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 .
Interview Summary
The Examiner acknowledges the interview summary submitted 03/09/26 concerning a discussion with the Applicant on 03/03/26. During the discussion the Examiner proposed to limit claims 1 and 11 to only the 1-1059 sequence and to provide the appropriate Sequence identifier and to cancel claims 13-17. The Examiner did not propose to amend the claims to recite amino acids of a SEQ ID NO: No agreement was reached and the Applicant ask the Examiner to proceed with an office action. Upon review the current claims utilize open language and allow for the full length of nephrin and also allows for antigens having amino acids of SEQ ID NO: 1. Therefore, the following rejections have been made.
Status of the claims
The amendment filed 12/18/25 and the supplemental amendment filed 03/09/26 is acknowledged and has been entered. Claims 1-4, 6, 10-11, 13-14 and 16 were amended in the amendment filed 12/18/25. Claim 15 was canceled and new claim 17 was added in the amendment filed 12/18/25. Claims 1 and 11 were amended in the supplemental amendment filed 03/06/26. Accordingly, claims 1-14 and 16-17 are pending and under examination.
Withdrawn Rejections
All rejections of claims not reiterated herein, have been withdrawn.
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 1-3, 11-14 and 16-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and/or to laws of nature/natural phenomena without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
The claims are directed to a naturally occurring correlation between the levels of anti-nephrin antibodies in a subject at risk of MCD or having MCD or an acute acquired nephrotic syndrome or focal segmental glomerulosclerosis (FSFS) compared to a reference level and eligibility of a subject who has end stage renal disease for kidney transplant. Claims 11-12 and 17 also describes an abstract idea, law of nature, or natural phenomenon in claim by requiring a sample from a subject who has, or who is suspected of having the recited conditions and testing for levels of the recited antibodies in these subjects.. The claims are directed to a naturally occurring correlation between the levels of the recited biomarkers in a subject with MCD, acute acquired nephrotic syndrome or FSGS and comparing to a reference to provide the level to a healthcare provider as recited in claim 12.
Step 2A, Prong 2
The additional elements of providing a sample from a subject and detecting a level of anti-nephrin antibodies in the sample and making a comparison to a reference level wherein detection is with a recombinant nephrin comprising SEQ ID NO:1, western blot, ELISA, protein, array radio-immunoassay (as recited in claim 17) does not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Also, with respect to the recitations “identifying a subject who has a level of anti-nephrin antibodies in the sample above a reference level ….” (as recited in claims 1 and 13). The “identifying” statement at best articulates the judicial exception, amounting only to a general instruction to apply or use the judicial exception. This could read on mental activity being performed solely in a practitioner’ head, e.g. A mental appreciation of the level of anti-nephrin antibodies being correlated with risk or development of MCD, acute acquired nephrotic syndrome or FSGS or as being ineligible for transplant. No active method steps are invoked or clearly required; the “identifying” statements do not include any activity that would constitute a practical application, i.e. steps that apply, rely on or use the natural principle in a manner such that the claims amount to significantly more that the natural principal itself.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Further, the additional elements of the claims are recited with a high level of generality and do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. (the active method steps/limitations recited in addition to the judicial exceptions themselves) and do not add significantly more to the judicial exception(s).
As shown Ruotsalainen et al (Proc. Natl. Acad. Sci. USA, Vol. 99. Pgs 7962-7967, July 1999) it is well known, routine and conventional in the art to use recombinant full length neprhin (consisting of 1,241 amino acids and comprises the extracellular domain Seq ID NO: 1) (page 7963) to bind to antibodies. As shown by Aaltonen et al Nephrol Dal Transplant, 2007, 22: pages 146-153) it is well known, routine and conventional in the art to obtain a sample from a subject and detect autoantibodies to nephrin with an assay such as radio-immunoassay (e.g. abstract, pg 147). Further, the detection of autoantibodies by western blot, ELISA, protein array, RIA etc is well known, routine and conventional.
With respect to the “administering a treatment for MCD or for an acute acquired nephrotic syndrome or for FSGS to the subject” as recited in claims 2-3. Although the claims invokes administering a treatment to the subject the claim allows for generic treatment of anything already known and available which may include rest and thus does not provide a specific treatment and therefore the step does not add more than the judicial exception.
It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well understood, conventional or routine in the field of diagnostics and biochemical assay methodologies.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
NOTE: If the Applicant were to amend claims 1 and 11 from “comprising amino acids of SEQ ID NO:1” to --consisting of SEQ ID NO: 1--. Then the claim would be considered allowable because use human nephrin protein or extracellular domain consisting of SEQ ID NO: 1 which is recombinantly produced is not well known, routine and conventional in a method a currently recited and thus the limitation would add more than the judicial exception.
