DETAILED ACTION 1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. 2 Applicant's amendment, filed on 10/10/2023 , is acknowledged. 3. Claims 13-32 are pending. 4 . Applicant’s IDS, filed 01/09/2024 , is acknowledged. 5 . The following is a quotation of 35 U.S.C. 112(b) (Pre AIA, 35 U.S.C. 112, second paragraph): (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. 6 . Claim s 19 and 29 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. (a) the recitation “conjugates having antibody CDR regions” in claim 19 is indefinite because the recitation does not further limit the antibody recited in claim 1. It is not clear how the antibody in claim 1 is now conjugates. Furthermore, it is not clear how is the antibody is now CDRs. ( b ) The recitation “the selective targeting agent” in claim 29 lacks sufficient antecedent basis in base claim 1, base claim 1 only recites antibody. 7 . The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph): (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. 8 . Claims 13 - 32 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. Claims 13-18 encompasses a broad genus of antibody which is capable of binding MFAP4 and inhibiting MFAP4-integrin interaction and preventing, alleviating and/or treating fibrosis including liver fibrosis, chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury . Claim 19 encompasses a genus of anti-MFAP4 antibodies including polyclonal antibodies, monoclonal antibodies, chimeric antibodies, a fully human antibody, a humanized antibody, a humanized monoclonal antibody, an antibody wherein the heavy chain and light chain are connected by a flexible linker, single chain antibodies, Fc fragments, Fv fragments, scFv fragments, diabody, triabody , Fab fragments, Fab' fragments, F(ab')2 fragments, conjugates having antibody CDR regions, nanobodies, fusion proteins, and a Fab expression library . Claim s 20 - 21 encompass up to 20% variation in the VL and VH of SEQ ID NOs: 1-8. Claim s 20- 2 2 encompass a genus of anti-MFAP4 antibodies that mix and match between different anti-MFAP4 antibody VHs and VLs having different epitope recognition, different affinity and different in inhibiting MFAP4-integrin interaction. Claim 24 encompass up to up 3 amino acids modifications in each of the VL-CDR1-3 of SEQ ID NOs: 9-11 and in each of the VH-CDR1-3 of SEQ ID NOs: 12-14. Claim 25 encompasses up to 10% variations in the VL of SEQ ID NOs: 1, 3 and up to 10% variations in the VH of SEQ ID NO: 2 and 4. However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of inhibiting MFAP4-integrin interaction and preventing, alleviating and/or treating fibrosis including liver fibrosis, chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury . The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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. The specification at page 17, under antibodies, discloses that a n antibody for targeting MFAP4 is also mentioned as anti-MFAP4 herein. These antibodies may have different sequences and different binding properties but they are able to bind to MFAP4 and capable of preventing MFAP4 from binding to integrins. The specification at page 26, 1 st ¶ discloses that m onoclonal antibodies with affinity for hrMFAP4 were produced using standard hybridoma technique and MFAP4 deficient mice. This procedure resulted in a series of monoclonal antibodies including: - HG Hyb 7-5 murine monoclonal antibody raised against human recombinant MFAP4 (hrMFAP4) (described e.g. in WO 2014/114298) - HG Hyb 7-14 murine monoclonal antibody raised against human recombinant MFAP4 (hrMFAP4) (described e.g. in WO 2014/114298) - HG Hyb 7-18 murine monoclonal antibody raised against human recombinant MFAP4 (hrMFAP4) (described e.g. in WO 2014/114298) - m AS0326 murine monoclonal antibody raised against human recombinant MFAP4 (hrMFAP4) and chosen antibody for humanization - h AS0326 humanized monoclonal antibody (described e.g. in WO 2019/086580) - h AS0326 Fc-neutralized humanized monoclonal antibody, which is similar to hAS0326, except for point mutations in the Fc-domain of the heavy chain. These point mutations were introduced using standard techniques as known to the persons skilled in the art. It is noted that human MFAP4 is 2 55 amino acid s in length. It is well known in the art that the epitope binding site of an antibody is usually defined by no more than six to eight amino acids. Neither the instant specification nor the art of record shows that the majority of antibodies that bind to any one of the multitude of epitopes present in a protein having the sequence of MFAP4 are capable of inhibiting MFAP4-integrin interaction and preventing, alleviating and/or treating fibrosis including liver fibrosis, chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury , as is required for the operability of the claimed product. The required genus is not adequately described because neither the specification nor the art of record describes a representative number of species of antibody within the required genus. Artisans are well aware that knowledge of a given antigen (for instance MFAP4 ) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al (J Mol Biol. 2003 Nov 14;334(1): 103-18 ) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the FICDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document). Similarly, Lloyd et al (Protein Eng Des Sel. 2009 Mar;22(3):159-68) teach that a large majority of VH/VL germline gene segments are used in the antibody response to an antigen, even when the antibodies were selected by antigen binding, as their sequencing studies revealed that out of 841 unselected and 5,044 selected antibodies, all but one of the 49 functional VH gene segments was observed (see entire document). Goel et al (J Immunol. 