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 .
DETAILED ACTION
Application status
Claims 1-20 are pending in this application.
Priority
It is acknowledged that the instant application is a CON of PCT/US23/12313, filed on 02/03/2023, which claims benefit of 63306530 filed on 02/04/2022.
Election
Applicants' election without traverse of Group I, Claims 1-14 and species (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR in the response filed on 08/21/2026, is acknowledged.
Claims 15-20 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention.
For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/03/2024, 02/09/2026 and 06/09/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 5 is objected to because of the following informalities:
Claim 5 is objected to because the recitation of “antibody anti-CXCL7” can be substantially improved with respect to form. The Examiner suggests replacing the noted phrase with ---anti-CXCL7 antibody---.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.
Claims 1-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon) without significantly more.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of the following steps:
(1) whether the claim is directed to one of the four categories recited in §101 (process, machine, manufacture or composition of matter);
(Revised 2A - Prong 1) do the claims recite an abstract idea (mathematical concepts, mental processes or method of organizing human activity), law of nature or natural phenomenon;
(Revised 2A - Prong 2) do the claims recite additional elements that integrate the judicial exception into a practical application; and
(2B) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. (See 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG))
Question 1: Yes; the claims are directed to a process.
Question 2A – Prong 1: Yes, the claims recite a law of nature / natural phenomenon, namely, the correlation between circulating levels of I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, and a mental process of comparing a measured level to a reference, and ‘identifying’ or ‘determining’.
Question 2A – Prong 2: No, the claims do not recite anything additional which integrate the naturally occurring process into a practical application.
In the instant case, measuring a circulating level of protein by immunoassay is a routine, conventional data-gathering step. It does not integrate the exception into a practical application as it is drawn to simply observing the natural phenomenon. The administration step of claim 1 of an “aneurysm inhibitor” is for treating identified patient population. However, without reciting what the specific “aneurysm inhibitor” is (see below 112(b) rejection), and specific dosage and/or treatment regimen required to treat the identified patient with aneurysm, Applicants have failed to show that the naturally occurring process has been integrated into a practical application.
Question 2B: As noted in answering that of 2A – Prong 2 above, there is nothing in the claims which amounts to significantly more as additional elements of the claimed methods are well-understood be routine and conventional, i.e., immunoassay of cytokines in blood/serum/plasma/CSF; comparing to a reference; giving clopidogrel (a convention drug for anti-platelet therapy), reparixin (a conventional drug used for abdominal aortic aneurysms, which is a CXCR2 inhibitor) to an aneurysm patient, without integrating the naturally occurring process into a practical application. Thus, the claims are drawn to a judicial exception, namely, a naturally occurring process.
Claim Rejections - 35 U.S.C. § 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, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 1, 7, 8 and 11-14 recite the phrase “an aneurysm inhibitor” or “secondary aneurysm inhibitor” (claim 7) which is unclear and indefinite. It is unclear because one of skill in the art cannot determine what the structural boundaries, i.e., metes and bounds of, what is included in ‘aneurysm inhibitors’. The specification fails to define the noted phrases but only exemplifies platelet inhibitors, clopidogrel, anti-CXCL7, and reparixin as being specific examples of an aneurysm inhibitor. Therefore, without a clear definition, the metes and bounds of these functional genus is unclear and indefinite. In the interest of advancing prosecution, the noted phrase is interpreted as “any molecules that are used for the treatment of aneurysm”.
Claims 1 and 8 (claims 2-7 and 9-14 dependent therefrom) recite the phrase “the expression level is … increased relative to a first reference sample” which is unclear and indefinite. It is unclear because the first reference sample is not indicated to be a sample obtained from aneurysm-free populations which would make the ‘reference’ sample to which one of skill in the art can compare to. Just reciting that it is a first reference sample does not define what the metes and bounds of the noted phrase encompasses. In the interest of advancing prosecution, the noted phrase is interpreted as “a first reference sample comprising normal expression levels of I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and uPAR from aneurysm-free populations”.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted step is following stop c): a step of comparing the expression level of the one or more cytokines to a reference sample comprising normal expression levels of the one or more cytokines from aneurysm-free populations. This is essential step for performing the following step d) of claim 8.
Claim 9 (claim 10 dependent therefrom) recites the limitation "the one or more cytokines” in claim 1. There is insufficient antecedent basis for this limitation in the claim. In the interest of advancing prosecution, claim 9 is interpreted to depend from claim 8.
Claim 10 recite the phrase “the expression level is … relative to a second reference sample” which is unclear and indefinite. It is unclear because the second reference sample is not indicated to be a sample obtained from aneurysm-free populations which would make the ‘reference’ sample to which one of skill in the art can compare to. Just reciting that it is a second reference sample does not define what the metes and bounds of the noted phrase encompasses. In the interest of advancing prosecution, the noted phrase is interpreted as “a second reference sample comprising normal expression levels of RANTES, IL-12 p40/p70, MIP-1α, sTNF.RI, MCP-1, MCP-2, MCP-3, MIG, IL-1ra, and IL1-α from aneurysm-free populations”.
