DETAILED ACTION
Claims 1-13 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 11/20/2024, 11/25/2024, 02/28/2025, 01/12/2026, and 06/29/2026 have been considered by the examiner.
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.
1.Claims 1-13 are rejected under 35 U.S.C. 101 because the claimed product and method are directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Step 1
This part of the eligibility analysis evaluates whether the claim falls within any statutory
category per MPEP 2106.03.
Regarding claims 1-13, Example 43 of “2019 PEG” is particularly enlightening because the fact pattern of claim 1 of example 43 is most similar to the instant application claims 1-13.
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 1, the claim is directed
to a process, which is one of the statutory categories of invention as the claim recites “A
treatment method comprising: (a) calculating a ratio of C11 to C13 levels measured in a blood
sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3) to
identify the patient as having a non-responder phenotype; (b) administering a treatment to the
patient having a non-responder phenotype.” (Step 1: YES).
Similarly, instant claims 1-13 are directed to a method of quantifying active orexin A in a sample (Step 1: YES).
Similarly, instant claims 5-9 and 11 are directed to a method quantifying active orexin A and correlating the levels of active orexin A to the diagnosis of orexin A deficiency, a sleep disorder, a neurodegenerative disease, or a traumatic brain injury (Step 1: YES).
Step 2A, Prong 1: Does the claim recite a judicial exception?
This part of the eligibility analysis evaluates whether the claim recites a judicial
exception. As explained in MPEP 2106.04(II) and the October 2019 Update, a claim “recites” a
judicial exception when the judicial exception is “set forth” or “described” in the claim.
Regarding instant claims 1-13, Example 43 of the “2019 PEG” shows a similar fact pattern.
Regarding claim 1 in Example 43 of the “2019 PEG” and per Step 2A, prong 1, the claim
recites the judicial exception of “calculating a ratio of C11 to C13 levels measured in a blood
sample from a patient diagnosed with Nephritic Autoimmune Syndrome Type 3 (NAS-3)
to identify the patient as having a non-responder phenotype,” and according to broadest
reasonable interpretation (BRI), an arithmetic calculation of a division is required to obtain the
ratio of C11 to C13 that can be used to identify whether the patient has the non-respondent
phenotype.
Specifically, limitation (a) in claim 1 of Example 43 of the “2019 PEG” recites “calculating
a ratio of C11 to C13 levels measured in a blood sample from a patient diagnosed with Nephritic
Autoimmune Syndrome Type 3 (NAS-3) to identify the patient as having a non-responder
phenotype,” which has a BRI that requires performing an arithmetic calculation (division) in order to obtain the ratio of C11 to C13 levels, and then using this ratio to identify whether the
patient has the non-responder phenotype (i.e., the patient has a calculated ratio of 3:1 or
greater and thus is not responding, or will not respond, to glucocorticoids). This limitation
therefore recites a mathematical calculation. The grouping of “mathematical concepts” in the
2019 PEG includes “mathematical calculations” as an exemplar of an abstract idea. 2019 PEG
Section I, 84 Fed. Reg. at 52. Thus, limitation (a) falls into the “mathematical concept” grouping
of abstract ideas. In addition, this type of simple arithmetic calculation (division) can be
practically performed in the human mind, and is in fact performed in the human mind on a daily
basis, for instance by school-aged children studying mathematics. Note that even if most
humans would use a physical aid (e.g., pen and paper, a slide rule, or a calculator) to help them
complete the recited calculation, the use of such physical aid does not negate the mental nature
of this limitation. Thus, limitation (a) also falls into the “mental process” groupings of abstract
ideas.
In addition, limitation (a) describes a naturally occurring relationship between the ratio
of C11 to C13 and the non-responder phenotype, and thus may also be considered to recite a
law of nature. Accordingly, limitation (a) recites a judicial exception (an abstract idea that falls
within the mathematical concept and mental process groupings in the “2019 PEG”, and a law of
nature), and the analysis must therefore proceed to Step 2A Prong Two.
Similarly, instant claims 1-13 recite measuring naturally occurring active orexin A (protein) in a specimen, which is just looking at a natural phenomena, and thus is considered a law of nature.
Similarly, instant claims 5 and 11 recite measuring active orexin A (protein) and correlating the levels of the protein to orexin A deficiency, a sleep disorder, a neurodegenerative disease, or a traumatic brain injury and thus is considered a law of nature.
Similarly, instant claims 6 and 8-9 recite measuring active orexin A (protein) and correlating the levels of the protein to a neurodegenerative disease and thus is considered a law of nature.
Accordingly, instant claims 1-13 recite a judicial exception (law of nature), and the analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong 2: Does the claim recite additional elements that integrate the exception into a practical application?
Regarding instant claims 1-13, Example 43 of “2019 PEG” shows a similar fact pattern.
