxin, see discussions above):
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, among the exemplary compounds.
Moriconi (see abstract and Table 1) discloses meraxin (compound 19) as a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor.
Although Allegretti as evidenced by Moriconi is not explicit in disclosing IC/PBS and/or OAB as pathologies deriving from PMN activation, the claimed invention would have been obvious over Allegretti as evidenced by Moriconi. This is because at the time of the instant invention, IC/PBS and/or OAB were known in the art as pathologies deriving from PMN activation. For example:
1) Vera discloses cyclophosphamide (CYP)-induced cystitis in mice (see abstract) wherein, bladders from mice with CYP-induced cystitis have high numbers of PMN, compared to control cystitis free mice and ISO-1 treated mice with CYP-induced cystitis (see, e.g., pages 1442-1454 and Figure 3).
2) Similar to Allegretti and Vera (see discussions above), Chuang discloses ISO-1 as IL-8 inhibitor (see abstract).
Accordingly at the time of the instant invention, one skilled in the art would have envisaged a method for treating and preventing pathologies deriving from chemotactic activation of PMN induced by the interaction of IL-8 with CXCR1 and CXCR2 (e.g., IC/PBS and/or OAB) in a subject in need thereof, with an inhibitor of said activation (e.g., meraxin), in the disclosures of Allegretti, Vera and Chuang. A person skilled in the art would have had a reasonable expectation that the administration of meraxin would, for example, treat IC/PBS and/or OAB in the subject.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Allegretti (WO2005090295A2) as evidenced by Moriconi (ACS Med. Chem. Lett., 2011), in view of: 1) Vera (Neurology and Urodynamics, 2010); and 2) Chuang (BMC Immunology, 2010) as applied to claims 1-4 above and further in view of Takahashi et al (hereinafter “Takahashi”, Bioorg & Med Chem Lett., 2013, 23, 3154-3156).
The limitations of claims 1-4 as well as the corresponding teachings of Allegretti as evidenced by Moriconi, Vera and Chuang are described above and are hereby incorporated into the instant rejections.
Claims 5-9 depend from claim 4 and claims 10-14 depend from claim 1. Claims 5-14 further require at least one additional pharmaceutically active compound.
Although Allegretti as evidenced by Moriconi, Vera and Chuang do not combine to explicitly disclose the limitations of claims 5-14, the claimed inventions would have been obvious over Allegretti as evidenced by Moriconi, Vera and Chuang. This is because at the time of the instant invention, the utility of at least one additional pharmaceutically active compound (e.g., TRPV1 antagonist) as a therapeutic option for bladder cystitis, was known in the art. For example, Takahashi (see e.g., abstract, Figures 4-5, citation No. 7 and discussions therein), discloses TRPV1 antagonism as a therapeutic option for treating overactive bladder in a rat model of cyclophosphamide (CYP)-induced cystitis.
Accordingly, at the time of the instant invention, a person skilled in the art would have envisaged a method for treating and preventing IC/PBS and/or OAB in a subject in need thereof, with an effective amount of a compound of formula (II) (e.g., meraxin) and at least one additional pharmaceutically active compound (e.g., TRPV1 antagonist), in the disclosures of Allegretti as evidenced by Moriconi, Vera, Chuang and Takahashi.
One skilled in the art would have had a reasonable expectation that a combination of meraxin and a TRPV1 antagonist, would exhibit enhanced efficacy, when compared to a monotherapy comprising meraxin alone or TRPV1 antagonist alone.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Nonstatutory 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 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-17 of U.S. Patent No. 12,150,933 (‘933 patent).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application and the ‘933 patent are similarly drawn to a method for using a CXCR1 inhibitor or a dual CXCR1 and CXCR2 inhibitor. For example, the claims of the instant application (e.g., instant claim 1), are drawn to a method for treating and/or preventing IC/PBS and/or OAB, in a subject in need thereof, with an effective amount of a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of formula (II):
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, whereas, the claims of the ‘933 patent (e.g., claim 10), are directed to a method for preventing IC/PBS and/or OAB, in a subject in need thereof, with an effective amount of a CXCR1 inhibitor or dual CXCR1 and CXCR2 inhibitor compound of the instant claims. Similar to instant claims 5-14, ‘933 patent claims 13-17 further require at least one pharmaceutically active compound.
Therefore, there is sufficient overlap between the claim scopes to render them obvious over each other. Consequently, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the reference application subject matter.
Conclusions
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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