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 without traverse of Group I, claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 and declared species in the reply filed on 9/22/2025 is acknowledged. Upon further consideration the species requirements for Group I invention are no longer required.
Claims 20-21, 23, 27, 29, 31, 34, 54-55, 57, 61, 63, 65, 68 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/22/2025.
Claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 are under consideration in the instant Office Action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 1-2 and 35-36 are objected to because of the following informalities: the claims contain multiple periods within each claim. For example, "a.". Please change format to "a)". Further, extra numbers within the claims that may be confused with claim numbers, for example; “1. the subject’s level…”, used to list steps as in instant claim 1 also needs to be modified to “i) the subject’s level…”. Applicant's attention is directed to MPEP 608.01(m) that deals with claim format. In particular, MPEP 608.01(m) discloses that each claim begins with a capital letter and ends with a period. In addition, it is disclosed that periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995). Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). Appropriate correction is required.
Note that cancelled claim 13 has it identifier “Cancelled” struct out. Appropriate correction is required.
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 14 and 48 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.
Claims 14 and 48 recites the limitation "the amount". These claims depend from independent claims 1 and 35 which do not mention any amount. There is insufficient antecedent basis for this limitation in the claim.
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 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 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. Method claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53, directed to determining the presence of Traumatic Brain Injury (TBI) in a patient, set forth laws of nature by reciting relationship between changes in the levels of naturally occurring factors and the pathology itself. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for reasons that follow.
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 brief, in Prometheus, a method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder is the focus. This method comprises a) administering 6-thioguanine to patients and b) determining the level of 6-thioguanine in the patients and c) correlate the level of 6-thioguanine, i.e. a certain level/red blood cells, with the decision whether a need for increase or decrease the amount of 6-thioguanine treatment in said patients.
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 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 are determined to be directed to a judicial exception without significantly more. The rationale for this determination is explained below in view of controlling legal precedent set forth in 2014 Interim Guidance on Patent Subject Matter Eligibility (79 FR 74618) dated December 16, 2014 and 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
The instant claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 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 1-4, 6, 8, 12, 14, 16, 19, 35, 38, 40, 42, 46, 48, 50 and 53 encompass changes in the levels of GFAP and UCH-L1 during pathology of TBI, the process that is governed by a law of nature, and thus is a judicial exception. The GFAP and UCH-L1 are all naturally occurring factors that are expressed differently during pathology of TBI apart from any human action. The relation between the levels of expression of these factors and pathology of TBI 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 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 factors during a naturally occurring pathology. 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 protein in TBI. Claims 4 and 38 sets forth the step of “treat it” or “apply it” since it call for “treating the subject for a mild, moderate, moderate to severe, or severe TBI when the subject's levels of GFAP and UCH-L1are elevated” which is a generic statement of treatment without any guidance of what treatment to use in view of the levels that are detected in the instant method that requires the natural correlation (Step 2A/2: No).
Finally, claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 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— performing an assay to measure a level of a protein—represent routine steps that are recited at a high level of generality and encompass well-understood and purely conventional routine techniques in the art (see claims 2, 12, 36 and 46, for example, reciting representative well-known assays and CT and MRI scans). The claims 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 determining the levels of naturally occurring proteins − 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 TBI 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. For example, prior art shows that the methods of using assay to measure GFAP and UCH-L1 that indicate neuronal injury including traumatic brain injury required in the instant claims was known in the prior art as evidenced by McQuiston et al., US 20190376983 (IDS 6/5/25), McQuiston et al., US 20180306812 (instant PTO-892) and McQuiston et al., US 20180364261 (instant PTO-892). 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 GFAP and UCH-L1 that are indicative TBI 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. (Step 2B: No).
Thus, for reasons fully explained above, claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 do not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
Claim Rejections - 35 USC § 102
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.
Claims 1-4, 6, 8, 12, 16, 19, 35-38, 40, 42, 46, 50 and 53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McQuiston et al., US 2018/0364261 (instant PTO-892).
Claims 1-4, 6, 8, 12, 16, 19, 35-38, 40, 42, 46, 50 and 53 encompass methods of evaluating a subject for head injury by measuring the levels of GFAP and UCH-L1 to determine the presence of TBI. The critical levels are above 30 pg/mL for GFAP and above 360 pg/mL for UCH-L1.