In claim 1 of example 43 of the “2019 PEG” and per Step 2A, prong 2, the claim as a whole does not integrate the recited judicial exception into a practical application of the
exception. This evaluation is performed by (a) identifying whether there are any additional
elements recited in the claim beyond the judicial exception, and (b) evaluating those additional
elements individually and in combination to determine whether the claim as a whole integrates
the exception into a practical application. Besides the abstract idea, the claim 1 of example 43
of the “2019 PEG” recites the additional element of “(b) administering a treatment to the patient
having a non-responder phenotype”. Although this limitation indicates that a treatment is to be
administered, it does not provide any information as to how the patient is to be treated, or what
the treatment is, but instead covers any possible treatment that a doctor decides to administer
to the patient. In fact, this limitation is recited at such a high level of generality that it does not
even require a doctor to take the calculation step’s outcome (the patient’s phenotype) into
account when deciding which treatment to administer, making the limitation’s inclusion in this
claim at best nominal. Thus, limitation (b) of example 43 of the “2019 PEG” fails to meaningfully
limit the claim because it does not require any particular application of the recited calculation,
and is at best the equivalent of merely adding the words “apply it” to the judicial exception.
Accordingly, limitation (b) of example 43 of the “2019 PEG” does not integrate the recited
judicial exception into a practical application and the claim is therefore directed to the judicial
exception.
Similarly, instant claims 1-13 do not have additional elements that would integrate
the judicial exception cited above into a practical application. In comparison to claim 1, Example
43 did not pass step 2A prong 2 with a step of general treatment. Instant claims 1-13 don’t even recite a treatment step. Example 43 failed with a step of a general treatment, instant
claims 1-13 do not recite a further active step, let alone a treatment.
Therefore, instant claims 1-13 do not integrate the judicial exception into a practical application.
Step 2B: Does the claim recite significantly more?
Regarding claim 1 of example 43 of the “2019 PEG” and per Step 2B, this part of the
eligibility analysis evaluates whether the claim as a whole amounts to significantly more than
the recited exception, i.e., whether any additional element, or combination of additional
elements, adds an inventive concept to the claim. MPEP 2106.05. As explained with respect to
Step 2A Prong Two, the claim recites a single additional element in limitation (b), which does
not require any particular application of the recited calculation and is at best the equivalent of
merely adding the words “apply it” to the judicial exception. Mere instructions to apply an
exception cannot provide an inventive concept (Step 2B: NO). The claim is not eligible.
Instant claim 1 recites “a step of contacting the specimen with a monoclonal antibody that recognizes the C- terminal side of orexin A to separate orexin A species; a step of digesting the separated orexin A species with a protease to obtain a peptide consisting of an amino acid sequence of SEQ ID NO: 1; and a step of performing mass spectrometry on the peptide”, which are merely instructions of obtaining a judicial exception and cannot be considered an inventive concept (Step 2B: NO).
Thus, claims 1-13 are rejected under 35 USC 101.
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.
2.Claims 1-5 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bingham et al., (WO2001000787A2).
Instant claim 1 recites “a method for quantifying active orexin A in a specimen, comprising: a step of contacting the specimen with a monoclonal antibody that recognizes the C- terminal side of orexin A to separate orexin A species; a step of digesting the separated orexin A species with a protease to obtain a peptide consisting of an amino acid sequence of SEQ ID NO: 1; and a step of performing mass spectrometry on the peptide”.
Bingham teaches a method for quantifying active orexin A in a specimen (see page 5 “It is another object of the invention to provide a diagnostic process comprising analyzing for the presence of Lig 72A or a variant thereof in a sample derived from a host suspected of at least one of the diseases”, see page 1 “Lig 72A is also referred to herein as "Orexin-A", see page 27 teaching measuring Lig 72A in a sample), assisting in diagnosis of a sleep disorder (see page 54-56 under “Example 11: Sleep Studies for Lig 72A”, see page 45 “The localization of Lig 72A in the Locus Coeruleus (nerve terminals) indicates that Lig 72A plays a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, sleep disorders; sleep apnea; narcolepsy…”) (instant claim 5), comprising:
a step of contacting the specimen with a monoclonal antibody that recognizes the C- terminal side of orexin A to separate orexin A species (see page 30 “An ELISA assay initially comprises preparing an antibody specific to an HFGAN72 receptor ligand, preferably a monoclonal antibody. In addition a reporter antibody generally is prepared that binds to the monoclonal antibody… To carry out an ELISA, a sample is removed from a host and incubated on a solid support, e.g., a polystyrene dish, that binds the proteins in the sample. Any free protein binding sites on the dish are then covered by incubating with a non-specific protein such as bovine serum albumin. Next, the monoclonal antibody is incubated in the dish during which time the monoclonal antibodies attach to any Lig 72A or a variant thereof attached to the polystyrene dish”);
a step of digesting the separated orexin A species with a protease to obtain a peptide consisting of an amino acid sequence of SEQ ID NO: 1 (see page 42 under “Example 4: Determination of Amino Acid Sequences of Lig 72A and Lig 72B”, see page 16 “Because Gln residues cannot be acetylated, and the N-terminus is blocked, the addition of only one acetate group indicates that the C-terminal sequence of a digested molecule is QK. In an alternative embodiment of the invention, the C-terminal sequence of a digested molecule is KK.”, see page 38 teaching SEQ ID No: 7 of Bingham being the same as SEQ ID No: 1 of the instant application); and
a step of performing mass spectrometry on the peptide (see page 42 “The sample was analyzed using nanoelectrospray ionization on a PE-Sciex triple quadrupole mass spectrometer…. This peptide was sequenced using collision induced dissociation (CID) tandem mass spectrometry (MS/MS).”) (instant claim 1).
