DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application, Amendments and/or Claims
2. The response dated 4/17/2026 is acknowledged and entered into record. Claim 1 is amended. Claims 1-12 are currently pending.
Election with traverse
3. Applicant’s election with traverse of Group I (claims 1-11), in the reply filed on 17 April 2026 is acknowledged.
4. Applicant’s election of the following species: a) Alzheimer’s disease as the “Neurodegenerative disease”; b) FABP3 and FABP5 as the “Biomarker combination”; c) Antibodies against each of FABP3 and FABP5 as the “Kit with antibodies”, in the reply filed on 17 April 2026 is also acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the (species) election has been treated as an election without traverse (MPEP § 818.01(a)).
5. The traversal is on the ground(s) that there is a special technical feature between Groups I and II. Applicant argues that the cited art (Cologna et al) discloses a model of Niemann-Pick disease, however, does not teach the diagnosis of at least one of the recited neurodegenerative diseases of amended claim 1, using the FABP3 and FABP5 combination. Applicant therefore, asserts that there is a “special technical feature between Groups I and II”, and requests the examination of claims 1-12 on the merits.
6. Applicant’s comments are considered, and are found to be persuasive. After further review and consideration of amendment of claim 1, the restriction requirement between Groups I and II, is withdrawn. Therefore, the non-elected Group II (claim 12), will be rejoined with the elected Group I.
7. In view of the withdrawal of the restriction requirement with respect to the rejoined inventions, applicant(s) are advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
8. The requirement is still deemed proper and is therefore made FINAL.
9. Claims 1-12, drawn to a method for detecting a neurodegenerative disease (ND) in a subject, and a kit comprising antibodies, are considered for examination in the instant application.
Claim Objection
10. Claims 1-2, 5-7, 10-12 are objected to because of the following informalities:
(i) Claims 1-2, 5-7, 10-12 recite acronyms FABP3, FABP5, GFAP, and NF-L,
which should be spelled out for clarity.
(ii) Claim 1 recites “a subject” in line 1, as well as “a subject” In the last line of the claim (emphasis added). Based upon the understanding, that said subjects of claim 1 are the same, it is suggested that the subject in the last line of claim 1, can be changed to “the subject” for clarity.
Appropriate correction is required.
Specification
11. The disclosure is objected to because of the following informalities:
A) Internet address:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see, for example, page 23, para 0091). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
B) Brief description of drawings:
Fig. 4 of the drawings have sections (A) to (I). The brief description in the specification (page 6) however, does not mention Fig. 4(G) to (I).
C) Abstract:
The Abstract is objected for stating “Selected Drawing: FIG. 1” following the ABSTRACT paragraph.
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
NOTE: It is suggested that the objection can be withdrawn by deleting “Selected Drawing: FIG. 1”.
Claim Rejections - 35 USC § 112-Second paragraph
12. 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.
13. 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.
14. Claims 2-5 and 7-10 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 pre-AIA the applicant regards as the invention.
15. Claims 2 and 7 are rejected under 35 U.S.C. 112, second paragraph, for reciting “a model”, which is unclear. Is the “model” referring to a mathematical/analytical model or an animal/disease cell model (as stated in para 0050, 0002 of the specification). For prior art purpose, either of the interpretations will be applied.
16. Claim 10 is rejected under 35 U.S.C. 112, second paragraph for being unclear and confusing. Claim 10 depends from claim 7 that recites comparing the evaluation value of a (test or experimental) subject (EV), with the evaluation value of a neurodegenerative patient (EVP). Claim 10 recites a SCORE based upon the concentration in a “subject”, and a “healthy subject”. It is not clear if the “subject” of claim 10 is a neurodegenerative disease subject, or is a (test or experimental) subject. Claim 10 fails to identify the metes and bounds of the related subject matter and how that could be ascertained in the stated invention.
17. Claims 3-5 and 8-9 are rejected as these depend from an indefinite claim and do not clarify the scope of patent protection sought.
18. Appropriate clarification and correction are required.
Claim Rejections - 35 USC § 112-Second paragraph and 35 USC §101
19. 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.
20. 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.
21. 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 therefor, subject to the conditions and requirements of this title.
22. Claim 11 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 pre-AIA the applicant regards as the invention.
23. Claim 11 recites the use of a combination of two comprising FABP3 and FABP5 “as biomarkers to examine at least one neurodegenerative disease …. consisting of …. Alzheimer’s disease…”, but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
24. Claim 11 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966) [MPEP 2173.05(q)].
Claim Rejections - 35 USC § 101
25. 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 therefor, subject to the conditions and requirements of this title.