The following is a quotation 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.
Claims 1-14 are rejected under 35 U.S.C. § 112(a), written description, 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(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a method of treating an aneurysm in a genus of any subject in need thereof, comprising a) measuring, in a biological sample of the subject, an expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22; b) identifying the subject as having an aneurysm if the expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22 is increased relative to a first reference sample; and c) administering an effective amount of a genus of any aneurysm inhibitors to the genus of any subjects (italicized for added emphasis). See above 112(b) rejection for the claim interpretation.
To satisfy the written description aspect of 35 U.S.C. § 112(a) for a claimed genus of [compositions or methods], it must be clear that: (1) the identifying characteristics of the claimed [compositions or methods] have been disclosed, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these; and (2) a representative number of species within the genus must be disclosed.
University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lily and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description as noted from Enzo Biochemical (see above).
The specification discloses only a few examples of administering clopidogrel, reparixin and anti-CXCL7 to murine subjects. However, these few examples fail to provide adequate written description for administering a genus of any aneurysm inhibitors to the genus of any subjects for the purposes of administering anti-aneurysm treatment.
In this case, the specification fails to describe any identification of structural characteristics or properties of any aneurysm inhibitors, and how the administration of said genus of any aneurysm inhibitors to the genus of any subjects can deliver beneficial outcome for anti-aneurysm treatment. Regarding claim 6, the specification fails to describe a genus of derivative thereof of clopidogrel, which encompasses as small a derivative as an atom from clopidogrel, and how such broad genus of any derivatives thereof can be used to treat aneurysm in any subjects.
While M.P.E.P. section 2163 acknowledges that a single species can describe a genus, it also acknowledges that for a genus that encompasses widely variant species, disclosure of a single species within the genus fails to adequately describe all members of the genus. Please refer to the M.P.E.P. section 2163.05 [R-7.2022] under I, B for more details with respect to sufficient number of representative species that should be disclosed to describe a widely variant genus.
Given the lack of additional representative species of a genus claimed methods encompassing administering a genus of any aneurysm inhibitors to a genus of any subjects, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112(a) published in the Official Gazette and also available at www.uspto.gov.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-4 and 6-14 are rejected under 35 U.S.C. 103 as being unpatentable over Middleton et al. (The pro-inflammatory and chemotactic cytokine microenvironment of the abdominal aortic aneurysm wall: A protein array study, Journal of Vascular Surgery, Volume 45, Issue 3, March 2007, Pages 574-580, see IDS) in view of McPherson et al. (US Patent Application Publication No. 2007/0224643 A1 published 09/27/2007, see IDS), Matsumoto et al. (Antiplatelet Therapy for Prevention of Thromboembolic Complications Associated with Coil Embolization of Unruptured Cerebral Aneurysms, Drugs R D 2012; 12 (1): 1-7), Bernhagen et al. (WO 2009/117710 A2), and KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007).
The instant claims are drawn to a method of treating an aneurysm in a subject in need thereof, comprising a) measuring, in a biological sample of the subject, an expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22; b) identifying the subject as having an aneurysm if the expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22 is increased relative to a first reference sample; and c) administering an effective amount of an aneurysm inhibitors to the subject. See above 112(b) rejection for the claim interpretation.
Middleton et al. teach a method of measuring the expression level of cytokines, i.e., inflammatory mediators, implicated in abdominal aortic aneurysm (AAA) pathogenesis, specifically I-309, IL-1 alpha, MCP-1, MCP-2, MCP-3, MIP-1 delta, MIG, RANTES, IL-12 in a biological sample, i.e., homogenized human aortic tissue, (see Abstract and Fig. 1 & 2 on pages 576-577), identifying the human patients with increased expression level of said cytokines relative to control.
Middleton et al. do not teach administration of an aneurysm inhibitor, clopidogrel and reparixin; and the use of blood sample.
McPherson et al. teach a method of diagnosing a subject suspected of aneurysm by measuring panels of inflammatory markers, specifically including MCP-1 (see para [0031]) and uPAR (see para [0028]) in blood, serum, plasma, CSF, etc. (see para [0056]) comparing it to control and identifying patients with aneurysm, and treating the patients and/or monitoring the course of a treatment regimen (see all examples and claims).
Matsumoto et al. teach a method of treating cerebral aneurysm in human subjects by administering oral dose of clopidogrel 75 mg/day (see abstract and Fig. 1-4), and demonstrates that administering clopidogrel to patients with unruptured cerebral aneurysms was conventional standard practice.
