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 .
Claim Status
The preliminary amendments filed 8/25/23 are acknowledged. Claims 1-2 and 10 are cancelled. Claims 5 and 7-9 are amended. Claims 3-9 are pending. Claims 3-9 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statement filed on 8/25/23 has been considered. A signed copy is enclosed.
Applicant is advised that the listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report will not be considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they will be considered.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 3-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claims are directed to a method for testing for mild cognitive impairment in a subject using Claudin-5 in a body fluid collected from the subject as an indicator. The method can comprise distinguishing mild cognitive impairment from a group of diseases consisting of Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, obsessive-compulsive disorder, and bipolar disorder. The method can comprise measuring the amount of Claudin-5 in the body fluid collected from the subject and the fluid can be measured using an anti-Claudin-5 antibody. The method can be performed with a subject suspected of having cognitive impairment, and the method can be “characterized by” being combined with one or more of a variety of medical procedures.
The claims recite a method without describing steps that can identify “mild cognitive impairment” or distinguish “mild cognitive impairment” from other diseases and disorders. The only step recited “uses” Claudin-5 from a body fluid. There is no identification of whether the Claudin-5 is detected or measured or which controls are needed to make any specific determination from the “use” of the biomarker. Further, there is no identification of any steps that allow for correlation to any disease state, or that rule out any disease state. Therefore, there is no structure that correlates with the required function of the claimed invention. The examples in the instant specification describe an immunoassay using an anti-claudin-5 antibody, which results in a quantification system using a sandwich ELISA. This assay was used to detect amounts of Claudin-5 in sera derived from patients with central nervous system diseases. The test samples were compared to control samples from healthy individuals. The study was retrospective, and used patients that were already diagnosed with various neurological diseases or mild cognitive impairment. No study was performed in a prospective manner demonstrating that any measurement or detection of Claudin-5 was used to diagnose a patient with any condition. The specification also did not identify clear thresholds or specific assays, or the controls necessary to establish such a diagnosis. No clear description of steps for distinguishing diseases has been presented in the specification or in the claims. The specification does not set forth a representative number of species for the breadth of the claimed genus of methods.
The instant claims do not fully describe the required method, or present any form of specific threshold or other standards that would allow the method to achieve the required function. The specification provides no specific description of the steps involved, other than a generic introduction of possible assays that may work in the intended method. The specification further does not establish a reasonably specific threshold measurement, or specific units for the threshold, that would allow the Claudin-5 to be “used” for mild cognitive impairment. Thus the method described by the instant specification encompasses an overly broad genus, and there is no correlation between the steps of the method and the functional outcome. Therefore, the specification provides insufficient written description to support the genus encompassed by the claims. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
The skilled artisan cannot envision the steps, specific assay methods and specific measurement thresholds that are required to establish specific status outcomes. In general, the art regarding establishing biomarkers is unpredictable. Waiker et al (J Am Soc Nephrol. 2012 January; 23(1): 13–21) teach that although diagnostic tests are judged based on their ability to classify individuals according to disease status, the actual disease status is often not known with certainty in clinical medicine. It is also important to note that Waiker et al discuss the necessity of specific thresholds. Waiker et al describe that the measurement is common in medical practice, but the test can result in misclassification of disease status, and this may be specifically due to exclusion of certain intermediate values that may have led to an overestimation of the accuracy of other biomarkers. This indicates that the threshold established for any given biomarker to describe any particular disease is critical for establishing the accuracy of the biomarker to predict disease (see page 8). The instant disclosure fails to resolve the specific methods, the specific thresholds, or the correlation of Claudin-5 with any specific disease state. Because the genus may be so highly variant, the examples provided, as well as the generic terms of “using” Claudin-5 and “testing for mild cognitive impairment” are insufficient to describe the genus, even when considered in light of the general knowledge in the art.
Further, Mayeux (NeuroRx. 2004 Apr;1(2):182-8) teaches that while biomarkers provide a dynamic and powerful approach to understanding a spectrum of diseases, variability is a major concern in biomarkers (see abstract). Biomarkers are subject to critical timing regarding sample collection, storage conditions, and adequate laboratory handling (see Table 2). Further, normal ranges are often difficult to establish, given interindividual variability, tissue localization, reliability of the biomarker measurements, and persistence of the biomarker (see pages 187-188). This would make comparison to establish disease or select treatment highly unpredictable.
