CTNF 18/459,651 CTNF 101190 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 1-14 are pending and examined herein. Priority The present application was filed on 09/01/2023. No priority claimed. Claim Rejections - 35 USC § 112 07-30-01 AIA 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. 07-31-01 AIA Claims 1-14 are r ejected 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. S cope of the invention Claims 1 and 5 recite a monoclonal antibody that “specifically recognizes the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1)”. Claim 2 recites that the monoclonal antibody of claim 1 “specifically binds to the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) and does not specifically bind to a peptide having the N-terminus amino acid sequence HPIQWNAPQPS (SEQ ID NO: 2)”. Claim 3 recites that the monoclonal antibody of claim 1 “specifically binds to the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) and does not specifically bind to a peptide having the N-terminus amino acid sequence IQWNAPQPS (SEQ ID NO: 3)”. Claim 4 recites that the monoclonal antibody of claim 1 “is raised against a synthetic peptide having the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1)”. The claimed antibody therefore may be any of a genus of antibodies, where the antibodies are defined only in terms of desired function (in this case, N-terminus sequence specificity or the sequence it’s raised against). The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of an application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below. Further, 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: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi , 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. Amgen v. Sanofi describes how when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself; not just a description of the sequence to which the antibody binds. Amgen, 872 F.3d at 1378-79. Office guidance requires that adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. See the Memorandum dated February 22, 2018 entitled “Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials” available at https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf . “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)) (emphasis added). “ [A] sufficient description of a genus . . . requires the disclosure of either a representative number* of species falling within the scope of the genus or structural features commo n to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” ( AbbVie , 759 F.3d at 1297, reiterating Eli Lilly , 119 F.3d at 1568-69) (emphasis added). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date ” ( AbbVie , 759 F.3d at 1298, reiterating Enzo Biochem, Inc ., 323 F.3d at 964)(emphasis added). In the present case, however, there is insufficient evidence of such an established structure-function correlation in the case of an antibody having the function of specifically recognizing the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1), and/or does not specifically bind HPIQWNAPQPS (SEQ ID NO: 2) or IQWNAPQPS (SEQ ID NO: 3). Disclosure of drawings or structural chemical formulas/ Actual Reduction to Practice The specification discloses a single species reading on the genus of antibodies (the antibodies produced by hybridoma cell lines as the results of mouse spleen cells fused with SP2/0 myeloma cells) (paragraph [0055]). Relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation The specification does not disclose any partial structure or other identifying characteristics of the antibody, which are responsible for the desired function. The specification fails to disclose, for example, what particular amino acid residues of the antibody are responsible for conferring the desired functional property of binding to the epitope sequence PIQWNAPQPS (SEQ ID NO: 1). In other words, there is no disclosure of any structure/function correlation. The disclosure of a single species, which is not described or identified in terms of the structure/ sequence of the antibodies therein, is not sufficient to reflect the variation within the 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 this functional property. The structural features common to the members of the genus are unknown. A single disclosed species would not put one skilled in the art in possession of any other antibodies having the claimed functional properties. As evidence, see Lloyd et al. ("Modelling the human immune response: performance of a 10e11 human antibody repertoire against a broad panel of therapeutically relevant antigens", Protein Engineering, Design and Selection, Volume 22, Issue 3, 1 March 2009, Pages 159–168, https://doi.org/10.1093/protein/gzn058 ), which shows how a repertoire of 1x10 11 human antibody variable regions can generate large numbers of unique, biologically active scFvs against a variety of polypeptide targets (see e.g., at page 161-62 bridging paragraph and in Table 1, cited herewith). As further illustration of the unpredictability in the art, Brown et al. (“Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation?”, J Immunol. 