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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/31/2025 has been entered.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/JP2019/013959, filed 03/29/2019. Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. PCTJP2018013571, filed on 03/30/2018 in Japan.
Status of the Claims
Claims 1-2, 5-7 and 9-19 are pending in the application. Claims 1 and 2 are amended, claims 5-6 and 11-19 are withdrawn and claims 3-4, 8, and 20 are cancelled. Claims 1, 2, 7, and 9-10 are pending and examined below.
Information Disclosure Statement
The information disclosure statement (IDS) filed 04/29/2026 has been considered, initialed, and is attached hereto.
Withdrawn Objections
The objections to the claims have been withdrawn due to the amendment of claims 1 and 2 and the cancellation of claim 20.
Withdrawn Rejection
The rejection of claim 2 under 35 USC § 112(a) is withdrawn due to the amendment of the claim.
The rejection of claims 1, 2, 3, 7, 9-10, and 20 under 35 USC § 112(b) is withdrawn due to the amendment of claims 1 and 2. Claims 3 and 20 are cancelled.
See new rejection under 35 USC § 112(b) below.
The rejection of 1, 2, 3, 7, 9-10, and 20 under 35 USC § 101 is withdrawn due to the amendment of claims 1 and 2. Claims 3 and 20 are cancelled.
The rejection of claims 1-2, 7, and 9-10 under 35 USC § 102 has been withdrawn due to the amendment of the claims.
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.
Claim 1 is 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.
Claim 1 recites a sample “from a subject suspected of having aortic aneurysm”. Claim 1 is indefinite because the claim does not distinctly claim “a subject suspected of having aortic aneurysm”. The disclosure does not recite any criteria, indicators, or symptoms of aortic aneurysm and it is therefore unclear what subjects would fall within the category of a subject “suspected of having aortic aneurysm”.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7, and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Swagemakers et al., US20110059089, 03/10/2011 (see PTO-892, 06/21/2024) as evidenced by NCP2 Blast SEQ ID No 1 (06/10/2026).
Regarding claim 1, Swagemakers teaches a method of detecting proteins in atherosclerotic plaque samples that differ in subjects that have suffered a cardiovascular event prior to or following the moment of sampling compared to subjects who have not suffered a cardiovascular event. Swagemakers further teaches that such biomarkers can be used for risk stratification, patient selection (for clinical trials), or monitoring of disease (Swagemakers, page 1, see entire paragraph [006]). Swagemakers further teaches that the cardiovascular event is selected from a list comprising rupture of an aortic aneurysm (Swagemakers, page 2, paragraph [0016], lines 4-5). Swagemakers further teaches that a biomarker comprises at least one protein that is a member of a group comprising Niemann-Pick Disease Type C2 (applicant’s elected species; Swagemakers, page 3, paragraphs [0021] and [0024]). Swagemakers further teaches obtaining a sample and that suitable samples include serum and plasma (Swagemakers, page 10, paragraph [0155], lines 2-6). Swagemakers further teaches a kit of parts for performing the methods comprising a detectable binding partner of the biomarker, for instance an antibody that binds specifically to the biomarker (Swagemakers, page 11, see entire paragraph [0167]). Swagemakers further teaches measuring the amount of at least one protein using analytical methods for showing the presence and/or concentration of a protein in a sample, e.g. by immunoassay analysis (Swagemakers, page 5,paragraph [0065], lines 4-8).
Swagemakers fails to teach that the subject is suspected of having aortic aneurysm and further fails to explicitly teach that Niemann-Pick Disease Type C2 protein has the sequence of SEQ ID NO: 1.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to apply the method of Swagemakers of detecting Niemann-Pick Disease Type C2 in a patient suspected of having an aortic aneurysm because of the teaching of Swagemakers that the biomarkers of the invention can be used for selecting patients for clinical trials or monitoring disease in patients with cardiovascular events comprising aortic aneurysms. As such the teaching of Swagemakers comprises obtaining a sample from a subject suspected of having an aortic aneurysm.
Regarding the limitation that Niemann-Pick Disease Type C2 protein has the sequence of SEQ ID NO: 1, Swagemakers teaches a biomarker that is Niemann-Pick Disease Type C2. Niemann-Pick Disease Type C2 has the sequence of SEQ ID NO: 1, supported by NCP2 Blast SEQ ID No 1, providing evidence that amino acid sequence of SEQ ID NO:1 is identical with the amino acid sequence of Niemann-Pick Disease Type C2 protein and therefore the art teaches the limitation of the claim.