2004 Dec 15; 173(12):7358-67) disclose the synthesis of three mAbs that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (see entire document). As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data such as that of Edwards et al. indicating the diversity of sequence bound in a population of antibodies that bind to a given antigen no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen. Indeed, Kanyavuz et al (Nat Rev Immunol. 2019 Jun; 19(6):355-368) teach that “Theoretically, under physiological conditions, the human immune system can generate BCRs with 10 26 distinct sequences, an astronomical number that is far greater than the calculated number of all B cell clones that can be generated during the lifespan of a healthy human (estimated to be 4 x 10 14 ). Importantly, the USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018. See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf . The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following. “I n view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”. In contrast to applicant’s reliance of describe the epitope of the MFAP4 in providing a fully characterized antigen / specific epitope as well as claiming structural elements of the antigen, one or more functions recited in the claims, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti- MFAP4 antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi , 124 USPQ2d 1354 (Fed. Cir. 2017). There is no evidence that knowledge of the chemical structure of an antigen gives the required kind of structure identifying information about the corresponding antibodies Applicants attempt to describe the invention by describing something that is not the invention: viz., the antigens to which the antibodies may bind. There nothing in the disclosure that describes the antibodies as required by the test set forth in Ariad. However, the anti- MFAP4 antibodies are required to practice the invention. The specification fails to provide any specific structural or physical information so as to define a genus of antibodies having the desired therapeutic properties. Applicant is merely rely on the identification of MFAP4 as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. However, Federal Circuit clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The claims are directed to a genus of anti- MFAP4 antibodies. However, Federal Circuit clarification of the law of written description as it applies to antibodies. T he 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. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti- MFAP4 antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC , No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e. the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function. Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester , 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of anti- MFAP4 antibodies falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly , 119F.3d at 1568, 43 USPQ2d at 1406. The scope of claims 23-26 encompass fragments of the VL and VH of SEQ ID NOs: 1-8 and the CDRs of SEQ ID NOs: 9-14. The claims 23-26 are generic with respect to size, encompassing any thing from dimers on up of the claimed SEQ ID NOs: 1-14 . The claim language does not impose some lower limit on the size of what is encompassed by the term “ having a light/heavy chain variable region according to SEQ ID NO:” and “comprising a CDR x region according to SEQ ID NO:X” . The claims encompass a genus of VH/VL and CDRs fragments incorporated into any larger amino acid sequence, antibody. The claims encompass fragments that, in addition to the tetra-, penta-, hexa-, hepta-, octa-, nona -, deca - and undeca-peptide recited in SEQ ID NO: 1-14 , also have flanking VH and VL of considerable size up to 120 amino acids in length. However, every member of that genus does not include a common structural feature of the sequence recited in SEQ ID NOs. There are no drawings or structural formulas disclosed of VH/VL polypeptide fragment that binds to MFAP4. There are no teachings in the specification regarding which amino acid of VH and VL polypeptide fragment that can be deleted while retaining the ability of the fragment to bind to MFAP4 . Further, there is no art-recognized correlation between any structure of the VH/VL polypeptide fragment and the activity of binding to MFAP4 , based on which those of ordinary skill in the art could predict which amino acids can be deleted from a VH/VL polypeptide fragment without losing the binding to MFAP4 . Consequently, there is no information about which amino acids can deleted from any VH/VL and CDRs polypeptide fragment in the claimed genus of antibodies and still retain the ability to bind MFAP4 . It is suggested the claim recites “ having the light/heavy chain variable region according to SEQ ID NO:” and “comprising the CDRx region according to SEQ ID NO:X” to overcome th is part of rejection. The scope of the claim s 20-22 encompass antibodies comprising mixing and matching the VL and VH from 4 different anti-MFAP4 antibodies having different binding epitope, different affinity, different inhibiting