1996 May;156(9):3285-91), describes how a one amino acid change in the VHCDR2 of a particular antibody was tolerated whereas, the antibody lost binding upon introduction of two amino changes in the same region (at 3290 and Tables 1 and 2). Vajdos et al. (“Comprehensive functional maps of the antigen-binding site of an anti-ErbB2 antibody obtained with shotgun scanning mutagenesis” J Mol Biol. 2002 Jul 5;320(2):415-28, DOI: 10.1016/S0022-2836(02)00264-4) teach that amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (see especially at 416). Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. In view of the above, one cannot visualize or recognize the identities of the members of the genus that exhibit the claimed functional properties. Although Applicants disclose reduction to practice of a single species for the antibody, given the unpredictability of making changes to antigen and/or antibody structures while preserving binding function as above, one cannot envision the structures of those antibodies falling within the claimed genera of antibodies. The characteristics defining the antibody is unknown, as reciting that the antibody is specific for an epitope within a given sequence only sets forth what the antibodies do and not what they are . There is no disclosed partial structure or other common structural features, common to the members of the genus, which are responsible for conferring the desired function. A claimed invention may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule defined solely by its ability to perform a function, such as to serve as an antigen recognizing construct, without a 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 biomolecule of interest . See MPEP 2163, which states that “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 ” (emphasis added). As discussed in the recent case of Amgen Inc. v. Sanofi , 124 USPQ2d 1354 (Fed. Cir. 2017), see page 17: An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad , 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g. , J.A. 1241 (549:5–16) (Appellants’ expert Dr. Eck testifying that knowing “that an antibody binds to a particular amino acid on PCSK9 . . . does not tell you anything at all about the structure of the antibody”); J.A. 1314 (836:9–11) (Appellees’ expert Dr. Petsko being informed of Dr. Eck’s testimony and responding that “[m]y opinion is that [he’s] right”); Centocor , 636 F.3d at 1352 (analogizing the antibody- antigen relationship as searching for a key “on a ring with a million keys on it”) (internal citations and quotation marks omitted). Amgen Inc. v. Sanofi further notes, pointing to Ariad Pharms., Inc. v. Eli Lilly & Co. , 94 USPQ2d 1161 (Fed Cir. 2010): To show invention, a patentee must convey in its disclosure that it “had possession of the claimed subject matter as of the filing date.” Id. at 1350. Demonstrating possession “requires a precise definition” of the invention. Id. To provide this “precise definition” for a claim to a genus, a patentee must disclose “a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. Amgen at pages 7-8. In this case, the disclosure of a single species is insufficient to represent the claimed genus of antibodies having the recited functional properties. There is no disclosed partial structure or other common structural features, common to the members of the genus, which are responsible for conferring the desired function. Recent court cases have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See AbbVie Deutschland GmbH v. Janssen Biotech. Inc . as well as Amgen v. Sanofi , as discussed above. Indeed, in Amgen the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e. the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship be analogized as a search for a key on a ring with a million keys on it. The description requirement of the patent statue 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.”). Level of skill and knowledge in the art/predictability in the art The level of skill in the art is high. In particular, methods for making and/or screening monoclonal antibodies with desired binding properties were well known in the art at the time of the invention. At the same time, however, it was not within the skill of the art to predict whether a given antibody would bind specifically to a particular epitope. In summary, the specification fails to provide adequate written description for the genus of the antibody claimed, as the antibody is described only in terms of desired functional properties and not in terms of common structure or other relevant identifying characteristics to define the genus. The specification does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention . Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 6-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception and a law of nature without significantly more. Claim 6 recites “ The method as claimed in claim 5, wherein the method is a method of immunoassay for detecting and/or monitoring a fibrotic disease or a particular level of severity thereof in a patient, the method further comprising; iii) correlating said amount of binding with values associated with normal healthy subjects and/or values associated with known disease severity and/or values obtained from said patient at a previous time point and/or with a predetermined cut-off value. ”. Claim 7 recites “ The method as claimed in claim 6, wherein the fibrotic disease is idiopathic pulmonary fibrosis ”. The steps are judicial exceptions because they are merely observing naturally occurring correlations (laws of nature/natural correlation). This judicial exception is not integrated into a practical application because there is no practical application recited in the claims such as performing the treatment in a way that is particular, and not merely instructions to "apply" the exception in a generic way. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional steps amount to mere data gathering that does not go beyond well-understood, routine, and conventional activity; as detailed below. Step 1 – Whether a claim is to a statutory category - YES The instantly claimed invention is directed toa method of immunoassay to detect and/or monitor a fibrotic disease by correlating the amount of antibody binding to a peptide in a sample from and afflicted patient with the amount of binding in a sample from a healthy patient, or in comparison to the afflicted patients prior samples.. Claim 7 teaches the method of claim 6, wherein the fibrotic disease is idiopathic pulmonary fibrosis. Therefore, the instantly claimed invention falls into one of the four statutory categories. Step 2A Prong 1 – Whether the claim is directed to a judicial exception (i.e. Does the claim recite an abstract idea, law of nature, or natural phenomenon?) - YES Claims 6 and 7 recite the following steps which fall under the law of nature and/or mathematical concepts grouping of abstract ideas: Claim 6 discloses “ The method as claimed in claim 5, wherein the method is a method of immunoassay for detecting and/or monitoring a fibrotic disease or a particular level of severity thereof in a patient, the method further comprising; iii) correlating said amount of binding with values associated with normal healthy subjects and/or values associated with known disease severity and/or values obtained from said patient at a previous time point and/or with a predetermined cut-off value ”. Claim 5 merely teaches a method of immunoassay where a sample is brought into contact with a monoclonal antibody that specifically binds to the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) in order to detect and determine the amount of binding between said monoclonal antibody and peptides in the sample. Claim 7 teaches the method of claim 6, wherein the fibrotic disease is idiopathic pulmonary fibrosis. The broadest reasonable interpretation of this step is “determining” the amount of peptide binding to the antibody in the patient sample and “correlating” the amount of binding with values from a healthy subject and/or associated with known disease severity and/or values obtained from said patient at a previous time point and/or with a predetermined cut-off value. This is done to determine if a patient has a fibrotic disease (taught as idiopathic pulmonary fibrosis in claim 7) or to monitor the severity or progression of the disease, which are abstract ideas, specifically, abstract mental processes. Regarding the step of “correlating”, the courts have held similar claims to be abstract mental processes, as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014) which involved claims to "comparing BRCA sequences and determining the existence of alterations," where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind. The claims are also similar to that in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011), which involved a claim to “collecting and comparing known information” (both of these court cases are discussed in MPEP 2106.04(a)(2) (II)(A)). The step of “determining” also constitutes an abstract mental process, involving assessing the comparison of expression levels of the biomarker in a test sample, and then making an evaluation or judgment as to whether the test subject has a particular disease. The “comparing” and “determining” steps could be performed in the