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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 58-65, 74-75 and 77-81 and species of SEQ ID NO:32 which represents UCH-L1 and a further election of GFAP in SEQ ID NOs: 111 and 112 in the reply filed on 6/3/2024 is acknowledged. While the applicant makes the election with traverse, applicant fails to set forth the reasons for the traverse. Therefore, since no clear reasoning is set forth for the traversal, the restriction is maintained.
The requirement is still deemed proper and is therefore made FINAL.
Newly amended claim 76, previously an independent claim which was withdrawn from consideration, now depends from independent claim 58. Therefore, claim 76 is now under consideration.
Claims 58-65 and 74-81 are under consideration in the instant Office Action.
Priority
Newly amended claim 76, now under consideration, is only present in the instant specification filed on 10/30/22. Claim 76 requires deiminase inhibitors selected from a large genera of possible inhibitors was not disclosed in the provisional or PCT/US2019/029856. Therefore, this claim only has priority to the instant specification filed on 10/30/2020.
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.
Claims 58-65, 74-81 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.
See MPEP § 2173.05(s) which states: “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
In the instant claims, there are incorporation of by reference of Tables 1, 2, and 3 in claims 58, 62, 74-75, 77-80. These claims are indefinite since they may be identified by sequence identifiers which is a practical way of identifying peptides, proteins and antibodies. Therefore, all claims that depend from these independent claims are also found indefinite.
Response to Arguments
Applicant's arguments filed 7/23/2025 have been fully considered but they are not persuasive. Applicant argues that “specific figure or table "is permitted ... where it is more concise to incorporate by reference than duplicating a drawing or table into the claim."” Applicant argues that since their proteins are modified and would span many pages that there Tables are more concise. This is not found persuasive because the information in these tables are proteins and have sequence identifiers associated with them. Therefore, listing these sequence identifiers for each protein is the appropriate and concise way of presenting them in the instant claims. Therefore, appropriate correction is required.
Claim Rejections - 35 USC § 112
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 61, 74-75 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.
Claim 61 and 74-75 are drawn to a diagnostic device that comprises a plurality of deiminated capture peptides, wherein the plurality of deiminated capture peptides comprises at least one deiminated capture peptide for each target deiminated variant that comprises at least a deiminated portion of the target deiminated variant. As such, the claims are directed to a device comprising the use of a genus of deiminated capture peptides defined entirely by function.
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 drawn to a method of capturing autoantibodies against deiminated capture peptides to diagnose ODBI or ODCI subjects, wherein the method uses a device with deiminated capture peptides. The specification, however, does not set forth a structure for the device comprising a plurality of deiminated capture peptides.
The 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 USPQ2dat1966.
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).
Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). See MPEP 2163.02.
The specification defines the device as a device with a plurality of deiminated capture peptides to detect antibody levels. The definition of the device in the instant specification at [00110] only describes the function and fails to set forth any specific structure for device itself. Due to the failure of the disclosure setting forth any structure except the intended use of detecting auto antibodies in a sample and specific deiminated capture peptides, there is no guidance on what is the device is. The device reads on anything such as a glass slide, a flow strip assay or a machine requiring a computer to make an analysis that is specific for a diagnosis. This description of the device offers no distinguishing characteristics from that taught by the prior art. Therefore, it is unclear what is encompassed by this term in the instant specification and claims and no written description support for any specific device as being claimed in the instant application. The new functional property that was not identified in the prior art must be described in detail so that one would understand how it is distinguished from all the possible devices already described in the prior art.
The specification must set forth the precise invention for which a patent is solicited, in such manner as to distinguish it from other invention and from what is old. It must describe completely a specific embodiment of the process, machine, manufacture, composition of matter or improvement invented, and must explain the model of operation or principle wherever applicable. The best most contemplated by the inventor of carrying out this invention must be set forth. 36 C.F.R. 1.71.
Therefore, claims 61, 74-75 do not meet the written description requirement.