McQuiston teaches of methods that determine the levels of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP), or a combination thereof and whether to perform imaging, such as magnetic resonance imaging (MRI) or computerized tomography (CT) scan on a human subject that has sustained or may have sustained an injury to the head. These methods involve detecting levels and changes in levels of UCH-L1 in samples taken from a human subject at time points within 12 hours (about 12-48 hours as claimed), after the subject has sustained or may have sustained an injury to the head (see abstract, paragraphs 5-6, 16-17, 19, 24-25) and reads on instant claims 1-2 and 35-36. McQuiston teaches that UCH-L1 levels are about 400pg/ml and GFAP levels are about 50pg/ml (see paragraphs 16-17, 30-31) and reads on the levels of instant claims 1-4, 35-38. McQuiston teaches determining mild or moderate or severe TBI in a subject, administering treatment and monitoring the subject (see paragraphs 20, 48-49, 267) and reads on instant claims 4 and 38. McQuiston teaches that the sample can be obtained after the subject sustained a head injury caused by physical shaking, blunt impact by an external mechanical or other force that results in a closed or open head trauma, one or more falls, explosions or blasts or other types of blunt force trauma; after the subject has ingested or been exposed to a chemical, toxin or combination of a chemical and toxin and obtaining the sample from a subject who has an autoimmune disease, brain tumor, or other condition (paragraph 170) and reads on instant claims 8 and 42. McQuiston teaches that the biological sample can be obtained within 10 minutes, 15minutes, 20 minutes, 12hrs and 24hrs after suspected head injury (see paragraphs 212-214) and reads on instant claims 6, 16, 40, and 50. McQuiston teaches using assay to determine the levels of the biomarker using a an immunoassay that used whole blood or serum and a point-of-care device (see paragraph 225) and reads on instant claims 1, 12, 19, 35, 46 and 53
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,849,548, 1-14 of U.S. Patent No. 10,866,251, claims 1-22 of U.S. Patent No. 10,877,048, claims 1-16 of U.S. Patent No. 10,877,038, claims 1-36 of U.S. Patent No. 11,016,105, claims 1-18 of U.S. Patent No. 11,931,161, claims 1-24 of U.S. Patent No. 12,099,069, claims 1-31 of U.S. Patent No. 12,105,098, claims 1-26 of U.S. Patent No. 11,022,617, claims 1-38 of U.S. Patent No. 12,105,100, claims 1-19 of U.S. Patent No. 12,092.647, and claims 1-18 of U.S. Patent No. 12,085,567. Although the claims at issue are not identical, they are not patentably distinct from each other because all the patented claims encompass diagnosis of TBI using the same biomarkers—GFAP and UCH-L1—and recite the same critical levels that stand for TBI. The U.S. Patents listed above all claim a version of: A method comprising: performing at least one assay for UCH-L1 and GFAP, or a combination thereof in at least one sample that is whole blood, serum, plasma, or cerebrospinal fluid obtained from a human subject, wherein the sample is obtained from the subject within about 12 hours of an actual or suspected injury to the head; and i. performing a head computed tomography (CT) scan or MRI on the subject when the level of GFAP is greater than or equal to 30 pg/mL and the level of UCH-L1 is greater than or equal to 360 pg/mL. Although the claims at issue are not identical, they are not patentably distinct from each other because present claims and the patented claims encompass very similar methods, which recite the same steps, use the same materials and accomplish identical results.
Claims 1-4, 6, 8, 12, 14, 16, 19, 35-38, 40, 42, 46, 48, 50 and 53 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7-9, 11-15, 20-24, 26, 28-29, 31 and 33-34 of copending Application No. 17/747,397; claims 1-3, 7, 9, 14-16, 18-34, 38 and 41-60 of copending Application No. 17/839,669; claims 1-24 and 27-32 of copending Application No. 18/474,826; claims 1-19 of copending Application No. 18/509,717; claims 1-17 of copending Application No. 18/443,416; claims 1-2, 10, 12-13, 20, 22-23, 25-29, 32, 34-35, 37 and 40 of copending Application No. 18/792,630; claims 47-64 of copending Application No. 18/795,240; claims 1, 5, 7-10, 12, 14-18, 20, 23-24, 26, 29, 31-32 and 34 of copending Application No. 18/804,253; claims 1-4, 6, 8, 12, 14, 16, 19-21, 23, 27, 29, 31, 34-38, 40, 42, 46, 48, 50, 52-55, 57, 61, 63, 65 and 68 of copending Application No. 18/147,360;. Although the claims at issue are not identical, they are not patentably distinct from each other because Although the claims at issue are not identical, they are not patentably distinct from each other because all the patented claims encompass diagnosis of TBI using the same biomarkers—GFAP and UCH-L1—and recite the same critical levels that stand for TBI wherein one sample that is whole blood, serum, plasma, or cerebrospinal fluid obtained from a human subject, wherein the sample is obtained from the subject within about 12 hours of an actual or suspected injury to the head; and performing a head computed tomography (CT) scan or MRI on the subject when the level of GFAP is greater than or equal to 30 pg/mL and the level of UCH-L1 is greater than or equal to 360 pg/mL. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675