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 .
Election/Restrictions
1. Applicant's election with traverse of Group I in the reply filed on August 25, 2025 is acknowledged. The traversal is on the ground(s) that Groups I and II read on the same inventive concept, pp. 7-8 of the Response. Applicant’s arguments have been found persuasive and Groups I and II have been rejoined.
2. The restriction requirement with respect to Groups III and IV is still deemed proper and is therefore made FINAL.
3. Claims 14, 15 and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention(s), there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on August 25, 2025.
4. Claims 1-13, 16 and 17 are under examination.
Claim Objections
5. Claim 16 is objected to because of the following informalities:
The claim recites “NSAID” without first providing the full name of the term. It is suggested that the term be spelled out at its first use so that it is clearly understood what it stands for. Appropriate correction is suggested.
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.
6. Claims 2, 6, 11-13 and 16 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.
7. Claim 2 is indefinite wherein it recites functional language. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.” In the instant case, the claim recites the method of the base claim 1 but then defines the protein that is essential to practice the method—the guanidinylated YB-1-like cold-shock domain (YB-1-G) forms part of a YB-1 protein—by using a verb “to form,” such as to make, to construct or to create, or in other terms by functional language. While a functional limitation can provide a patentable distinction (limit the claim scope) by imposing limits on the function of a structure, material or action, in the instant case it is unclear what material/structural or manipulative differences are encompassed by a protein that “forms part of a YB-1 protein.” Since the claim fails to meet the criteria set forth in MPEP 2173.05(g), then the claim is rejected as being indefinite. Amending the claim to recite “comprises” or “consists of,” for example, would overcome this ground of rejection.
8. Applicant is advised that one of the purposes of the 112(b), second paragraph is to provide a clear warning to others as to what constitutes infringement of the patent (see, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). The test for definiteness under 35 U.S.C. § 112, second paragraph, is whether “those skilled in the art would understand what is claimed when the claim is read in light of the specification.” Orthokinetics, Inc. v. Safety Travel Chairs, Inc., 806 F .2d 1565 (Fed. Cir. 1986) (citations omitted).
In precedential decision Ex parte Kenichi Miyazaki, Appeal 2007-330, BPAI stated “In particular, rather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amendable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph.”
Further, the federal Circuit stated in Halliburton Energy Servs.:
When a claim limitation is defined in purely functional terms, the task of determining whether that limitation is sufficiently definite is a difficult one that is highly dependent on context (e.g., the disclosure in the specification and the knowledge of a person of ordinary skill in the relevant art area). We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiner demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.
Halliburton Energy Servs. V. M-ILLC 514 F .3d 1244, 1255 (Fed. Cir. 2008) (emphasis added).
9. Claim 6 is vague and indefinite for reasons that follow. First, steps (i) and (ii) appear to be in conflict with each other. Specifically, step (i) indicates detection, such as presence, of YB-1-G as a diagnostic measure for lupus nephritis, wherein step (ii) states that it is an increase in the level of YB-1-G that stands for diagnosis of the disease; thus, effectively excluding the presence of YB-1-G as a diagnostic marker (increase in the levels indicates that the protein of interest is present in control sample). Next, step (ii) comprises steps (a) and (b), each reciting different values and levels of YB-1-G, “the borderline” between the samples and “the total polypeptide content comprised in the respective sample.” It is not clear and cannot be determined from the claim or the specification as filed what defines a level as compared to a value, or a borderline, or what specific polypeptide content is intended by the claim. Moreover, the term “increased” in claim 6 is a relative term which renders the claim indefinite if a point of reference is not clearly recited within the claim. Therefore, recitation of “optionally compared with” renders the claim indefinite. Applicant is advised to rewrite the claim to better express claimed subject matter.
10. Claim 11 recites the limitation "lupus nephritis" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
11. Claim 13 provides for the use of a protein but, since the claim does not set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
12. Claims 12 and 16 are indefinite for being dependent from indefinite claim(s).
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.