Bingham teaches a step of purifying the peptide through solid-phase extraction methods before performing mass spectrometry (see page 57 “All of the Lig72A variant peptides shown in Table 3 were synthesized by the solid phase technique using 9-fluorenylmethoxycarbonyl (Fmoc) chemistry”) (instant claims 2 and 10). Bingham teaches a step of high-performance liquid chromatography before performing the mass spectrometry (see page 26 “Most preferably, high performance liquid chromatography is employed for purification.”) (instant claim 3 and 10). Bingham teaches wherein the separation of the orexin A species is performed through immunoprecipitation (see page 34 “Recombinant Lig 72A or a variant thereof is incubated with labeled or unlabeled cell extracts and immunoprecipitated with anti-Lig 72A antibodies. The immunoprecipitate is recovered with protein A-Sepharose and analyzed by SDS-PAGE. Unlabelled proteins are labeled by biotinylation and detected on SDS gels with streptavidin…”) (instant claims 4 and 10).
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.
3.Claims 6-9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Bingham et al., as applied to claims 1-5 and 10 above, in view of Kruse (WO 2018/078018 A2) (IDS filed on
The teachings of Bingham as it pertains to claims 1-5 and 10 are discussed in the 35 USC 102 above.
Bingham does not teach a neurodegerative disease being a synucleinopathy, being Parkinson’s disease, and the sample being cerebrospinal fluid.
Kruse teaches orexin-a assisting in the diagnosis of a neurodegenerative disease that is a synucleinopathy, which is Parkinson’s disease (see page 24 lines 34-35, see page 27 lines 11-17), wherein the sample is cerebrospinal fluid (see claim 7 of ‘018) (It is known in the art that orexin-a is also known as hypocretin-1, see page 5 lines 15-16) (instant claims 6-9 and 11).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the method of measuring active orexin A in a specimen taught by Bingham with the method of diagnosing Parkinson’s disease by measuring orexin A taught by Kruse. Kruse teaches that Parkinson’s is associated with abnormal levels of hypocretin-1 (also known as orexin-A) (see page 27 lines 11-17). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
4.Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Bingham et al., as applied to claims 1-5 and 10 above, in view of Liguori et al., “Sleep-Wake Cycle in Alzheimer's Disease Is Associated with Tau Pathology and Orexin Dysregulation.” Journal of Alzheimer's disease : JAD vol. 74,2 (2020): 501-508. doi:10.3233/JAD-191124.
The teachings of Bingham as it pertains to claims 1-5 and 10 are discussed in the 35 USC 102 above.
Bingham does not teach determining circadian rhythm.
Liguori teaches determining circadian rhythm in patients (see page 502 “alterations of circadian rhythmicity, particularly pronounced in patients with AD, tend to progress over the course of the disease”, see page 506 “the cognitive status (MMSE), and the CSF orexin levels further link the circadian dysfunction to the AD pathology in patients with mild to moderate AD.”) (instant claim 12).
It would have been obvious to one of ordinary skill in the art at the time of the instant application to combine the method of measuring active orexin A in a specimen taught by Bingham with the method of determining circadian rhythm in a patient with Alzheimer’s disease (AD) taught by Liguori. Liguori teaches that the dysregulation of the sleep-awake cycle in AD patients reflects the dysfunction of the circadian timing system (see page 505). Ligouri further teaches that the suprachiasmatic nucleus in the anterior hypothalamus, which is indicated as the main circadian clock, is connected with the pineal gland and has shown significant degeneration in the AD neurodegeneration (see page 505). The artisan would have reasonable expectation of success based on the cumulative disclosure of these prior art references at the time the instant application was filed.
Conclusion
No claim is allowed.
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/MCKENZIE A DUNN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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