Regarding claim 7, Swagemakers further teaches that the cardiovascular event is selected from a list comprising rupture of an abdominal aortic aneurysm (Swagemakers, page 2, paragraph [0016], lines 4-5).
Regarding claim 9, Swagemakers teaches that the subject or patient is human (Swagemakers, page 8, paragraph [0125], lines 1-3).
Regarding claim 10, Swagemakers teaches that the step of measuring the amount of at least one protein is performed by using analytical methods such as mass spectrometry or immunoassay analysis (Swagemakers, page 5, see paragraph [0065]).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Swagemakers et al. in view of Moxon et al. (2011) “Proteomic analysis of intra-arterial thrombus secretions reveals a negative association of clusterin and thrombospondin-1 with abdominal aortic aneurysm”, Atherosclerosis, 219, 2, pages 432-439 (see PTO-892, 06/21/2024) as evidenced by TSP1 Blast SEQ ID No 3 (06/10/2026).
Regarding claim 2, Swagemakers teaches a method of measuring at least one biomarker comprising NCP2 in patients suspected of having an aortic aneurysm substantially as claimed.
Swagemakers further teaches that the biomarker of the invention comprises at least two proteins and that the skilled person will understand that addition of more proteins to the biomarker-profile may help improve the predictive value of the biomarker (Swagemakers, page 1, paragraph [0009], lines 1-6).
Swagemakers fails to teach a step measuring Thrombospondin 1 protein.
Moxon teaches a method of analyzing intra-luminal thrombus derived proteins to identify potential markers for abdominal aortic aneurysm (Moxon, page 432, Abstract, lines 1-6). Moxon further teaches measuring serum thrombospondin-1 in men with abdominal aortic aneurysm and found it significantly lower in men with aneurysm as compared to control (Moxon, page 438, ‘3.4. Association of serum Thrombospondin-1 and clusterin with AAA’, lines 7-11). Moxon further teaches quantifying Thrombospondin 1 in serum by Thrombospondin specific Enzyme Linked Immunosorbent Assay (ELISA; Moxon, page 434, ‘2.9. Patient cohorts and analysis of serum throbospondin-1 and clusterin’, lines 5-7).
Regarding the limitation that Thrombospondin protein has the sequence of SEQ ID NO: 3, Moxon teaches a biomarker that is Thrombospondin 1. Thrombospondin 1 has the sequence of SEQ ID NO: 3 supported by TSP1 Blast SEQ ID No 3, providing evidence that amino acid sequence of SEQ ID NO:3 is identical with the amino acid sequence of Thrombospondin 1 protein and therefore the art teaches the limitation of the claim.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Swagemakers by also measuring Thrombospondin-1, as taught by Moxon, as an additional aortic aneurysm biomarker, in order to detect aortic aneurysm with improved predictive value. One of ordinary skill in the art would have been motivated to detect both Niemann-Pick Disease Type C2 and Thrombospondin 1 proteins in plasma or serum in view of the teachings of Swagemakers that the addition of more proteins to a biomarker-profile helps improve the predictive value of the biomarker and the teaching of Moxon that Thrombospondin 1 was significantly lower in men with aortic aneurysm compared to control.
The ordinary artisan would have a reasonable expectation of success, because both Swagemakers and Moxon teach detecting proteins in serum of patients and measuring them by immunoassay, and Moxon taught that Thrombospondin-1 expression is significantly reduced in patients with aortic aneurysm.
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 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 34 of copending Application No. 17/599,475 (reference application) in view of Keshamouni et al., US20150153346A1. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application similarly recites a method of detecting arteriosclerosis-related disease, including aortic aneurysm, comprising measuring Niemann-Pick Disease Type C2 and Thrombospondin 1.
Regarding claims 1 and 10, the copending ‘475 application teaches in claim 34 a method for detecting a concentration of an Niemann-Pick Disease Type C2 protein in a sample comprising obtaining a sample from a subject suspected of having arteriosclerosis-related disease, wherein the sample is selected from serum, plasma, or blood, measuring a concentration of Niemann-Pick Disease Type C2 protein having the amino acid sequence of SEQ ID NO: 1, wherein the arteriosclerosis-related disease comprises aortic aneurysm.
