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
Applicant’s election of Group I (claims 1-8) in the reply filed on 3/23//2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-8 are under consideration by the Examiner.
Claims 9-27 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Information Disclosure Statement
3. The information disclosure statements (IDS) submitted on 5/15/2023, and 7/11/2023 are in compliance with the provisions of 37 CFR 1.97 and have been considered by the examiner.
Applicant is reminded of their duty to disclose to the Office all information known to the person to be material to patentability as defined in 37 CFR 1.56. As stated therein, “[e]ach individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patentability as defined in this section”.
Claim Objections
Claims 4-8 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only and cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 4-8 have not been further treated on the merits.
Claim Rejections - 35 USC § 101
5. 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.
5a. Claims 1-3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Independent claim 1 is drawn to “a method for assigning a subject having idiopathic multicentric Castleman disease (iMCD) to a group having a higher or lower probability of responding to treatment for iMCD comprising: comparing the amount of CXCL13 in a biological fluid obtained from the subject following commencement of the treatment to the amount of CXCL13 in a biological fluid obtained from the subject prior to commencement of the treatment; and, assigning the subject to a group having a higher probability of responding to the treatment if the amount of CXCL13 in the biological fluid obtained from the subject following commencement of the treatment represents a significant downward deviation relative to the amount of CXCL13 in the biological fluid obtained from the subject prior to commencement of the treatment.”
Dependent claim 2 recites “the method according to claim 1, wherein the biological fluid obtained from the subject following commencement of the treatment was obtained about one week following commencement of the treatment” and dependent claim 3 recites “the method according to claim 1 or claim 2, wherein the treatment comprises anti-IL-6 therapy”.
The broadest reasonable interpretation of these limitations is that it is required that an arithmetic calculation be performed to obtain “a significant downward deviation” relative to the amount of CXCL13 in the biological fluid obtained from the subject prior to commencement of the treatment. These limitations, therefore recite 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, these limitations fall 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, the limitation also falls into the “mental process” groupings of abstract ideas. Accordingly, the limitations “comparing”, “assigning” and “a significant downward deviation” recite 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).
Furthermore, this judicial exception is not integrated into a practical application. Claims 1-3 do not include any additional elements, besides the judicial exception. Therefore, the claims are directed to the judicial exception.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. A claim that focuses on the use of a judicial exception must also include additional elements or steps to show that the inventor has practically applied, or added something significant to, the natural principle itself. See Mayo 101 USPQ2d at 1966. Adding steps to a natural biological process or an abstract idea that only recites well-understood, routine, conventional activity previously engaged in by researchers in the field would not be sufficient. See id. At 1966,1970. As stated in MPEP 2106.05(d), the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. Determining the level of a biomarker, in this case CXCL13, in a biological sample by any means has been determined as one of the well-understood, routine, conventional activities. See Mayo, 566 U.S. at 79,101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017). The claims do not recite a particular assay for processing the sample. Thus, the claims are generic for this step and encompass assays that are routine in the art for quantifying cytokines and a chemokine.
Furthermore, the additional feature of claim 3, “wherein the treatment comprises anti-IL-6 therapy”, does not ensure that the claims amount to significantly more than the natural principle itself because this treatment step is generic and not particular or specific therapy. Since the claims use conventional means to observe a natural correlation and the steps of the claimed method are not sufficient to transform unpatentable natural correlations into patentable applications of those regularities. This is also supported by the findings of the in Ariosa Diagnostics, Inc. v. Sequenom, Inc., 115 USPQ2d 1152 (Fed. Cir. 2015), wherein the Federal Circuit held that claims that measure biological substances using methods that are routine and conventional do not amount to more than reliance on a correlation that is a law of nature for patentability. The additional element of “treatment comprises anti-IL-6 therapy”, is recited at a high level of generality and does not require any particular application of the recited judicial exception. Thus, the additional element of “treatment comprises anti-IL-6 therapy” is at best the equivalent of merely instructions to apply an exception cannot provide an inventive concept. In conclusion, claims 1-3 as recited, do not qualify as patent eligible subject matter under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112(a), lack of written description
6. 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.
6a. Claims 1-3, 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant has claimed:
“a method for assigning a subject having idiopathic multicentric Castleman disease (iMCD) to a group having a higher or lower probability of responding to treatment for iMCD comprising:
comparing the amount of CXCL13 in a biological fluid obtained from the subject following commencement of the treatment to the amount of CXCL13 in a biological fluid obtained from the subject prior to commencement of the treatment; and,
assigning the subject to a group having a higher probability of responding to the treatment if the amount of CXCL13 in the biological fluid obtained from the subject following commencement of the treatment represents a significant downward deviation relative to the amount of CXCL13 in the biological fluid obtained from the subject prior to commencement of the treatment.”