human mind, or by a human using pen and paper, insofar as it reads on comparing levels and drawing conclusions from this about the health status of a subject. Furthermore, the “detecting” step can also be regarded as a law of nature, namely, the naturally occurring correlation between levels of the peptide bound by the monoclonal antibody and fibrotic disease. Thus, claim 1 falls into a judicial exception. Step 2A: Prong 2 - Does the claim recite additional elements that integrate the judicial exception into a practical application? The Step 2A, Prong 2 analysis requires identifying whether there are any 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. Claims 6 and 7 do not recite any additional element that integrate the exception into a practical application of the exception. The additional steps of comparing binding amounts with a predetermined cut-off value or amounts at a previous sampling point are insufficient to integrate the exception into a practical application because the purpose is merely to obtain data. As in In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989), such activity involving performing clinical tests on individuals constitutes mere data gathering, and does not go beyond insignificant extra-solution activity. See MPEP §§ MPEP 2106.04(d)(I) and 2106.05(g). There are no subsequent steps recited after the “determining” or “correlating” step that would practically apply the method depending on the results of the measurements, e.g., treatment or other process steps that are performed after the test subject has been diagnosed with a disease. Step 2B ; Whether the additional elements contribute an “inventive concept”. In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP 2106.05. Briefly, the claims 6-7 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because of the following reasons. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, has been found to be insufficient to add “significantly more” (MPEP 2106.05(I)(A)). The additional steps of claims 6-7, do not add a meaningful limitation to the instant method as they would have been routinely used by those of ordinary skill in the art as supported by Chernousov et al. (1991) . “Role of the I-9 and III-1 modules of fibronectin in formation of an extracellular fibronectin matrix”. Journal of Biological Chemistry , 266 (17), 10851-10858, in view of Hood et al. (US 2014/0106981 A1), Zheng et al. (2011) . “The first type III domain of fibronectin is associated with the expression of cytokines within the lung tumor microenvironment”. Journal of cancer , 2 , 478, Gardiner et al. (U.S. 2007/0037158 A1) and Kolaskar et al. (1990) . “A semi-empirical method for prediction of antigenic determinants on protein antigens”. FEBS letters , 276 (1-2), 172-174, and Maher et al. (2019) . “An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study”. Lancet Respir Med. 2017; 5: 946–55. Lancet Respir Med , 7 (9), 771-779. Regarding claims 6-7, Chernousov in view of Hood, Zheng, Gardiner and Kolaskar teaches a monoclonal antibody that specifically binds to the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) and does not specifically bind to a peptide having the N-terminus amino acid sequence HPIQWNAPQPS (SEQ ID NO: 2) or IQWNAPQPS (SEQ ID NO: 3), and is raised against a synthetic peptide having the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) Maher teaches a method of performing immunoassays in order to monitor and identify individuals with IPF (a fibrotic disease) who were at risk of progression or death (Summary – Methods). This method compared biomarker values between IPF and normal healthy subjects, as well as compared values between sampling timepoints in both the IPF and healthy groups (page 951, column 1, 1 st paragraph). See a detailed discussion of what these references teach in the prior art rejections below. For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s). Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to a law of nature and abstract idea without significantly more. For additional guidance, applicant is directed generally to MPEP § 2106. Claim Rejections - 35 USC § 103 07-20-aia AIA The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. 