Response to Arguments
Applicant's arguments filed 7/23/2025 have been fully considered but they are not persuasive. Applicant argues that “the specification discloses numerous species representative of the claimed genus of deiminated capture peptides, e.g., deiminated capture peptides useful for detecting antibodies specific to a target deiminated variant of a target protein listed in Table 1 or a fragment thereof, a target protein listed in Table 2 or a fragment thereof, or a target protein listed in Table 3 or a fragment thereof, e.g., the peptide sequences set forth in Table 1 and SEQ ID NOs 35-91, the peptide sequences set forth in Table 2 and SEQ ID NOs 92-130, and the peptide sequences set forth in Table 3 and SEQ ID NOs 131-142, respectively”. This argument is not on point since the written description is towards a device that requires these target deiminated variants. While the applicant does have support for specific deiminated proteins set forth in the instant specification, they do not have support for ay device that requires these proteins. There is no evidence that the applicant has a ”device” with the required specifics and therefore, their arguments are not found persuasive.
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 58-65, 74-81 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claims recite a method of detecting, therefore diagnosing, oxygen-deprivation brain injury (ODBI) or oxygen-deprivation causing injury (ODCI) in a subject suspected of or at risk of having ODBI or ODCI by measuring the levels of specific autoantibodies. This judicial exception is not integrated into a practical application because method relies on the detection of the levels of naturally occurring autoantibodies against deiminated proteins to determine whether the subject is suffering from an oxygen-deprivation brain injury (ODBI) or oxygen-deprivation causing injury (ODCI). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they rely on using the levels of naturally occurring autoantibodies to observe a diagnosis of oxygen-deprivation brain injury (ODBI) or oxygen-deprivation causing injury (ODCI). The new claim 76, now under consideration, is depended upon the method solely directed to performing the steps to determine the natural correlation in the patient population and then to “apply it.” Moreover, a claimed treatment step or agent must be “particular”, i.e., specifically identified, so that it does not encompass all applications of a judicial exception(s) in order to integrate it into a practical application. The instant treatment limitation is not considered a “particular” treatment and is instead considered merely instructions to apply the judicial exception or is merely indicating a field of use. See MPEP § 2106.05(h).
The subject matter eligibility under 35 U.S.C. 101 of natural products (i.e., whether the claimed product is a non-naturally occurring product of human ingenuity that is markedly different from naturally occurring products) was confirmed by the U.S. Supreme Court decisions including Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. _, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013), and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101 USPQ2d 1961 (2012). "[L]aws of nature, natural phenomena, and abstract ideas" are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. __, __ (2010) (slip op., at 5). "Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work." Gottschalkv. Benson, 409 U. S. 63, 67 (1972).
In Prometheus, the Court found that "[i]f a law of nature is not patentable, neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Additionally, "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law". Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at __ (slip op., at 14) ("[T]he prohibition against patenting abstract ideas 'cannot be circumvented by’..., adding 'insignificant post-solution activity'" (quoting Diehr, supra, at 191-192)).
The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any 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 their parts taken separately."
Thus, if the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
In the instant case, based upon an analysis with respect to the claim as a whole, claims 58-65, 74-81 are determined to be directed to judicial exception without significantly more. The rationale for this determination is explained below in view of controlling legal precedent set forth in 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
The instant claims 58-65, 74-81 encompass a process. (Step 1: Yes).