Bernhagen et al. teach a method of treating AAA in a subject comprising administering reparixin (CXCR2 inhibitor) (see all claims, examples and Figures). Bernhagen et al. teach co-administration of glycoprotein IIB/IIIA antagonists (inhibitors)
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the instant application to practice the method taught by Middleton et al. and combine it with the use of blood samples as taught by McPherson while administering anti-aneurysm drugs clopidogrel, reparixin and/or glycoprotein IIB/IIIA antagonists as taught by Matsumoto et al. and Bernhagen et al. A POSITA would have motivated to practice such methods because the administration of aneurysm drugs clopidogrel, reparixin and/or glycoprotein IIB/IIIA antagonists were conventional practice especially for patients with AAA or cerebral aneurysm identified as having elevated levels of aforementioned cytokines as taught by Middleton et al., McPheron et al., Matsumoto et al. and Bernhagen et al.
As discussed in KSR International Co. v. Teleflex Inc., 550 U.S.--, 82 USPQ2d 1385 (2007), it is considered obvious to combine prior art elements known to be used in equivalent fields of endeavor together into a single combination. The reference clearly shows that the claimed methods were all practiced in the field of diagnosing aneurysm and its treatment.
A POSITA would have had a reasonable expectation of success to practice such methods because all of the required biochemical reagents and techniques were readily available and rampantly used as evidenced by Middleton et al., McPheron et al., Matsumoto et al. and Bernhagen et al. prior to the filing of the instant application.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
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 claim 1-18 of U.S. Patent No. 12553904. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Claim 1 of the instant application:
A method of treating an aneurysm in a subject in need thereof, comprising a) measuring, in a biological sample of the subject, an expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22; b) identifying the subject as having an aneurysm if the expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22 is increased relative to a first reference sample; and c) administering an effective amount of an aneurysm inhibitors to the subject. See above 112(b) rejection for the claim interpretation.
Claim 1 of ‘904 patent:
A method for treating a cerebral aneurysm in a human subject, the method comprising: administering an effective amount of an aneurysm inhibitor to the subject, wherein the subject has an increased protein expression level of one or more biomarkers selected from the group consisting of IL-11, IL-17, and Amphiregulin relative to a reference sample of a subject without aneurysm, and wherein the one or more biomarkers is determined in a blood sample, a serum sample, or a plasma sample.
The instant claim 1 and the claims of ‘904 differ in that claims of ‘904 patent recite biomarkers IL-11, IL-17, and Amphiregulin which are not present in the instant claims. However, the dependent claims uPAR (claim 2) and MCP1 (claim 6) of ‘904 recite overlapping biomarkers as claimed methods of the instant application, while comprising the overlapping scope of administering the same aneurysm inhibitors see claims 13-17 of ‘904 patent. Taken together, there is a significant overlap in scope of instant claims with the claims of ‘904 patent. For the reasons provided herein, claims 1-14 are rejected on the ground of nonstatutory double patenting to prevent the unjustified or improper timewise extension of said patent.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-8 of U.S. Patent No. 12016846. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Claim 1 of the instant application:
A method of treating an aneurysm in a subject in need thereof, comprising a) measuring, in a biological sample of the subject, an expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22; b) identifying the subject as having an aneurysm if the expression level of (i) I-309, IL-16, IL-1 alpha, MCP-2, MIP-1 delta, and/or uPAR, (ii) I-309, IL-16, MCP-4, MIP-1 delta, CXCL7/NAP-2 and/or uPAR, or (iii) FasL and/or CCL22 is increased relative to a first reference sample; and c) administering an effective amount of an aneurysm inhibitors to the subject. See above 112(b) rejection for the claim interpretation.
Claim 1 of ‘846 patent:
A method of clinically treating a subject with a cerebral aneurysm, comprising administering to the subject a therapeutically effective amount of a targeted platelet inhibitor selected from the group consisting of clopidogrel, reparixin, and a combination thereof, wherein the targeted platelet inhibitor is administered to the subject at least once a day and for at least one week.
The instant claim 1 and the claims of ‘846 differ in that claims of ‘846 patent do not recite a step of measuring expression levels of cytokines recited in the instant claims. However, the specification of ‘846 teaches the use of Raybiotech cytokine arrays which contain ALL of the cytokines listed in the instant claims, a method of measuring, identifying human patients with aneurysm and administering anti-CXCL7 antibody together with targeted platelet inhibitor selected from the group consisting of clopidogrel and reparixin (see all claims and specification of ‘846 patent). Therefore, it would have been obvious for a POSITA to practice the methods taught by ‘846 which directly overlap in scope with the instant claims. For the reasons provided herein, claims 1-14 are rejected on the ground of nonstatutory double patenting to prevent the unjustified or improper timewise extension of said patent.
Examiner Note:
Claim 5 is rejected under 35 USC 101 and 112, and double patenting. Claim 5 is NOT rejected under 103 rejection. The Examiner could not find any prior art that teaches or suggests administering anti-CXCL7 antibody as an aneurysm inhibitor.
Conclusion
Claims 1-14 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
The instant Office action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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