07-21-fti Claim s 1-4 are a rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Chernousov et al. (1991) . “Role of the I-9 and III-1 modules of fibronectin in formation of an extracellular fibronectin matrix”. Journal of Biological Chemistry , 266 (17), 10851-10858, in view of Hood et al. (US 2014/0106981 A1), Zheng et al. (2011) . “The first type III domain of fibronectin is associated with the expression of cytokines within the lung tumor microenvironment”. Journal of cancer , 2 , 478, Gardiner et al. (U.S. 2007/0037158 A1) and Kolaskar et al. (1990) . “A semi-empirical method for prediction of antigenic determinants on protein antigens”. FEBS letters , 276 (1-2), 172-174, and in light of the evidence from “Epitope prediction and Analysis Tools” at the URL IEDB Analysis Resource, results obtained by the examiner on 3/25/2026 using sequence pdb_00001oww . Regarding claims 1-4 , Chernousov teaches the analysis of antifibronectin monoclonal antibodies to identify fibronectin domains required for assembly into matrix (abstract). Chernousov teaches a method of immunoblotting fibronectin fragments and identification of an epitope for the monoclonal antibody (9D2) which is in the first fibronectin type III homology sequence (III-1) (abstract) from which the peptide anastellin originates. However, Chernousov is silent on whether the monoclonal antibody specifically recognizes the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) of the first fibronectin type III homology sequence, or whether it does not specifically bind to a peptide having the N-terminus amino acid sequences HPIQWNAPQPS (SEQ ID NO: 2) and/or IQWNAPQPS (SEQ ID NO: 3). Zheng teaches the analysis of a partially unfolded intermediate peptide of the first Type III repeat of human fibronectin (i.e. anastellin) on inflammatory gene expression in adult human lung fibroblast cells (abstract). Zheng teaches that anastellin induced expression of inflammatory mediators such as cytokines, CXCL1-3, IL-8 and TNF-α, by lung fibroblast cells (abstract). Zheng also teaches that this release of cytokines from lung fibroblasts may promote tumor progression through chronic inflammation (page 481, column 2, 2 nd full paragraph). Hood teaches organ-specific proteins and the polynucleotides that encode them [006]. Hood also teaches diagnostic and prognostic panels using reagents or probes to detect these organ specific proteins in a biological sample from subjects with a disease that affects the organs from which the proteins are derived (page 100, claim 1). Furthermore, Hood teaches a polynucleotide sequence 16 amino acids in length which encodes part of the human fibronectin first type III repeat (SEQ ID NO: 38448), which contains the entirety of SEQ ID NOs: 1-3 from the instant application. Gardiner et al. teach art-recognized methods for making antibodies [0225-0236]. In particular, Gardiner et al. teach how peptide fragments can be used as immunogens and injected into host animals to produce monoclonal antibodies [0225-0229]. Preferably, an antibody raised to such an immunogen also recognizes the full-length protein from which the immunogen was derived, such as, for example, in its native state or having native conformation [0239]. Peptide immunogens may be predicted using an algorithm such as that described in Kolaskar [0233]. Kolaskar teaches an easy-to-use semi-empirical method of predicting antigenic determinants on proteins, based on the properties and frequencies of occurrence of experimentally know epitopes (abstract). Kolaskar teaches that this method can predict antigenic determinants with about 75% accuracy (abstract). A program using this method is available to use free of charge and is located at the website "IEDB Analysis Resource" under “Epitope prediction and Analysis Tools” at the URL IEDB Analysis Resource. This URL offers a web-based program for running the referenced program, based on a protein sequence that is input by the user (see attached evidence entitled “Predicted Antigenic Peptides”, wherein the examiner input the 98-amino acid sequence for first type III module of human fibronectin which was known in the art (pdb_00001oww, obtained from RCSB PDB - 1OWW: Solution structure of the first type III module of human fibronectin determined by 1H, 15N NMR spectroscopy). The program output several antigenic determinants in the sequence, one of which is the 10 aa sequence taught by the instant application SEQ ID NO: 1. Given that procedures for raising monoclonal antibodies were well-developed at the time of the instant invention, as taught for example by Gardiner et al., it would have been obvious to one of ordinary skill in the art to have obtained a monoclonal antibody that specifically recognizes the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) and does not specifically bind to a peptide having the N-terminus amino acid sequences HPIQWNAPQPS (SEQ ID NO: 2) and/or IQWNAPQPS (SEQ ID NO: 3) as recited in the instant application using no more than conventional procedures. Armed with the amino acid sequence for the first type III module of human fibronectin, one skilled in the art could have readily obtained a monoclonal anti-human calcitonin antibody which specifically recognizes the instant application SEQ ID NO: 1, that does not specifically bind SEQ ID NOs: 2-3. One would be motivated to obtain a monoclonal antibody that specifically recognizes the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1), because