Next, Step 2, is the two-part analysis from Alice Corp. (also called the Mayo test) to determine whether the claim is directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions). (In Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) the Supreme Court sets forth a two-step test for determining patent eligibility. First, determine if the claims encompass a judicial exception (a natural phenomenon/law of nature/abstract idea). If so, then ask whether the remaining elements/steps, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to ‘“transform the nature of the claim’ into a patent-eligible application.” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility. Id. at 2355. In the recent Myriad v Ambry case, the CAFC found claims (drawn to methods comprising obtaining tissue samples, analyzing sequences of cDNA and comparing germline sequences of a gene to wild-type sequences) to encompass the abstract mental processes of ‘comparing’ and ‘analyzing’. Recitation of specific techniques (in Myriad claims 7 and 8 further recited hybridization and PCR) were deemed not “enough” to make the claims patent-eligible since the claims contained no otherwise new process. The elements/steps recited in addition to the judicial exception did nothing more than spell out what practitioners already knew). The instant claims encompass the determination of the levels of autoantibodies against deiminated proteins that are indicative of ODBI or ODCI in subject suspected of, or at risk of ODBI or ODCI, the process that is governed by a law of nature, and thus is a judicial exception. While newly amended claim 58 no longer explicitly call for a diagnosis it still reads on a diagnostic method since it requires the samples from subjects suspected of, or at risk of ODBI or ODCI. Thus, the relation between the autoantibodies against deiminated proteins that are indicative of ODBI or ODCI exists in principle and is a consequence of the ways these factors are metabolized by the body, entirely natural process, a natural phenomenon, and thus a judicial exception (Step 2A/1: Yes). Next, prong two of Step 2A requires identifying whether there are additional elements recited in the claim beyond the judicial exception(s) and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. “Integration in to a practical application” requires an additional element or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such as the claim is more than a drafting effort designed to monopolize the exception. In the instant case, the independent claims do not recite any additional elements to integrate the judicial exception into a practical application because all the steps of the claimed methods are limited to only those that measure naturally occurring autoantibodies against deiminated proteins that are indicative of ODBI or ODCI. Newly amended claim 76, now under consideration sets forth the step of “treat it” or “apply it” since it call for a generic type of treatment to be pulled from a wide range of possible genera of treatments without any guidance of when and how to apply in view of the autoantibodies that are detected in the instant method that requires the natural correlation. (Step 2A/2: No). The second step is determining if the claims recite or involve judicial exceptions, such as laws of nature, natural phenomena, or natural products. In this case, the claims involve a natural correlation: autoantibodies against deiminated proteins that are indicative of ODBI or ODCI which is based on a natural correlation. In the next step, it must be determined if the claim as a whole amounts to something significantly more than the judicial exception. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Claims 58-65, 74-81 fail to include any limitations which would distinguish the method because they do not recite any elements, or combinations of elements to ensure that the claim as a whole amounts to significantly more than the judicial exception because the active steps of the claims – collecting biological samples and contacting the samples with deiminated proteins and determining the difference in the levels of naturally occurring autoantibodies − represent routine steps that are recited at a high level of generality and encompass well-understood and purely conventional routine techniques in the art, as shown by the prior art which show that the methods of monitoring pain responses are well known in the art. The instant claims only require the naturally occurring correlation to be observed by applying the known methods in the art. Newly amended claim 76, now under consideration, sets forth the step of “treat it” or “apply it” since it call for a generic type of treatment to be pulled from a wide range of possible genera of treatments without any guidance of when and how to apply in view of the autoantibodies that are detected in the instant method that requires the natural correlation. For example, prior art shows that the methods of using assay to capture autoantibodies of biomarkers that indicate neuronal injury including traumatic brain injury, stroke, etc. as required in the instant claims was known in the prior art as evidenced by Svetlov et al., US2015/0268252 (4/25/2025 PTO-892) and Mueller WO2016/205730 (IDS 10/14/2024). The instantly rejected claims do not recite any elements in addition to the natural correlation that impose meaningful limits on the claim scope and would substantially foreclose others from using this natural correlation of the autoantibodies against deiminated proteins that are indicative of ODBI or ODCI without significantly more. The intended use of this method does not further limit or apply any significant action once the natural correlation has been observed using the claimed method. The natural correlation is found in nature whether it is observed or not and would be present and act quite independently of any effort of the patentee.
Note that the specific deiminated proteins that are indicative of ODBI or ODCI do not add significantly more to satisfy step 2B (Step 2B: No).