Copending claim 34 does not teach detecting aortic aneurysm.
Copending claim 34 also fails to teach preparing a measurement sample comprising a detection agent which binds Niemann-Pick Disease Type C2.
Copending claim 34 differs from instant claim 1 in that aortic aneurysm is recited as one of several possible “arteriosclerosis-related disease[s]” that may be detected. However, a reference that clearly names the same claimed species anticipates the claim no matter how many other species are named. See MPEP 2131.02(II).
Keshamouni teaches measuring the expression of a protein corresponding to a gene that is a cancer marker by immunoassay (Keshamouni, page 8, see paragraphs [0069-0070]). Keshamouni further teaches processing a patient sample (Keshamouni, page 5, paragraph [0044], lines 1-2) and that the cancer biomarker comprises one or more of a list of proteins and further one or more additional markers selected from a list comprising Niemann-Pick Disease Type C2 (claim 1; Keshamouni, page 4, paragraph [0037], lines 4-21). Keshamouni further teaches that Western Blot is a method to detect protein in a given sample and that proteins are probed using antibodies specific to the protein of interest, i.e. an immunoassay, in order to examine the amount of protein in a given sample and compare levels between several groups (Keshamouni, page 8, paragraph [0072], lines 6-9).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have used an immunoassay comprising a sample and an antibody specific for the protein of interest in the method of the copending application because of the teaching of Keshamouni that using antibodies specific to a protein of interest allows to examine the amount of protein in a given sample and compare levels between several groups.
The ordinary artisan would have a reasonable expectation of success because Keshamouni teaches detecting Niemann-Pick Disease Type C2 in a fluid sample as does the copending application.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 7-10 of copending Application No. 17/599,475 in view of Keshamouni et al., Moxon et al., and Swagemakers et al.
Regarding claim 2, claim 34 of the copending application and the prior art teaches an immunoassay method for detecting Niemann-Pick Disease Type C2 in a fluid sample from a subject suspected of having an aortic aneurysm substantially as claimed.
The copending application fails to teach also measuring Thrombospondin 1.
Moxon teaches a method of analyzing intra-luminal thrombus derived proteins to identify potential markers for abdominal aortic aneurysm (Moxon, page 432, Abstract, lines 1-6). Moxon further teaches measuring serum thrombospondin-1 in men with abdominal aortic aneurysm and found it significantly lower in men with aneurysm as compared to control (Moxon, page 438, ‘3.4. Association of serum thrombospondin 1 and clusterin with AAA’, lines 7-11). Moxon further teaches quantifying thrombospondin 1 in serum by ELISA (Moxon, page 434, ‘2.9. Patient cohorts and analysis of serum thrombospondin 1 and clusterin’, lines 5-7).
Swagemakers teaches a method of detecting aortic aneurysm by measuring Niemann-Pick Disease Type C2 protein. Swagemakers further teaches that the biomarker of the invention comprises at least two proteins and that the skilled person will understand that addition of more proteins to the biomarker-profile may help improve the predictive value of the biomarker (Swagemakers, page 1, paragraph [0009], lines 1-6).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the copending application of detecting Niemann-Pick Disease Type C2 protein in plasma or serum in order to detect aortic aneurysm, by also measuring the additional biomarker Thrombospondin 1, because of the teaching of Moxon that Thrombospondin 1 expression is significantly reduced in patients with aortic aneurysm and would have been motivated to do this in view of the teachings of Swagemakers that the addition of more proteins to a biomarker-profile helps improve the predictive value of the biomarker.
The ordinary artisan would have had a reasonable expectation of success, because the copending application as well as Moxon and Swagemakers teach detecting proteins as biomarkers related to aortic aneurysms in serum of patients and measuring them by immunoassay.
Claims 7 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 34 of copending Application No. 17/599,475 in view of Keshamouni and further in view of Isselbacher EM. (2005) “Thoracic and abdominal aortic aneurysms”, Circulation, 111, 6, pages: 816-828 (see PTO-892, 06/21/2024).