26. Claims 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) a method comprising measuring levels of naturally occurring biomarkers (FABP3, FABP5) in a biological sample of a subject, and detecting ND in the subject. The combination of steps recited in the claims taken in totality, including the steps of further comprising measuring naturally occurring biomarkers selected from Tau, α-synuclein, Aβ-42, GFAP, NF-L in a biological sample of a subject (claim 6), are not sufficient to qualify as a patent-eligible practical application as the claim covers every substantial practical application of the judicial exception. The determining of ND in a subject, based upon the naturally present biomarker levels in the subject do not impose meaningful limits on the claim scope, so that others are not substantially foreclosed from using the judicial exception(s).
27. The claims recite steps in addition to the judicial exception(s) at a high level of generality such that substantially all practical applications of the judicial exception(s) are covered, for example measuring the recited biomarker levels and determining whether a subject is likely to have AD was known in the prior art. Hochstrasser et al, US 20070042425, 2/22/2007 teach the diagnosis of a disease such as AD, comprising detecting at least one polypeptide from E-FABP (FABP5), H-FABP (FABP3), GFAP, Neurofilament L (NF-L), in a body fluid sample from the subject (Abstract; para 0012, 0086). The inventive method as claimed is therefore, not patent-eligible.
28. The “determining” of ND in a subject also does not impose meaningful limits on the claim scope, so that others are not substantially foreclosed from using the judicial exception(s), as this is based upon an abstract idea or judgement that can be derived, i.e., by application of mathematical operation (model) for determining values or numbers (claims 2-4, 7-9), using mathematical formulas or equations (claims 5, 10), which demonstrate a law of nature. For example, Mouiha et al (J Alz Dis 30: 91-100, 2014) teach the relationship or association of biomarkers (e.g. Aβ-42, tau) and AD progression in vivo (Abstract) using samples from healthy and disease (AD) subjects (page 92, Methods, para 1; page 93, col 1, para 1), and applying mathematical models and plots comprising Z-scores (page 93, col 2, para 2; page 94, col 2, para 4; Fig. 2). The evaluation of results based upon observation and judgement is equivalent to mental processes or concepts performed in the human mind. The recited limitations including the step of comparing the values (between the subject and control (healthy)), are no more than a field of use or merely involve insignificant extra-solution activity to the judicial exception; e.g., data gathering, as the claimed biomarkers in a biological sample are naturally occurring polypeptides in healthy, and diseased subjects. Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 79, 101 USPQ2d 1961, 1968 (2012) (Mayo). Additionally, the step of comparing can be done wholly in one' s mind. See Univ. Utah and Myriad v. Ambry Genetic.
29. Dependent claim(s) 2-10 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 101 because the additional recited limitation(s) fail(s) to establish that the claim(s) is/are not directed to an abstract idea, for reasons stated above. Dependent claims 2-10, recite measuring the biomarker levels in a biological sample of a subject and diagnosing AD, which are known in the art. Looking to the claims as a whole, none of the steps considered individually or in combination include additional elements that are sufficient to amount to significantly more than the judicial exception, abstract idea and ineligible mental steps, because the claimed steps are routine, conventional and must necessarily be performed in order to detect a known neurodegenerative disease utilizing well established natural biomarkers as recited in claims 2-10. Thus, the claims are directed to patent ineligible subject matter. Bilski v. Kappos, 75 Fed. Reg. 43922, July 27, 2010 (2010 Interim Bilski Guidance).
Claim Rejections - 35 USC § 102
30. 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.
31. Claims 1-3, 6, and 11-12 are rejected under AIA 35 U.S.C. 102(a)(1) as being anticipated by Hochstrasser et al, US 20070042425, 2/22/2007 (IDS).
32. The claims are directed to a method for a detecting a ND such as Alzheimer’s disease (AD) in a subject, comprising measuring levels of biomarkers FABP3 and FABP5 in a biological sample of a subject (claim 1), and further applying or converting the levels to a model to produce an evaluation value (EV) as an index for detecting a ND, and determining whether the subject is “likely to have” a ND, by comparing the EV of the subject with a reference value (RV) (claim 2), the determining comprising that the EV of the subject (EVS) is higher than the EV of a healthy subject (EVH) (claim 3), wherein: the method further comprises measuring a level of one or biomarkers listed in claim 6. Claim 11 recites the use of a combination of FABP3 and FABP5 as biomarkers to examine AD, and claim 12 recites a kit comprising antibodies against FABP3 and FABP5 for examination of AD.