Thus, for reasons fully explained above, claims 58-65, 74-81 do not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
Response to Arguments
Applicant's arguments filed 7/23/2025 have been fully considered but they are not persuasive. A natural correlation is something that takes place whether it is being observed or not and it does not matter whether it is disclosed or known in the prior art. It was pointed out in the rejection above that while the correlation of the specifically claimed deiminated proteins that are indicative of ODBI or ODCI may have not been known, instantly claimed active steps used by the applicant to observe the natural correlation are routine and conventional as evidenced by the prior art, as discussed above. The active steps are only data gathering steps that are already described in the prior art and the new improvement that the applicant is claiming is the descriptive natural correlation, the specific biomarkers in the instant claims. The references are provided to show the relevant §101 consideration, given knowledge of the natural correlation (the specific deiminated proteins in this case) the claim does no more than require "detection" by any means, which is clearly directed to "mere data gathering" by routine methods, as evidenced by the references. There are no limitations that are “significantly more” beyond the natural correlation and the routine and conventional methods of data gathering. Further, the new claim 76, now under consideration, is depended upon the method solely directed to performing the steps to determine the natural correlation in the patient population and then to “apply it.” Moreover, a claimed treatment step or agent must be “particular”, i.e., specifically identified, so that it does not encompass all applications of a judicial exception(s) in order to integrate it into a practical application. The instant treatment limitation is not considered a “particular” treatment and is instead considered merely instructions to apply the judicial exception or is merely indicating a field of use. See MPEP § 2106.05(h).
Applicant argues that the provided evidentiary references are not applicable because they only encompass parts of the instant invention. This argument is not on point and is not found persuasive because the references, for this instant rejection, are not intended to teach the instant invention but rather highlight the fact that the active steps, disclosed by evidentiary references, are routine and conventional in the art and known and practiced.
Applicant continues to argue that their claims fit the fact pattern of the Example 29, Diagnosing and Treating Julitis, Claim 1 in the Subject Matter Eligibility Examples: Life Sciences provide on May 2016 and therefore, their claims are eligible as is Claim 1 of the example. Applicant is incorrect in comparing their claims to the Claim 1 of the Julitis example because the instant claims call out a specific correlation of deiminated proteins that are indicative of ODBI or ODCI. While the newly amended claim 58 does not specifically calla for a method of diagnosis, it still reads on a diagnostic method since the claim requires a biological sample taken from a subject suspected of or at risk of having ODBI or ODCI based on what the deiminated proteins detect autoantibodies.
Applicant argues that the claims are eligible since their preamble is a method for detecting antibody levels in a human subject and is not a diagnostic method. Applicant argues that these claims mimic the Julitis claim 1 because it is for a method of antibody expression levels in a human subject and does not require a diagnosis (the judicial exception). This is not found persuasive because while the preamble no longer calls for a diagnosis it still does not mimic the claim 1 example:
The Julitis claim 1, see below:
“1. A method of detecting JUL-1 in a patient, said method comprising:
a. obtaining a plasma sample from a human patient; and
b. detecting whether JUL-1 is present in the plasma sample by contacting the plasma sample with an anti-JUL-1 antibody and detecting binding between JUL-1 and the antibody.”
This example only calls for obtaining a sample and detecting the presence of JUL-1, while the instant claims call for the extra step of determining the expression levels of the autoantibodies and determining if there is a difference, including an increase and decrease, between the controls which are not ODBI or ODCI patients and subject samples. Therefore, the claims still are still ineligible because their method still requires a natural correlation to produce their results, even if not explicitly called a diagnosis.
The claim amendments of claim 76 for a method for treatment of ODBI or ODCI wherein the applicant now claims “and treating the human subject based on detecting a the antibody levels does not add significantly more to the judicial exception because it just reads as “apply it” without any particular limitation of treatment. Appellant argues that all their claims now confer with the 2019 Revised Patent Subject Matter Eligibility Guidance. However, the treatment limitation of the claimed invention must be “particular”, i.e., specifically identified so that it does not encompass all applications of the judicial exceptions, yet the examiner could not find a specific treatment supported by the instant disclosure and none was present in the instant claims. This step is not particular and is instead merely an instruction to “apply” the judicial exception of the instant claims in a generic way. Thus, the treating step does not integrate the judicial exceptions into a practical application nor does it provide significantly more (see e. MPEP 2106.05(a), and 2106.05(f)).
