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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Reopening of Prosecution
In view of the Applicant’s Argument and Response filed on 12/05/2025, PROSECUTION IS HEREBY REOPENED. New grounds of rejection set forth below.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
Priority
This application is a U.S. application filed on 08/10/2022 which claims priority to U.S. Foreign Application No. EP21190690.4 filed on 08/10/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
Claims 1-20 are pending. Claims 2-3 and 12-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim as noted in the Office action of 03/12/2025. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/23/2024. Claims 4-11 are original.
Thus, claims 1 and 4-11 are under examination.
Withdrawn Rejections
The previous rejection of claims 1, 5-6, 9-10 under 35 U.S.C. 102(a)(1), as being anticipated by Landa et al. (Ann Neurol 2021;90:101–117), is withdrawn in light of the Declaration under 37 CFR 1.130 filed 12/05/2025.
Claim Interpretation
The examiner is providing an explanation for the acronyms GluK1, GluK2, GluK3, GluK4 and GluK5 of claim 1 as described by Shalaby et al. (Kainate Receptors Trafficking, Signalling and Functional Roles, Neuroreceptor Endocytosis and Signaling in Health and Disease, Springer Nature Switzerland AG 2025, Chapter 9, First Online: 27 April 2025, pp 195–221). Kainate receptors (KAR) are a subclass of Ionotropic glutamate receptors and are divided into primary and secondary subunits. The primary subunits of kainate receptors are GluK1 (GluR5), Gluk2 (GluR6) and Gluk3 (GluR7). The secondary subunits are Gluk4 (KA1) and GluK5 (KA2). Kainate receptors are known to form homodimers and heterodimers, and they control ion flow in different tissues such as in central nervous system (CNS).
New Objections and Rejections
Claim 1 is objected to because of the following informalities: The claim recites “A method of detection” in the preamble of the claim without specifying what type of a detection method is the claim about (i.e., detect an autoantibody). Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 1 and 4-11 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 claims contain 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.
The claims are drawn to detecting autoantibodies. The analytes to which the antibodies bind to are already drawn to vastly diverse protein species that have different combinations, e.g., heterotetrameric or homotetrameric channels. And the proteins and the detected autoantibodies are involved in different diseases. The claims do not provide any information about the structure of the proteins to which the antibodies bind to. Thus, the claims encompass the detection of autoantibodies to widely varying species. Consequently, the claims are drawn to a widely diverse scope of antibodies.
No particular binding reagents are specifically claimed. Claim 1 requires detecting in a sample an autoantibody binding to Gluk1, Gluk2, Gluk3, Gluk4, and Gluk5 by any possible method with any possible measurement reagent.
The claims comprise the method of detecting autoantibodies specific to immobilized analytes of GluK1, GluK2, GluK3, GluK4, GluK5 or a variant. The specification does not describe a common structure or function among the widely varying species such that its function could be correlated to specific structure by the binding of the autoantibodies. Moreover, variants describe a source but do not provide the structure of the ending product to be used.
The level of knowledge and skill in the art does not allow those skilled in the art to structurally envisage or recognize those binding species to which autoantibodies bind and that would meet the claim limitations. The specification does not describe any physical or chemical properties of the species to which the autoantibodies are expected to bind and that would be expected to be shared by members of the claimed genus. The level of knowledge and skill in the art does not allow those skilled in the art to structurally envisage or recognize which protein species, to which an autoantibody binds to, would meet both the structural and functional limitations of the broad claims.
It is known that these proteins themselves are widely varying in function and structure and
tend to have different protein sequences and binding affinities to antibodies with unpredictable functions. Because the structure of the species within the claimed genus would be expected to vary unpredictably from the structure of the single, described subgenus, the specification has not shown a “representative number” of species within the claimed genus.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement.
Here, the specification has not described a reasonable number of widely varying species that have the function of being capable of binding to autoantibodies, i.e., the required starting materials for the claim, but rather has presented the public with an idea of how to perform an assay that might identify some of the widely varying species that fall within the scope of the claim. Of course, depending on what autoantibodies are screened for in the detection assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face. Because claim 1 (the broadest claim) of the instant application recites a method of detection that comprise widely varying species that are capable of binding to any autoantibody that is qualified by the claim, and the specification only provides evidence that these widely varying species can perhaps bind autoantibodies, the specification does not disclose a structure/function correlation. Furthermore, the specification provides examples and methods for identifying GluK2 autoantibodies from a patient but does not provide examples for identifying other autoantibodies (i.e., GluK1, GluK3, GluK4 and GluK5) (Page 55, “Identification of GluK2 as the main target antigen”; page 56, lines 14, “The specificity of GluK2 antibody reactivity was confirmed by CBA”; page 56, line 23, “Detection of GluK2-abs in other anti-glutamate receptor encephalitis”; page 58, lines 35-38, “We found that glutamate kainate receptors containing GluK2 (previously known as GluR6) are the target of antibodies in some patients with encephalitis or cerebellitis of unclear etiology, and that these antibodies are likely pathogenic”). Thus, there is a lack of reasonable correlation between the narrow disclosure in the specification and the overly board scope of protection sought in the claims of the instant application.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for
lack of written description support, especially in technology fields that are highly unpredictable,
where it is difficult to establish a correlation between structure and function for the whole genus or
to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of widely varying species that would meet the limitations of the claims of the instant application.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states 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).
In the instant case, the skilled artisan cannot envision any structure function correlation for the widely varying species having the function required by the claim, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The protein species, to which an autoantibody binds, is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Therefore, claims 1 and 4-11 of the instant application do not meet the written description requirement.
Claim Rejections - 35 USC § 112(b)
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.
Claim 7 is 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.
Regarding claim 7, the claim recites "wherein the cancer is selected from the group consisting of ...graft versus host disease...". Graft versus host disease is by its very nature not a cancer. Thus, it is not clear how the cancer in claim 7 can actually be "graft versus host disease".
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 and 8-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gahring et al. (Molecular Medicine, Volume 1, Number 3, March 1995, 245-253).
Regarding claims 1 and 5-6, Gahring teaches detecting autoantibodies to the non-NMDA glutamate receptors by analyzing the serum from seven patients with well characterized paraneoplastic neurological syndromes (PNS) (Abstract, Background, Materials and Methods). Gahring teaches the presence of autoantibodies to GluR5 (GluK1 of instant application) receptors (Abstract, Results).
Regarding claims 4 and 11, Gahring teaches using fusion proteins immobilized on test strips to which the patient’s serum is tested for to detect autoantibodies (Page 248, right column, second paragraph).
Regarding claim 8, Gahring teaches using fusion protein of GluR5 for example to detect autoantibodies (Page 248, right column, second paragraph).
Regarding claim 9, Gahring teaches detecting autoantibodies with immunoassays such as western blot, immunohistochemistry, and immunocytochemistry (Abstract, Materials and Methods).
Regarding claim 10, Gahring teaches detecting the autoantibodies from serum (Abstract, Results).
Response to Arguments
Applicant’s arguments with respect to claims 1 and 4-11 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed.
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/OMAR RAMADAN/Examiner, Art Unit 1678