Applying surrogate markers to diagnosis of neurological diseases is particularly unpredictable. For example, Scholl et al (Scholl et al. Challenges in the practical implementation of blood biomarkers for Alzheimer’s disease; The Lancet Healthy Longevity; 2024; 5) teach that the challenges include understanding the effect of pre-analytical and analytical conditions, potential confounding factors, and comorbidities that could influence outcomes of blood biomarkers and their use in diverse populations (see e.g. abstract). Additionally, distinct scenarios present their own specific challenges (see e.g. abstract). In memory clinics, the successful integration of blood biomarkers in diagnostic tests will require well-established diagnostic accuracy and comprehensive assessments of the effect of blood biomarkers on the diagnostic confidence and patient management of clinicians (see e.g. abstract). In primary care settings, and even more when implemented in population-based screening programs for which no experience with any biomarkers for Alzheimer’s disease currently exists, the implementation of blood biomarkers will be challenged by the need for education of primary care clinical staff and clear guidelines (see e.g. abstract).
Similarly, Milner et al (Multidimensional digital biomarker phenotypes for mild cognitive impairment: considerations for early identification, diagnosis and monitoring. Front. Digit. Health 6:1265846) teach that Mild Cognitive Impairment (MCI) poses a challenge for a growing population
Worldwide (see e.g. page 01). Early identification of MCI is critical to providing the right interventions at the right time to maximize an individual’s quality of life (see e.g. page 01). However, MCI is not a definitive diagnosis, and represents an “in-between” condition between normal aging and early dementia (see e.g. page 02). Unlike conditions such as a bone fracture for which a definitive diagnosis can be made using imaging, it is more complex to determine whether decline in an individual’s cognitive function is indicative of MCI (see e.g. page 01). Predictive factors of increased future risk of experiencing MCI can also be difficult to isolate (see e.g. page 01). Yet no gold standard currently exists to predict or identify MCI and traditional biomarkers such as imaging, genes or blood work have been used with mixed results (see e.g. page 01). Validating biomarkers for MCI, whether traditional or digital, is a significant undertaking and more complex with novel biomarkers or biomarker phenotypes (see e.g. page 03). Algorithmic gold standards for identifying MCI or predicting the transition between MCI and dementia are to date lacking (see e.g. page 03).
The teachings of Hou (What Are the Reliable Plasma Biomarkers for Mild Cognitive Impairment? A Clinical 4D Proteomics Study and Validation, Mediators of Inflammation, 2024, 7709277) support the unpredictability of biomarkers for mild cognitive impairment. Hou teaches that there is currently no gold standard for the diagnosis of MCI (see e.g. page 2, left column). The main diagnostic methods include neuropsychological assessment, imaging, and fluid testing, and their use depends on the clinician’s knowledge of MCI (see e.g. page 2, left column).
Applicant is advised that according to MPEP 2163, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-9 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.
The term “mild” in claims 3 and 4 is a relative term which renders the claim indefinite. The term “mild” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the specification does describe means to identify potential “mild” cognitive impairment, the definition does not set any sort of threshold to distinguish “mild” cognitive impairment from moderate or severe cognitive impairment. The term “mild” is therefore dependent on the practitioner and is a relative term.
In claim 3, the phrase “using Claudin-5 in a body fluid collected from the subject as an indicator” renders the claim indefinite. It is unclear if the term “using” is intended to refer to a method step, and it is also unclear exactly what the Claudin-5 is “indicating.” Neither of these terms are defined in the specification and therefore are indefinite. Furthermore the claims do not even describe what characteristic of the Claudin-5 must be present to “indicate” disease state.
In claim 3, the phrase “using Claudin-5 in a body fluid collected from the subject as an indicator” renders the claim indefinite. It is unclear whether the method requires purifying Claudin-5 from the blood to “use” it, or if the “using” is indicating detection of the Claudin-5. Therefore the scope of the claim is indefinite.
In claim 6, the phrase “using an anti-Claudin-5 monoclonal antibody” renders the claim indefinite. It is unclear what criteria must be met to be considered “using” the monoclonal antibody. For example, must the antibody detect the Claudin-5, produce a signal, bind the Claudin to a support, or some other feature? The scope of the term “use” is therefore indefinite.