The fact pattern of the Example 29, Diagnosing and Treating Julitis, Claims 5 and 6 in the Subject Matter Eligibility Examples: Life Sciences provide on May 2016 are the best example of a practical application of a natural correlation. In Example 29, Diagnosing and Treating Julitis, Claims 5 and 6 both use a natural correlation for specific practical application. The Julitis claim 5 and 6 require specific treatments after a specific diagnosis. When the additional elements are viewed as a combination, however, the additional elements amount to a claim as a whole that adds meaningful limits on the use of the exception (the correlation and critical thinking step). The totality of these steps including the recitation of a particular treatment (administration of an effective amount of anti-TNF antibodies) integrate the exception into the diagnostic and treatment process, and amount to more than merely diagnosing a patient with Julitis and instructing a doctor to generically “treat the patient”. Further, the combination of steps, which is not routine and conventional, ensures that patients who have Julitis will be accurately diagnosed (due to the detection of JUL-1 in their plasma) and properly treated with anti-TNF antibodies, as opposed to being misdiagnosed as having rosacea as was previously commonplace. See Diamond v. Diehr, 450 U.S. 175, 188 (1981) (“a new combination of steps in a process may be patentable even though all the constituents of the combination were well known and in common use before the combination was made”). Thus, the administration of anti-TNF antibodies, when considered as a combination with the other additional elements, yields a claim as a whole that amounts to significantly more than the exception itself. In contrast, instant independent claim 58 only recites the natural correlation while the dependent claim 76 sets forth a generic groups of treatments to select from to treat the disease/injury. Therefore, the instant claims do not meet the required elements to overcome the judicial exception rejection as argued by applicant.
Therefore, the claims are rejected as being 101 ineligible.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The 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.
Claims 58-65, 74-81 are rejected under 35 U.S.C. 103 as being unpatentable over Svetlov et al., US2015/0268252 (4/25/2025 PTO-892) and Mueller WO2016/205730 (IDS 10/14/2024).
The instant claims recite a method of diagnosing oxygen-deprivation brain injury (ODBI) or oxygen-deprivation causing injury (ODCI) in a subject suspected of or at risk of having ODBI or ODCI by analyzing a biological sample from a subject to detect antibodies (autoantibodies) that bind to deiminated proteins which include proteins such as UCHL1, MAP tau, neurofilament light chain and spectrin beta chain (Table 1); fructose biphosphate aldolase C (ALDOC), glial fibrillary acidic protein (GFAP), enolase (Table 2) and glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) (Table 3). It is noted that oxygen-deprivation brain injury (ODBI) encompasses hypoxia as disclosed in the instant specification [063] and oxygen-deprivation causing injury (ODCI) encompasses traumatic brain injury (TBI) and stroke as disclosed in the instant specification [064].
Svetlov teaches quantitative assay methods to diagnose neurological conditions using the autoantibodies biomarkers (see abstract and [0002], [0011], [0080], [0091]). Svetlov teaches using the detection of autoantibodies against GFAP and other biomarkers to be able to make a diagnosis to determine if a subject suffers from traumatic brain injury, stroke and hypoxia (see [003-007], [0074-0076]) as in instant claim 58. Svetlov teaches using samples from cerebrospinal fluid, blood or plasma to detect the claimed biomarkers (see [004], [0013-0023]) as in instant claims 64-65. Svetlov teaches using proteins that include SBDP20 (see [0019]) and meets the limitation of instant claim 63 which requires 3 to 25 amino acid residues. Svetlov teaches obtaining biological samples from the same subject at different times and control samples and samples between control, mild and moderate TBI (see [0024-0028]) as required in instant claims 59-60. Svetlov teaches using an in vitro device for detecting neuronal injury in a subject by providing a first biological sample into the sample chamber and the device determines the amount of the biomarkers and making the correlation between the levels and the determination of the neuronal injury (see [0010]) as required in instant claims 61 and 75. Svetlov teaches using any number biomarkers up to 10 or more biomarkers using them simultaneously or sequentially to determine the neurological condition of the subject to detect the autoantibodies (see [0085]) as required in instant claim 81. Svetlov teaches biomarkers for the use in diagnosing neuronal injury wherein the biomarkers include MAP, Neurofilament light peptide (NF-L), UCHL1, GFAP, MBP, gamma enolase (NSE), and beta spectrin (see Tables 1-3, pages 5-7) which encompass the biomarkers found in the Tables 1-3 of the instant claims 58, 62, 74 and 77-80. Svetlov teaches that their Table 2 which includes GFAP, UCHL1, NF-L, and NSE produce autoantibodies following the onset of neurological condition. While Svetlov teaches the proteins that would detect the autoantibody biomarkers, Svetlov fails to teach the deiminated version of these proteins.