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.
Written Description
Claims 1-12 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.
The methodology for determining adequacy of Written Description to convey that applicant was in possession of the claimed invention includes determining whether the application describes an actual reduction to practice, determining whether the invention is complete as evidenced by drawings or determining whether the invention has been set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that applicant was in possession of the claimed invention (Guidelines for Examination of Patent Applications under 35 USC § 112, p 1 “Written Description” Requirement; (Federal Register/Vol 66. No. 4, Friday, January 5, 2001; II Methodology for Determining Adequacy of Written Description (3.)).
Claims 1-12 are broadly drawn, such that they apply to a genus of antigens comprising amino acid of SEQ ID NO: 1. For example, the broad claim allows for an antigen having amino acids and does not place a limit on the number of amino acids it has from SEQ ID. NO:1. However, the working examples provided in the instant application only demonstrate specific species of the extracellular domain of nephrin consisting of amino acids 1-1059 (e.g. pages 18-19) which possess the unique capability of specifically binding to autoantibodies to nephrin in a sample from a subject. Pages 18-19 discloses the extracellular domain of nephrin consisting of amino acids 1-1059. The specification on pages 24-26 discloses ELISA and western blots using the recombinant extracellular domain of human nephrin 1-1059. However, the specification does not disclose a nephrin or domain that comprises amino acids of SEQ ID NO: 1. There is no description of any other nephrin or fragment of nephrin other than that of the extracellular domain consisting of SEQ ID NO:1 (1-1059). Despite the large variety of different types of antigens that may comprise the sequence or the addition of other amino acids to the antigen or deletion of amino acids from any and all possible antigens other than the recited sequences that could be constructed, the specification only cites possession of the specific extracellular domain of nephrin consisting of amino acids 1-1059 of human nephrin which possess the unique capability of specifically binding to autoantibodies in a sample from a subject
It was known in the prior art that small changes in antigen structure profoundly affect antibody-antigen interactions. Harlow & Lane (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26) discuss how even small changes in antigen structure can profoundly affect the strength of an antibody-antigen interaction. See entire selection, in particular page 26, first full paragraph. In particular, the loss of a single hydrogen bond can reduce the strength of interaction by 1000-fold (ibid).
Many other researchers have reported similar findings to those of Harlow & Lane. For example, Lederman et al. ("A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4" Mol Immunol. 1991 Nov;28(11):1171-81) found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (see title and abstract). Similarly, Colman et al. (Research in Immunology, 1994; 145(1): 33-36) teach that amino acid changes in an antigen can effectively abolish antibody antigen binding entirely (see entire document, particularly pages 33-34).
As noted above, the variability among the antigen sequences encompassed by the claims is also enormous; and would encompass changes much more substantial than the loss of a single hydrogen bond or the mutation of a single amino acid; yet even such minor changes as these were known to dramatically affect function.
Given the unpredictability associated with making even minor changes to antigen structure while preserving function, with limited exception it is not possible to predict which, out of the enormous number of peptides encompassed by the claims, would be capable of binding to avian antibodies in a sample.
MPEP § 2163, states “[A] biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
The Revised Interim Guideline for Examination of Patent Applications under 35 USC § 112, p1 “Written Description” Requirement (Federal Register/ Vol 66. No 4, Friday January 5, 2001) states “The claimed invention as a whole may not be adequately described if the claims require an essential or critical element which is not adequately described in the specification and which is not conventional in the art” (column 3, page 71434), “when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus”, “In an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus” (column 2, page 71436, emphasis added).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, 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 the [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Considering the potentially large numbers of sequences encompassed by any and all antigens, the disclosure is not sufficient to show that a skilled artisan would recognize that the applicant was in possession of the claimed invention (genus) commensurate to its scope at the time the application was filed. It appears that the specification is limited to the extracellular domain of nephrin consisting of SEQ ID NO: 1 which possess the unique capability of specifically binding to autoantibodies in a sample from a subject having or who is suspected of having MCD or acute acquired nephrotic syndrome or FSGS.
Response to Arguments
Applicant’s arguments filed 12/18/25 have been considered but are moot in view of the new grounds of rejection.
Allowable Subject Matter
Claims 4-10 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), set forth in this Office action rewritten in independent form including all of the limitations of the base claim and any intervening claims. The specific treatments provided in claim 4 would provide more than the judicial exception recited in claims 1-2. Further, the prior art of record does not teach nor suggest a method as claimed wherein the detected antibodies are correlated with MCD, acute acquired nephrotic syndrome or FSGS.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678