In claim 9, the phrase “characterized by being combined with” renders the claim indefinite. It is unclear if “characterization” requires that a specific step is performed, or if the mere possibility of conducting an additional measurement is sufficient to meet the limitations of the claim.
In claim 9, the phrase “combined with one or more diagnoses” renders the claim indefinite. The claim recites species of measurements or medical tests, not diagnoses. It is unclear whether the claim requires diagnosis of a disease state, or measurement using one of the named procedures.
In claim 9 the phrase “with the proviso that a medical practice is excluded” renders the claim indefinite. The term “medical practice” is not defined by the instant specification, and the criteria for defining which events constitute a “medical practice” are not set forth. Furthermore, the list of procedures in claim 9 could potentially be considered “medical practices,” because they involve medical procedures performed on a subject. Therefore, the scope of the term “medical practice” is indefinite.
Claims depending from the rejected claims do not remedy the deficiency and therefore are also rejected.
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 therefor, subject to the conditions and requirements of this title.
Claims 3-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements, which are recited at a high level of generality, provide conventional assays and samples that do not add meaningful limits to practicing the law of nature and abstract idea.
The Supreme Court in Mayo laid out a framework for determining whether an applicant is seeking to patent a judicial exception itself, or a patent-eligible application of the judicial exception. See Alice Corp., 573 U.S. at 217-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. 66, 101 USPQ2d 1961). See MPEP 2106. The first step of the analysis asks whether the claimed invention is directed to a statutory category of invention. The instant claims recite a method for testing for mild cognitive impairment in a subject using Claudin-5 in a body fluid collected from the subject as an indicator. The instant specification does not define “using…as an indicator.” The claims are therefore given their broadest reasonable interpretation, which is that the claims read on diagnostic methods. The dependent claims require measurement of the amount of Claudin-5 in a body fluid, potentially with an anti-Claudin-5 monoclonal antibody. The claim is therefore directed to a method, which is a statutory category of invention.
Second, the claimed invention also must qualify as patent-eligible subject matter, i.e., the claim must not be directed to a judicial exception unless the claim as a whole includes additional limitations amounting to significantly more than the exception (see MPEP 2106). Based upon an analysis with respect to the claim as a whole, the instant claims are determined to be directed to a law of nature/natural principle and an abstract idea. The relationship between the recited biomarkers and mild cognitive impairment is a natural principle, which is a judicial exception. This method describes correlation of a particular biomarker with a particular natural disease state, which is comparable to concepts identified by the Supreme Court in Mayo. (see Mayo 101 USPQ2d at 1966). The use of the biomarkers and correlation with disease could be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Further, the decision-making required to identify mild cognitive impairment from any characteristic of Claudin-5 in a body fluid is a mental process that can be performed in the human mind (see e.g. MPEP 2106.04(a)). Claims to comparison of data, such as the measurements for Claudin-5, to determine existence of alteration, can practically be performed in the human mind, which means they fall within the judicial exception of abstract ideas (see e.g. MPEP 2106.04(a)).
Third, a claim that focuses on the use of a natural principle must also include additional elements or steps to show that the inventor has practically applied, or added something significant to, the natural principle itself. See Mayo 101 USPQ2d at 1966. Adding steps to a natural biological process that only recite well-understood, routine, conventional activity previously engaged in by researchers in the field would not be sufficient. See id. At 1966, 1970. The claims identifies sample types for testing, subjects to be tested, conventional reagents (e.g. monoclonal antibodies) and well-known assays for determining biomarker expression levels. The identification of sample types and subjects from which the samples are to be collected is routine in the art of medical testing. As stated in MPEP 2106.05(d), the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Determining the level of a biomarker in blood by any means has been determined as one of the well-understood, routine, conventional activity: see Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). Therefore, the additional features of the claims (i.e., measuring the level of the recited biomarkers, and identifying the source of the sample for screening) do not ensure that the claims amount to significantly more than the natural principle itself. The claims use conventional means to observe a natural correlation and therefore the steps of the claimed methods are not sufficient to transform unpatentable natural correlations into patentable applications of those regularities. This is also supported by the findings of the in Ariosa Diagnostics, Inc. v. Sequenom, Inc., 115 USPQ2d 1152 (Fed. Cir. 2015), wherein the Federal Circuit held that claims that measure biological substances using methods that are routine and conventional do not amount to more than reliance on a correlation that is a law of nature for patentability.
