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 .
Status of the Claims
Claims 1-17 are pending in the application.
Claims 13-17 are withdrawn.
Claims 1-12 are the subject of this office action.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12 in the reply filed on 15 June 2026 is acknowledged.
Claims 13-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 15 June 2026.
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 1-12 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 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
Claim 1 recites: “a monoclonal antibody that specifically binds to an N-terminus amino acid sequence DAPGQYGAYF (SEQ ID NO: 2)”. As such, the claims encompass a broad genus of monoclonal antibodies which are defined by their particular binding function (wherein binding function is further limited in claims 8-10).
Regarding the functional limitation that the monoclonal antibody binds to a particular amino acid sequence, the disclosure does not provide description of a particular structural feature that imparts the claimed monoclonal antibody with the particular claimed function. Rather, the specification only describes the structure of particular amino acid sequences to which the monoclonal antibody does or does not bind, without describing the structure of the antibody itself that is responsible for imparting the critical binding function.
Although the specification discloses reduction to practice of one species of antibody which displays the recited binding functions, the specification does not identify any partial structure (beyond generic description of a monoclonal antibody) or other identifying characteristics that are responsible for imparting the claimed binding function. The claims and specification fail to disclose, for example, what particular amino acid residues of the antibody are responsible for conferring the desired functional property of binding (or not binding) to a particular amino acid sequence.
Describing the structure of an epitope to which an antibody specifically binds or does not specifically bind is insufficient to describe the genus of antibodies themselves, since there is no structure-function correlation either disclosed or known in the art (as discussed below, antibody sequence does not correlate to binding in a predictable fashion). Accordingly the disclosure of a single species of antibody is not sufficient to reflect the breadth and variation within the claimed genus. A skilled artisan, cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that would exhibit the claimed binding functions. The structural features common to the members of the genus are unknown.
Accordingly, the disclosure fails to describe a representative number of species given the lack of a known or disclosed structure-function correlation in the case of antibodies binding to a particular amino acid sequence. The disclosure of a single species of antibody that displays the recited binding functions would not put on or ordinary skill in the art in possession of any other antibodies having the same functional properties.
Additionally, there is a general lack of structure-function correlation for the claimed antibodies. The general structure of antibodies was known in the art before the effective filing date. It was known that the CDRs of antibodies generally control their antigen binding. While CDRs are necessary for binding, they are highly diverse in structure, and their sequences do not correlate to binding in a predictable fashion. See for instance:
Goel et al. (“Plasticity within the Antigen Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response,” The Journal of Immunology (2004), 173(12):7358-7367), who made three antibodies that bind to the same 12-mer but have very different CDRs.
Lloyd et al. (“Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens,” Protein Engineering, Design & Selection (2009), 22(3):159-168) found that on average, about 120 different antibodies in a library can bind to a given antigen.
Edwards et al. (“The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BlyS,” Journal of Molecular Biology (2003), 334:103-118) found that a library contained over 1000 antibodies that bound to a single 51 kDa protein, including 1098 unique VH and 705 VL sequences. There were 568 different CDR3 regions, indicative of high diversity.
These references indicate that there was no art-recognized correlation between the structure of an antibody and its binding properties. A single antigen can be bound by a very large and structurally diverse genus of antibodies. There is no common structural relationship even for antibodies that bind to the same protein sequence or even to the same epitope. Although the specification discloses antibodies that perform the claimed binding functions, the specification does not describe the structural characteristics common to the genus of antibodies that display the claimed binding functions. The specification does not provide guidance as to what essential structures of antibodies would confer the necessary binding functions and does not allow one of ordinary skill in the art to visualize or recognize the members of the genus of antibodies that would be able to achieve the claimed binding function.
Given the breadth of the claims, the lack of either a disclosed or art-recognized correlation between structure and function for the claimed genus of antibodies, and the unpredictability of the art, one of ordinary skill in the art would not have envision possession of the claimed genus of antibodies based on the instant disclosure.
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.
Claims 2-5 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.
Claim 2 is rejected as indefinite because the metes and bounds of the claim are unclear. The claims recites “correlating said amount of binding with values associated with normal healthy subjects and/or values associated with a known disease severity and/or values obtained from said patient at a previous time point and/or with a predetermined cut-off value”. Multiple parameters and terms of the recitation are unclear. The “values” are not defined and it is not clear what these represent. The phrasing “correlating” and “associated with” do not create a clear relationship between the amount of binding and the recited values, such that the metes and bounds of what this step requires are unclear, and the “predetermined cut-off value” is undefined. Clarification is required.
Claims 3-5 are rejected as indefinite because they depend from an indefinite claim and fail to remedy its deficiencies.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-5 and 10 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 3-5 depend from claim 2, however the only limitations recited in these claims are directed to the intended use of the method of claim 2 (i.e. the claims recite that the method is a method for detecting and/or monitoring particular fibrotic kidney disease. Such statements of intended use merely define the context in which the invention operates and do not limit the scope of the claim or distinguish it over the prior art. The statements merely express the purpose of the claimed method and fail to clearly result in a manipulative difference.
Claim 10 depends from claim 1 which is an immunoassay method, however claim 10 only recites limitations regarding the method of producing the monoclonal antibody. The method of producing the monoclonal antibody is distinct from the method of immunoassay and therefore fails to limit the method of immunoassay of claim 1, as the method of producing the monoclonal antibody is not part of the method of immunoassay and does not appear to result in any manipulative difference in the method of immunoassay.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Subject Matter Free of Prior Art
Claims 1-12 are rejected as described above, but appear to be free of the prior art.
The closest prior art is Laursen et al (A Novel Non-Invasive Biomarker Targeting LG3 From Perlecan Can Identify Lupus Nephritis (LN) Patients and Differentiate LN Subclasses: TH-PO429. Journal of the American Society of Nephrology 33(11S):p 166, November 2022).
Laursen teaches a method of immunoassay comprising:
contacting a patient sample with a monoclonal antibody that specifically binds to an N-terminus amino acid sequence of LG3 generated by BMP-1 cleavage 2; and detecting and determining an amount of binding between said monoclonal antibody and peptides in the sample (Background, Methods: ELISA using a monoclonal antibody specifically targeting the N-terminal site of LG3 generated by BMP-1 cleavage allows user to measure LG3 in a patient sample and distinguish LG3 from endorepellin or intact perlecan).
It is noted that the monoclonal antibody of the instant claim is described in the instant specification to have the same binding function and specificity of the instantly claimed antibody (see, e.g. specification Par. 2, 7, 10), however Laursen fails to meet the instant claim because it does not explicitly teach that the disclosed monoclonal antibody specifically binds to the N-terminus amino acid sequence DAPGQY GAYF (SEQ ID NO: 2), thus it is not possible to conclude that the antibody disclosed by Laursen meets all the limitations of the instant claim.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLIS LUSI whose telephone number is (571)270-0694. The examiner can normally be reached M-Th 8am-6pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached at (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677
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