Mueller teaches using methods for diagnosing TBI in a subject by determining the citrullination levels of one or more biomarkers wherein the increase in citrullination is indicative of subject with TBI (see abstract). One of ordinary skill in the art is aware the protein carbonylation and citrullination is the same as deiminated proteins as in the instant claims. Mueller teaches analyzing at least two biological samples from the subject at different time points to determine citrullination levels (see [0005]). Mueller teaches that the citrullination of proteins ALDOA, ALDOC, GFAP, ENOA (alpha enolase) and MBP (see [0036], [0056]) and meets the requirements of the deiminated protein variants in the instant Tables 2-3 of claims 58, 62, 74 and 77-80. Mueller teaches that the TBI includes ischemia and hypoxia (see {0040]) as required in instant claim 58. Mueller teaches treating TBI with ionomycin which comes from streptomyces conglobatus (see [00115]) and read on analogs and derivates of streptomycin as required in instant claim 76. Mueller teaches that citrullination proteins prompt an autoimmune response due to the formation of antigenic epitopes including in TBI (see [0047-0050] and [0053-0054]) but Mueller fails to teach using these citrullination proteins (deiminated proteins) as biomarker targets to determine the levels of autoantibodies against citrullination proteins (deiminated proteins).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Svetlov and Mueller. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because Svetlov teaches that the level of autoantibodies against specific biomarker proteins are a proven way of diagnosing subjects with neuronal injuries sustained with TBI, stroke and hypoxia injuries. One of ordinary skill would be motivated to use these same proteins, taught by Svetlov and Mueller and use the citrullination proteins (deiminated proteins) to see if these same proteins have induced autoantibodies against the deiminated proteins. Mueller already teaches that there is citrullination of proteins ALDOA, ALDOC, GFAP, ENOA (alpha enolase) and MBP (see [0036], [0056]) with TBI injury and that there are teachings that these proteins produce autoantibodies. Therefore, one of ordinary skill in the art would be motivated to try these citrullination proteins (deiminated proteins) to detect these autoantibodies in a possible TBI subject. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Response to Arguments
Applicant's arguments filed 7/23/2025 have been fully considered but they are not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant argues that Svetlov does not teach claimed proteins in their Tables 1-3 because they are not taught as deiminated proteins. This is not found persuasive because the Svetlov reference is not an anticipatory reference but rather as a teaching that is obvious in combination with another reference, specifically Mueller, to make the claimed invention obvious over the prior art. The fact that Svetlov does not teach the required element of deiminated protein versions but does not detract from the fact that it provides guidance to one of ordinary skill in the art what would be obvious in view of the teachings of the prior art, as evidenced above in the 103 rejection. Svetlov teaches biomarkers for the use in diagnosing neuronal injury wherein the biomarkers include MAP, Neurofilament light peptide (NF-L), UCHL1, GFAP, MBP, gamma enolase (NSE), and beta spectrin (see Tables 1-3, pages 5-7) which encompass the biomarkers found in the Tables 1-3. Applicant further argues that “Mueller does not even disclose deiminated variants of any of the proteins listed in Table 1”. While Mueller does not teach any of the proteins in Table 1, Mueller does teach the proteins that are found in Tables 2-3 but this is make up by Svetlov’s teachings. Mueller teaches analyzing at least two biological samples from the subject at different time points to determine citrullination and that the citrullination proteins include ALDOA, ALDOC, GFAP, ENOA (alpha enolase) and MBP (see [0036], [0056]) which are protein found in Tables 2-3. Therefore, it is the combination of these two references that make the instant claims obvious and applicants arguments are not found persuasive.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675