However, there does not appear to be a description of how the CXCL13 is measured or which treatment is administered as recited in claim 1. The method of measuring the amount of CXCL13 as recited in claim 1, does not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph because the claims do not recite how CXCL13 was measured. the specification does not apprise one of ordinary skill in the art with a description of every and all methods for measuring CXCL13 and administering every and all treatments as encompassed by independent claim 1. In other words, the specification provides no nexus between quantifying the CXCL13 levels in a subject sample and correlating the result to the subject having iMCD and responding to a treatment for iMCD. The claims do not provide any threshold or standard upon which the correlation is based, and simply provide for quantifying CXCL13 and making a correlation. Therefore, the specification provides insufficient written description to support the genus encompassed by the claims. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
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 USPQ2d 1966.
A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed method. The claimed method encompasses correlating any measured value of the claimed biomarker CXCL13 with response to a treatment for iMCD in the subject. Therefore, one skilled in the art would require guidance in determining the basis of the correlation between the quantification and the identification of response to treatment of a subject. Therefore, the specification provides insufficient written description to support the genus encompassed by the claims.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., 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 applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: “A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The Court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). Also see Enzo-Biochem v. Gen-Probe 01-1230 (CAFC 2002).
As such, there is no demonstration that the various methods for obtaining the amount of CXCL13 encompassed in the method of independent claim 1 are correlated with the recited response to treatment with a iMCD therapy. Therefore, in view of all of the above, artisans would reasonably conclude that Applicant was not in possession of the invention as presently claimed at the time the instant application was filed.
Claim Rejections - 35 USC § 112(b)
6. 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.
6a. Claims 1-3 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 pre-AIA the applicant regards as the invention.
Claim 1 is rejected as vague and indefinite for several reasons.
Claim 1, line 4, the independent claim of the instant application, is vague and indefinite because it recites a "a biological sample obtained from the subject" and it is unclear what this limitation specifically encompasses. The specification, paragraph [38] recites that the "biological fluid may be whole blood, serum, plasma, or any other fluid derived from the subject in question”. The recitation of “may be” is also exemplary, vague and indefinite. This rejection can only be obviated by reciting the specific biological fluid for which there is a basis in the instant specification.
Claim 1, lines 1-2 and 7, are vague and indefinite for the recitation of “assigning” and “having a higher or lower probability” which limitations are unclear.
Claim 1, lines 2-3, is vague and indefinite because it recites “treatment for iMCD” and it is unclear which “treatment” is being referred to in the claim.
Claim 1, line 9, is vague and indefinite because it recites “significant downward deviation” which is a subjective limitation. It is unclear what the term “significant” encompasses. Is the “significant downward deviation” 5%, 10% or 25%? This rejection can be obviated by reciting the specific deviation for which there is a basis in the instant specification.
Claim 1 is vague and indefinite because it fails to recite how measuring the amount of CXCL13 is achieved.
Claim 2 is rejected as vague and indefinite for several reasons.
Claim 2, line 2, recites the limitation “about one week” and it is unclear if this limitation encompasses 5 days, 10 days or something else.
Claim 2, lines 2-3, is vague and indefinite because it recites “treatment” and it is unclear which “treatment” is being referred to in the claim.
Claim 3, line 2, is vague and indefinite because it recites “treatment comprises anti-IL-6 therapy” and it is unclear which “treatment” is being referred to in the claim.
Claim rejections-35 U.S.C. 102
7. 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.
7a. Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by
Pierson et al. (2018).
Pierson et al disclose a method for assigning a subject having idiopathic multicentric Castleman disease (iMCD) to a group having a higher or lower probability (based on CXCL13 levels) of responding to treatment for iMCD (siltuximab is the monoclonal IL-6 antibody administered for treatment) (See abstract; page 903, columns 1-2). The reference also discloses that seven days after siltuximab was first administered, 9 proteins were significantly different between responders and non-responders: CXCL13 being one of the proteins (page 904, column 1). The reference discloses that CXCL13 was recently discovered as a key cytokine in iMCD, and the early and significant decline of CXCL13 in responders versus non-responders was highly notable (See Figure 2B-2D). Prior to treatment, CXCL13 was significantly higher in this cohort of iMCD patients than in a group of age-matched healthy donors, and by day 64, CXCL13 levels in siltuximab responders decreased to levels approaching the healthy donor range but remained-elevated in non-responders. Therefore, the prior art method discloses all the limitations of the instant claims encompassing assigning a subject having iMCD to a group having a higher or lower probability of responding to iMCD treatment by comparing the amount of CXCL13 in a biological fluid obtained from the subject following commencement of the treatment (with the anti-IL-6 monoclonal antibody siltuximab), to the amount of CXCL13 in a biological fluid obtained from the subject prior to commencement of the treatment, and the biological fluid obtained from the subject following commencement of the treatment was obtained about one week following commencement of the treatment with siltuximab (page 904, columns 1-2).
Therefore, the reference anticipates claims 1-3.
Conclusion
No claim is allowed.
Claims 1-3, are rejected.
Claims 4-8 are objected.
Advisory Information
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/PREMA M MERTZ/ Primary Examiner, Art Unit 1674
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