Regarding claim 7, claim 34 of the reference ‘475 application and the prior art teaches an immunoassay method for detecting Niemann-Pick Disease Type C2 in a fluid sample from a subject suspected of having an aortic aneurysm substantially as claimed.
However, the reference application does not specify that the aortic aneurysm is a thoracic aortic aneurysm, thoracoabdominal aortic aneurysm, and/or abdominal aortic aneurysm.
Isselbacher teaches that aneurysms of the aorta are evaluated and treated by physicians from a number of specialties and that cardiac surgeons operate on the ascending aorta and arch and vascular surgeons manage abdominal aortic aneurysms (Isselbacher, page 816, 1st paragraph, lines 1-4). Isselbacher further teaches that Thoracic aneurysms may involve the aortic root, ascending aorta, arch, or descending aorta (Isselbacher, page 816, 2nd paragraph, lines 1-3). As such, Isselbacher teaches that aortic aneurysms include thoracic aortic aneurysms and abdominal aortic aneurysms.
It would have been obvious to apply the method of detecting aortic aneurysm of the reference application to the specific known types of this condition, namely thoracic aortic aneurysms or abdominal aortic aneurysms, so that the patient could receive a diagnosis and timely intervention.
Regarding claim 9, claim 34 of the reference ‘475 application and the prior art teaches an immunoassay method for detecting Niemann-Pick Disease Type C2 in a fluid sample from a subject suspected of having an aortic aneurysm substantially as claimed.
However, the reference application does not specify that the subject is human.
Isselbacher teaches that most patients with thoracic aortic aneurysms are asymptomatic at the time of diagnosis because the aneurysms are typically discovered incidentally and that the feared consequence of thoracic aneurysms is aortic dissection or rupture which Is potentially lethal (Isselbacher, page 818, see ‘Clinical Manifestations’).
It would have been prima facie obvious to one of ordinary skill in to apply the method of detecting aneurysm of the reference application to humans because of the teaching of Isselbacher that most patients with a thoracic aortic aneurysm are asymptomatic and the consequences such as aortic dissection or rupture can be lethal.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
The rejections under 35 U.S.C. § 112(a), 112(b), 101, and 102 have been withdrawn due to the amendment of the claims and therefore the arguments are moot.
Applicant's arguments filed 10/31/2025 regarding the rejection under 35 U.S.C. § 103 have been fully considered but they are not persuasive.
Applicant argues, starting on page 12, that Swagemakers describes only that the proteins listed in Table I and/or Table II and/or Table III would be suitable “to be a plaque marker” and does not describe a serum, plasma, or blood marker.
This argument is not persuasive.
Although Swagemakers’ preferred embodiment is a sample that is an atherosclerotic plaque, Swagemakers does teach that suitable samples include serum and plasma. Put another way, Swagemakers teaches detecting biomarkers in serum or plasma and therefore meets the limitation of the claims.
Applicant further argues that Swagemakers merely indicates that Niemann-Pick Disease Type C2 protein in carotid plaque is included in more than 80 candidate plaque markers capable of predicting the risk of suffering from cardiovascular events but that not all 80 proteins have been investigated for the presence of a cardiovascular phenotype nor do all of them have a described phenotype.
This argument is not persuasive.
The claim is directed to measuring Niemann-Pick Disease Type C2 protein in a patient suspected of having an aortic aneurysm, Niemann-Pick Disease Type C2 protein having a cardiovascular phenotype is not a limitation of the claims and therefore the argument is not commensurate with the claims.
Applicant further argues on page 13, regarding the double patenting rejection, that independent claim 1, as amended recites sample preparation steps which are not recited in the copending ‘475 application and that moreover the prior art does not render the claims obvious.
This argument is not persuasive.
Claim 34 of the copending application recites a method of detecting Niemann-Pick Disease Type C2 protein in a patient suspected of having an aortic aneurysm as claimed. The copending application is silent on how to detect the protein. Even though the claims are not identical a double patenting rejection is appropriate because it would be obvious to have applied the immunoassay method of Keshamouni to detect Niemann-Pick Disease Type C2 protein for the reason as cited above.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEFANIE J KIRWIN whose telephone number is (571)272-6574. The examiner can normally be reached Monday - Friday 7.30 - 4 pm.
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/STEFANIE J. KIRWIN/Examiner, Art Unit 1677
/Soren Harward/Primary Examiner, TC 1600
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