The question of whether identification of the patient population amounts to significantly more than the judicial exception is addressed in Mayo Collaborative Serv. v. Prometheus Labs., Inc., 566 U.S. _, 132 S. Ct. 1289, 1293-94, 101 USPQ2d 1961, 1965-66 (2012) (citing Diehr, 450 U.S. at 187, 209 USPQ at 7), when the Supreme Court determined that process claims reciting a correlation may inhibit further discovery by improperly tying up future use of laws of nature, even though the laws of nature at issue are narrow laws that may have limited applications. After measurement of the correlation, the claims can tie up a doctor's subsequent treatment decisions, whether treatment does or does not change in light of inference the doctor has drawn using disclosed correlations, since the claims threaten to inhibit development of more refined treatment recommendations that combine the patentee's correlations with later discovered features, and since the correlation step of the claims is set forth in highly general language covering all processes that make use of the correlation. Further, the steps simply refer to a relevant patient population, which is a pre-existing audience; doctors wish to determine whether a particular patient has a disease, or if the disease has/has not progressed. The claims inform a relevant audience about certain laws of nature; and additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community, and those steps, when viewed as a whole, add nothing significant beyond the sum of the parts taken separately. Even though the laws of nature at issue are narrow laws that may have limited applications, the claim does not amount to significantly more than the natural law itself.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 3-9 is/are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Spetzler et al (US 2014/0141986 A1; filed 2/17/12; published 5/22/14).
The instant claims are directed to a method for testing for mild cognitive impairment in a subject using Claudin-5 in a body fluid collected from the subject as an indicator. The method can comprise distinguishing mild cognitive impairment from a group of diseases consisting of Parkinson’s disease, multiple sclerosis, Alzheimer’s disease, obsessive-compulsive disorder, and bipolar disorder. The method can comprise measuring the amount of Claudin-5 in the body fluid collected from the subject and the fluid can be measured using an anti-Claudin-5 antibody. The method can be performed with a subject suspected of having cognitive impairment, and the method can be “characterized by” being combined with one or more of a variety of medical procedures.
Regarding the limitations of instant claim 3-4 and 8, Spetzler describes use of biomarkers in diagnostic, therapy-related or prognostic methods to identify phenotypes, such as a condition or disease, or the stage or progression of a disease (see e.g. abstract). This method can involve identifying a novel biosignature for the diagnosis, prognosis, or theranosis of a phenotype, using vesicles isolated from a subject (see e.g. paragraph [01203]). Diagnosis inherently indicates that a distinction has been made between disease types. Differences between biosignatures in a test subject and a control subject can be used to identify subjects that have the phenotype or disorder (see e.g. paragraph [01203]). The phenotype can be a neurological disorder (see e.g. paragraph [01207]). The neurological disorder can be mild cognitive impairment (see e.g. paragraph [1189]). The biomarkers used in the biosignature can be those in Table 5 (see e.g. paragraph [01208]), and Table 5 specifically lists Claudin-5 (see e.g. page 65).
Regarding the limitations of claims 5-6, Spetzler teaches that detection can occur through a binding agent such an antibody (see e.g. paragraph [0247]-[0248], [1306]), such as a monoclonal antibody (see e.g. paragraph [0252]). Spetzler teaches that the method comprises determining the presence, amount, or concentration of one or more biomarkers in the sample (see e.g. paragraph [0329]).
Regarding the limitations of instant claim 7, Spetzler anticipates comparing the level of the biomarker with healthy controls (see e.g. paragraph [0166], [0340]).
Regarding the limitations of instant claim 9, the method of Spetzler can include measurement of Amyloid beta to test for Alzheimer’s disease (see e.g. paragraph [0652], [1180], [1195]).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA MCCOLLUM whose telephone number is (571)272-4002. The examiner can normally be reached 9:00 AM to 6:00 PM EST.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, VANESSA FORD can be reached at (571)272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANDREA K MCCOLLUM/Examiner, Art Unit 1674
Prosecution Insights