13. Claims 1-9, 11-13, 16 and 17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an in vitro method of detecting a protein that comprises YB-1-G, a guanidinylated form of YB-1-like cold-shock domain of YB-1 protein, by mass spectrometry, does not reasonably provide enablement for the full scope of the claimed invention. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Claims 1-9, 11-13, 16 and 17 are directed to methods that require practicing an in vitro assay to detect a guanidinylated form of YB-1-like cold-shock domain of YB-1 protein. Claims 7-9 specifically recite detection by direct or indirect immunodetection and detection of autoantibodies specific for YB-1-G. However, the specification does not provide sufficient guidance to enable practice the full scope of the claimed invention without undue experimentation.
The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
The specification discloses the discovery of an association between guanidinylated YB-1-like cold-shock domain (YB-1-G) of a YB-1 protein and pathology of lupus nephritis in an individuals suffering from systemic lupus erythematosus (SLE). The data presented within the disclosure are limited to measurements using mass spectrometry, see working examples at pp. 39-49. The only antibody specific for YB-1 protein is described at p. 48, anti-human YB-1 C-terminal. There appears no further information of using any antibody or fragment thereof that specifically recognizes YB-1-G, or any data related to detection of autoantibodies to YB-1-G, as currently claimed.
As stated in MPEP 2163(II)(A)(3), a specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) (“[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim.”); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) (“[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose.”); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves).
In the instant case, the instant specification fails to describe, with particularity, any high affinity anti-YB-1-G antibodies that were produced, or autoantibodies that were detected as of the earliest effective filing date of the instant application.
Producing antibodies specifically against guanidinylated proteins (i.e., proteins modified by guanidinylation, a non-enzymatic post-translational modification) is not yet considered a highly routine or standardized practice. The process of generating antibodies in general is considered “routine” as it follows established methodologies and uses well-documented approaches. However, there appears no prior art available at the time of filing that demonstrate availability of antibodies against guanidinylated proteins in particular, or provide sound scientific reasoning to support a conclusion that generating high-affinity antibodies to site-specific post-translationally modified guanidinylated protein requires no undue experimentation.
The nature of the invention places it in the class of invention which the Federal Circuit has characterized as "the unpredictable arts such as chemistry and biology." Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
At p. 16, the specification contemplates detection and identification of YB-1-G “by any means.” It further points out that “[I]dentifying YB-1-G may be direct or indirect” and alludes to using anti-YB-1-G antibodies as well as measuring the levels of autoantibodies to YB-1-G as a measure to detect the levels of YB-1-G. However, the specification fails to teach any factual evidence directly supporting such assertion. There is no teaching how specific post-translationally modified proteins arise in autoimmunity and harnessed for diagnostics, or how to make decisions regarding critical levels specifically indicative of the pathology of lupus nephritis. As such, Applicant has merely provided a starting point for research and experimentation and not a meaningful enabling disclosure of how to practice the full scope of Applicant’s invention as currently claimed.
The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. In the decision of Genentec, Inc, v. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that:
“[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure.” The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art,” “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement.”
The instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed methods without first making a substantial inventive contribution to perfect the method and complete the invention.
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.
14. Claims 6 and 13 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 and use claim(s) 6 and 13 set forth laws of nature by reciting relationship between changes in the levels of naturally occurring factors and the pathology of lupus nephritis. 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). "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., ("[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 6 and 13 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 6 and 13 are directed to a process (encompass a process, interpreting “use” as a process, not a product) (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 6 and 13 encompass changes in the presence or levels of YB-1-G, guanidinylated form of YB-1-like cold-shock domain of YB-1 protein, during pathology of lupus nephritis, the process that is governed by a law of nature, and thus is a judicial exception. The guanidinylated YB-1 is a naturally occurring factor that is expressed differently during pathology of lupus nephritis apart from any human action. The relation between the levels of YB-1-G and pathology of lupus nephritis exists in principle and is a consequence of the ways this factor is 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 a naturally occurring factor during a naturally occurring pathology. (Step 2A/2: No).
Finally, claims 6 and 13 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 samples S, detecting or measuring the amount of YB-1-G—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 representative claims 9 and 10 reciting all known assays and techniques) (Step 2B: No).
Thus, for reasons fully explained above, claims 6 and 13 do not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
15. Claim 13 is further rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Conclusion
16. No claim is allowed.
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/OLGA N CHERNYSHEV/ Primary Examiner, Art Unit 1675
November 12, 2025