33. Hochstrasser et al teach diagnosis of a brain damage-related disorder or a possibility thereof in a subject (likely to have), comprising detecting at least one polypeptide from E-FABP (FABP5), H-FABP (FABP3), GFAP, Neurofilament L (NF-L), in a body fluid sample from the subject (Abstract; para 0012), wherein the body fluid is CSF, serum, etc. and the brain-damage related disorder includes Alzheimer’s disease (para 0015, 0086) (instant claims 1, 6). The reference teaches differential content (levels) of the polypeptides in a subject with brain-damage related disorder (EV) and non-brain damage related disorder (RV or EVH), and uses a method to determine if the EV level is consistent with diagnosis (likely to have) of a brain-damage related disorder (para 0013) (instant claim 2), wherein the method comprises an antibody for the detection and determination of the (FABP) concentration (levels) (para 0014). Since the reference teaches that the polypeptides are “differentially contained” in a subject with brain-damage related disorder (EV) and non-brain damage related disorder (RV), the reference inherently teaches “comparing” the levels of EV and RV (of instant claim 2). With regards to the limitation “applying … levels ….to a model” of instant claim 2, a model according to the instant specification “refers to a mathematical expression” (para 0050). Hochstrasser et al teach determining a significant difference (emphasis added) of the polypeptide level (i.e. applying statistical (mathematical) expression) in affected (likely to have disease), and non-affected samples (test sample or with reference or evaluation value of a healthy subject) (para 0145). The reference also teaches that the diagnosis can be made on the basis of the polypeptide levels or amount (in the sample) being significantly higher or lower (smallest numerical difference) than a comparative test sample (a non-affected sample, which corresponds to reference value or an evaluation value of healthy subject) (para 0145). The reference therefore, clearly uses mathematical expression representing a model (instant claims 2, 3). Hochstrasser et al teach the use of a combination of polypeptides comprising E-FABP and H-FABP for diagnostic and therapeutic applications related to brain damage-related disorders (to examine at least one ND) (para 0027) (instant claim 11). The reference teaches an assay device for diagnosis of brain-related disorders comprising one or more antibodies that binds to E-FABP, H-FABP, wherein the device is a kit (para 0037, 0048, 0050, 0053, 0068, 0148). (instant claim 12). Hochstrasser et al therefore, anticipate the instantly recited method.
Claim Rejection - 35 USC § 103
34. 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.
35. Claims 1-4, 6-9 and 11-12, are rejected under AIA 35 U.S.C. 103 as being unpatentable over Hochstrasser et al (2007), in view of Mouiha et al (J Alz Dis 30: 91-100, 2014).
36. Claim 4 recites the determination of AD in a subject further comprising comparing the EV of the subject with the EV of an AD patient, and determining that the subject is likely to have a disease with the smallest numerical difference between EV of the subject and EV of AD. Claim 7 recites further comprising applying and/or converting one or more of the recited biomarkers (of claim 6) in addition to FABP3 and FABP5 to a model to produce an EV as an index to detect a ND, and determining the likelihood of having ND in the subject by comparing an EV of the subject with the EV of an AD patient; and determining the likelihood of AD when the EV of the subject is equal to or higher than that of an AD patient (claim 8). Claim 9 recites determining that the subject is likely to have AD with the smallest numerical difference between the EV of the subject and that of an AD patient.
37. The teachings of Hochstrasser et al are set forth above.
38. Hochstrasser et al do not the comparison of EV or levels of the test subject with levels or EV of a diseased or an AD patient.
39. Mouiha et al teach the relationship or association of biomarkers (e.g. Aβ-42, tau) and changes or progression of AD in vivo (Abstract), using mathematical models (page 93, col 2, para 2) and z-scores for each biomarker (page 94, col 2, para 4). The reference teaches the inclusion of samples from healthy (normal aging) and disease (AD) subjects (page 92, Methods, para 1; page 93, col 1, para 1). Mouiha et al teach that the addition of more biomarkers from samples collected from normal aging and AD subjects is required “to achieve scientific accuracy and statistical validity” collected from “samples representing a full spectrum of the disease” (Methods, para 1). Even though Mouiha et al do not use the term EV, the reference uses a mathematical model to obtain values for comparing the biomarker data in subjects (page 94, col 2, para 4). As the values are derived from a model, and are used in the “comparison and interpretation of different biomarkers in subjects”, the values would necessarily correspond to instant EV, absent any evidence to the contrary. (instant claims 4, 7-9).
40. It would therefore, have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art, to modify the method of detecting AD in a subject by comparing the EV of the subject with that of a healthy subject as taught by Hochstrasser et al, by also including and comparing the subject EV with that of AD subjects in view of the teachings of Mouiha et al. The person of ordinary skill would have been motivated to include the diseased (AD) samples, “to achieve scientific accuracy and statistical validity” obtained from “samples representing a full spectrum of the disease” (Mouiha et al). The person of ordinary skill would have expected reasonable success, because diagnostic studies using different biomarkers and their application to various models were ongoing, at the time of filing of the instant invention.
41. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
Conclusion
42. No claims are allowed.
43. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aditi Dutt whose telephone number is (571)272-9037. The examiner can normally be reached on M-F 9:00am-5:00pm.
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45. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker, can be reached on 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A. D./
Examiner, Art Unit 1675
27 June 2026
/KIMBERLY BALLARD/
Primary Examiner, Art Unit 1675
Prosecution Insights