the peptide encoded by this sequence (anastellin) seems to play a significant role in disease progression and chronic inflammation, as taught by Zheng. Furthermore, Gardiner et al. teach how peptide fragments can be used as immunogens, and that such peptide immunogens can be predicted using an algorithm such as that described in Kolaskar. There was also in existence a web-based program publicly available for predicting antigenic peptides based on this same algorithm of Kolaskar. As can be seen in the attached results obtained by the examiner, when employing this web-based program to predict antigenic peptides in first type III module of human fibronectin, one of the antigenic results obtained was for the sequence PIQWNAPQPS (SEQ ID NO: 1) recited in claim 1 and 5 of the instant application. One skilled in the art could have relied upon no more than art-recognized procedures and available knowledge in the art. One would also have been motivated to choose this course of action for the convenience of using a web-based program for predicting antigenic peptides, and particularly one that was recognized to have about 75% accuracy (as taught by Kolaskar). In summary, art-recognized procedures for raising antibodies were known in the art to include predicting antigenic peptides based on protein sequence information, and specifically by using the algorithm of Kolaskar which was available at the time of the instant invention as a web-based program (see discussion of Gardiner and Kolaskar above). The evidence further indicates that one skilled in the art using this known technique to predict antigenic peptides useful for antibody production against the peptide anastellin would have obtained the sequence PIQWNAPQPS (SEQ ID NO: 1) listed in claim 1 and 5 of the instant application . 07-22-aia AIA Claim s 5-13 are rejected under 35 U.S.C. 103 as being unpatentable over Chernousov in view of Hood, Zheng, Gardiner and Kolaskar as applied to claim s 1-4 above, and further in view of Maher et al. (2019) . “An epithelial biomarker signature for idiopathic pulmonary fibrosis: an analysis from the multicentre PROFILE cohort study”. Lancet Respir Med. 2017; 5: 946–55. Lancet Respir Med , 7 (9), 771-779 . The teachings of Chernousov in view of Hood, Zheng, Gardiner and Kolaskar are incorporated herein. Regarding claims 5, and 9-11 , Chernousov in view of Hood, Zheng, Gardiner and Kolaskar teaches a monoclonal antibody that specifically binds to the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) and does not specifically bind to a peptide having the N-terminus amino acid sequence HPIQWNAPQPS (SEQ ID NO: 2) or IQWNAPQPS (SEQ ID NO: 3), and is raised against a synthetic peptide having the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1) as discussed in the above rejection. However, Chernousov in view of Hood, Zheng, Gardiner and Kolaskar does not teach a method of immunoassay for detecting and/or monitoring a fibrotic disease. Maher teaches a longitudinal study of patients with idiopathic pulmonary fibrosis (IPF) that have not received treatment (Summary – Methods). In Maher, immunohistochemical assessment of IPF lung tissue was performed to investigate promising novel biomarkers (Summary – Methods). Maher also teaches the measurement of these biomarkers in patient samples via immunoassays, which were analyzed to determine which were predictive of IPF patients that were at risk of disease progression or death (Summary – Methods). Regarding claims 5, 8, 12-13 , Maher teaches the method of measuring biomarkers in patient serum samples via sandwich ELISAs according to standard operating procedures (page 948, column 1, 2 nd full paragraph). It is known in the art that the standard operating procedure for immunoassays/sandwich ELISA entails contacting a sample with an antibody, then detecting and determining the amount of binding between said monoclonal antibody and peptides in the sample. Regarding claims 6-7 , Maher teaches a method of performing immunoassays in order to monitor and identify individuals with IPF (a fibrotic disease) who were at risk of progression or death (Summary – Methods). This method compared biomarker values between IPF and normal healthy subjects, as well as compared values between timepoints in both the IPF and healthy groups (page 951, column 1, 1 st paragraph). It would have been obvious to person of ordinary skill in the art before the effective filing date of the claimed invention to have used the modified method taught by Chernousov in view of Hood, Zheng, Gardiner and Kolaskar to make a monoclonal antibody as discussed above and to use such an antibody in an immunoassay for detecting and/or monitoring idiopathic pulmonary fibrosis or a particular level of severity thereof in a patient, as disclosed in Maher. It would be obvious to use a monoclonal antibody produced by the method of Chernousov in view of Hood, Zheng, Gardiner and Kolaskar to detect a biomarker for the diagnosis of IPF because monoclonal antibodies are well known in the art for their wide application in detecting and identifying serum analytes, cell markers, and pathogenic agents, which has largely arisen through the specificity of these unique antibody reagents. The continuous culture of hybridoma cells that produce these antibodies offers the potential of an unlimited supply of reagent. A skilled artisan would have been motivated to use a monoclonal antibody to detect biomarkers proteins that are reflective of epithelial dysfunction and/or inflammation such as taught by Maher (page 946, column 2, 1 st paragraph). Maher discloses the importance of detecting IPF which is a fatal disorder with variable disease trajectory and should be closely monitored (Summary – Background). In addition, Maher discloses that biomarkers that could be used to stratify therapy and provide robust response measures are urgently needed (page 946, column 1, 1 st paragraph) . 07-21-aia AIA Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Chernousov, Hood, Zheng, Gardiner and Kolaskar in view of Zuk et al. (U.S. Patent No. 4208479) and Välimaa et al. (2006). “ Comparison study of streptavidin-coated microtitration plates”. Journal of immunological methods , 308 (1-2), 203-215 . Regarding claim 14, Chernousov, Hood, Zheng, Gardiner and Kolaskar makes obvious the monoclonal antibody of claim 1 as discussed above, but does not recite the antibody in an immunoassay kit, in addition to at least one of: a streptavidin coated well plate; a biotinylated peptide PIQWNAPQPS-L-Biotin (SEQ ID NO: 4), wherein L is an optional linker; a secondary antibody for use in a sandwich immunoassay; a calibrator protein comprising the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1); an antibody biotinylation kit; an antibody HRP labelling kit; or an antibody radiolabelling kit. Zuk et al. teaches the convenience and accuracy enhancement associated with combining all necessary reagents for an assay together in a kit (column 22, lines 20-68). Välimaa et al . teaches the comparison of Streptavidin (SAv)-coated 96-well microtitration plates from commercial suppliers in respect to their binding capacity, leaching, well-to-well variation, and immunoassay performance (abstract). Therefore, it would have been obvious to one of ordinary skill in the art to assemble together the reagents (monoclonal antibody that specifically binds to the N-terminus amino acid sequence PIQWNAPQPS (SEQ ID NO: 1), streptavidin coated well plate, and standard immunoassay reagents) in the form of a kit, in order to create an assay kit that can quantify the peptide that is bound by the antibody of instant claim 1 described by Chernousov, Hood, Zheng, Gardiner and Kolaskar. A skilled artisan would have had a reasonable expectation of success in assembling the reagents of the patented claims into kits as taught by Zuk because kits are well known as being convenience and economical. Conclusion For all the reasons discussed above, claims 1-14 are rejected and therefore no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDER JOSEPH HOFFMAN whose telephone number is (571)272-9080. 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Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ALEXANDER J. HOFFMAN/ Examiner, Art Unit 1677 /BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 March 31, 2026 Application/Control Number: 18/459,651 Page 2 Art Unit: 1677 Application/Control Number: 18/459,651 Page 3 Art Unit: 1677 Application/Control Number: 18/459,651 Page 4 Art Unit: 1677 Application/Control Number: 18/459,651 Page 5 Art Unit: 1677 Application/Control Number: 18/459,651 Page 6 Art Unit: 1677 Application/Control Number: 18/459,651 Page 7 Art Unit: 1677 Application/Control Number: 18/459,651 Page 8 Art Unit: 1677 Application/Control Number: 18/459,651 Page 9 Art Unit: 1677 Application/Control Number: 18/459,651 Page 10 Art Unit: 1677 Application/Control Number: 18/459,651 Page 11 Art Unit: 1677 Application/Control Number: 18/459,651 Page 12 Art Unit: 1677 Application/Control Number: 18/459,651 Page 13 Art Unit: 1677 Application/Control Number: 18/459,651 Page 14 Art Unit: 1677 Application/Control Number: 18/459,651 Page 15 Art Unit: 1677 Application/Control Number: 18/459,651 Page 16 Art Unit: 1677 Application/Control Number: 18/459,651 Page 17 Art Unit: 1677 Application/Control Number: 18/459,651 Page 18 Art Unit: 1677 Application/Control Number: 18/459,651 Page 19 Art Unit: 1677 Application/Control Number: 18/459,651 Page 20 Art Unit: 1677 Application/Control Number: 18/459,651 Page 21 Art Unit: 1677 Application/Control Number: 18/459,651 Page 22 Art Unit: 1677