rate of NFAP4-integrin interaction: m AS0326 (SEQ ID NOs: 1-2) , h AS0326 (SEQ ID NOs: 3-4), HG-HYB 7-14 (SEDQ ID NO: 5-6) and HG-HYB 7-5 (SEQ ID NO: 7-8); as well as up to 20% modifications in the VL and VH of SEQ ID NOs: 1-8. Claims 24 and 26 encompass anti-MFAP4 antibod ies comprising up to 3 residues modification in each and every VL and VH CDRs of SEQ ID NO: 9-14 o r up to 10% modifications in the VL and VH of m/h AS0326 of SEQ ID NOs: 1/3 and 2/4. The specification provides three anti- MFAP4 antibod ies , AS0326 (mouse and humanized) , HG-HYB 7-14 and HG-HYB 7-5 , which were not random combinations of VH and VL i.e., they had specific VH domain (SEQ ID NO: 2, 4, 6, 8 and 3) paired with specific VL domain (SEQ ID NO: 1, 3, 5, 7 , respectively). No other VH/VL domain was provided that mix the VHs and VLs of SEQ ID NO: 1-8 . The specification discloses only four species (including the humanized) within the instant claim scope. The instant application encompasses (but does not exemplify) fragments and CDRs modification s up to 20% (deletion/addition/substitution) to the claimed VH, VL and VH CDRs and LCDRs of SEQ ID NOs: 1-14 . There is no teaching identifying what amino acids can be varied within the VH-CDRs and/or VL-CDRs antibody regions and still retain antibody or fragments capable of binding MFAP4 . Brown et al (J. Immuno . 1996 May, 3285-91 at 3290 and Tables 1 and 2) describes how a one amino acid change in the VH CDR2 of a particular antibody was tolerated whereas, the antibody lost binding upon introduction of two amino changes in the same region. Vajdos et al. (J. Mol. Biol. 2002, Jul 5, 320(2):415-28 at 416) 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. 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. The scope of the claims encompasses antibodies with VH or VL that encompass variation (addition, deletion, substitution) in their CDRs. The prior art discloses that 6 CDRs as being essential structure of antibody's binding site, and thus when intact, would provide enough structure to define the antibody's binding site (structure/function correlation) e.g., where amino acid substitutions can be made so as to change (e.g. 6CDR's) or retain (e.g., constant or variable framework) antigen binding. Neither the prior art nor applicant's disclosure defines sufficient representative antibodies and/or sufficient structure/function correlation between modifying the VLCDRs or VHCDRs regions of the disclosed antibody and the retention of a specific binding antibody that binds the MFAP4 to satisfy the WD requirement for the claims. Neither the specification, nor the prior art provides any examples to support the premise of mixing and matching VH/VL of different antibodies would result in antigen binding. The prior art does not support a definition of an antibody structure by mixing and matching the VH and VL and result in functional anti- MFAP4 antibody. The specification fails to show that all HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 of the anti- MFAP4 antibodies, AS0326 , HG-HYB 7-14 and HG-HYB 7-5 are equivalent and thus interchangeable . The claim s 20-21, 24, 26 encompass antibodies in which modification of the amino acids may vary in either or both the VH CDRs and/or VL CDRs region of SEQ ID NOs: 1-14 via addition, deletion, substitution or insertion of one or more amino acids. It is unlikely that antibodies or fragments thereof as defined by the claims which may contain less than the full complement of CDRs from the heavy and light chain variable regions of the AS0326 , HG-HYB 7-14 and HG-HYB 7-5 antibody fused to framework sequence, have the required binding function. The specification provides no direction or guidance regarding how to produce antibodies as broadly defined by the claims. Undue experimentation would be required to produce the invention commensurate with the scope of the claims from the written disclosure alone. Further, the specification does not teach that a functional antibody can be obtained by replacing the CDR regions of an acceptor antibody with the less than all the 6 CDRs sequences of a donor antibody. With respect to the recitation an antibody which does not comprise all 6 CDRs of the antibody that is produced by AS0326 , HG-HYB 7-14 and HG-HYB 7-5 , the Examiner directs Applicant's attention to the training material given by Bennett Celsa, Example 2: (Ab genus: modified CDR's) slides 34-40. Example 2 of the Training material (( https://www.aipla.org/docs/default- source/committee-documents/bcp-files/2020/uspto-bcp-antibody-slides-final.pdf?sfvrsn=b377f2cc_0 ) which requires that the claims explicitly recite the binding antigen in addition to all 6 CDR regions for fulfillment of the written description requirements under § 112, 1. Slide 39 indicates that a claim encompasses antibodies with 6 intact CDRs as well as a subgenus of antibodies that encompass up to 10% variation (fragments and/or analogs) in the 6 CDRs lacks written description. Slide 40 provide the conclusion that, a single antibody species would not be deemed by one of skill in the art to be representative of a claim that defines an antibody that binds antigen X comprising at least 90% homology to the 6 CDR of the VH and VL chains. V as-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.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398. Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed. 10 . Claim s 13-32 are rejected under 35 U.S.C. 112 ( a ) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for a method of treating eye fibrosis or liver fibrosis comprising administering anti-MFAP4 antibody m /h AS0326 , ) , HG-HYB 7-14 or HG-HYB 7-5 , does not reasonably provide enablement for the method recited in claims 13-32 . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The claims are directed to the treatment of a broad genus of methods of preventing and treating each and every fibrosis with a genus of anti-MFAP4 antibodies. Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention. The claims are directed to a broad class of antibodies was that the class was defined by its function—the ability to bind to MFAP4 and inhibiting MFAP4-integrin interaction, preventing and treating fibrosis such as liver fibrosis, chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury . However, the specification did not give the skilled in the art enough information to choose candidate antibodies from the millions of options and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.” The specification discloses only 3 species of anti- MFAP4 antibodies, m/hAS0326, ) , HG-HYB 7-14 or HG-HYB 7-5 ; while the claims are directed to a genus of millions of anti- MFAP4 antibodies. In Sanofi- Aventisub , the Federal Circuit relied on its prior precedential opinions when determining whether the full scope of a genus was enabled. These decisions included McRO , Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091 (Fed. Cir. 2020) (hereafter McRO ); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380 (Fed. Cir. 2013) (hereafter Wyeth ); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019) (hereafter Enzo ); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149 (Fed. Cir. 2019) (hereafter Idenix ). The Federal Circuit, citing McRO , provided guidance on the application of enablement to genus claims, holding that “[a] lthough a specification does not need to describe how to make and use every possible variant of the claimed invention, when a range is claimed, there must be reasonable enablement of the scope of the range.” Sanofi- Aventisub , 987 F.3d at 1085 (internal quotations omitted). Additionally, the Federal Circuit characterized Wyeth as holding “that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality.” Id. at 1086. Similarly, the Federal Circuit characterized Enzo as holding “that the specification failed to teach one of skill in the art whether the many embodiments of the broad claims would exhibit that required functionality.” Id. Finally, the Federal Circuit characterized Idenix as affirming “the district court's determination that the claims had both structural and functional limitations, and that undue experimentation would have been required to synthesize and screen the billions of possible compounds because, given a lack of guidance across that full scope, finding functional compounds would be akin to finding a `needle in a haystack.' ” Id. This case is akin to the issue in Sanofi- Aventisub , the court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a `vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. In the instant case, the specification discloses only three species that performed the claimed function by their amino acid sequences, with the claimed genus of millions different anti- MFAP4 antibodies. The instant claims are directed to a class of anti- MFAP4 antibodies that included “a `vast' number of additional antibodies” that the instant specification fails to describe their amino acid sequences. The scope of the instant claims encompassed millions of antibodies and that it was necessary to first generate and then screen each candidate to determine whether it met the functional limitations. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen. The claims simply direct skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the two antibodies they elected to disclose and that “[u] nder Amgen, such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a).” Id. at *8, *10. Amgen attempted to claim an entire class of compounds by their function, namely antibodies that bind to the “sweet spot” of PCSK9 thereby inhibiting it from binding to LDL, while only describing 26 amino acid sequences in its specification. The two processes, the “roadmap” and “conservative substitution” did not save Amgen. According to the Court, these amounted to “little more than two research assignments” which forced scientists to conduct “painstaking experimentation” to see what worked. (citing Incandescent Lamp). The Court therefore held that Amgen’s specification did not enable the claims. At issue is also the treatment of each and every fibrosis in a subject. Example 4 discloses r eversibility of p henotype in p rimary h epatic s tellate c ells u sing a nti-MFAP4 in vitro. The aim of Example 4 is to study effect of treatment with anti-MFAP4 on myofibroblast-like cells from the liver. Example 5 discloses the t reatment of i nduced l iver f ibrosis in r ats with a nti-MFAP4 in vivo. The data demonstrate that treatment of rats having induced liver fibrosis show less Collagen type I after treatment indicating decrease in the formation of fibrous tissue. Example 7 discloses a nti-MFAP4 i nhibits e xperimental c hemically i nduced s tenotic a nastomosis f ormation . [0255] The study showed that anti-MFAP4 injections in small intestinal anastomoses in a porcine model has a positive effect in reducing collagen deposition/fibrosis on postoperative day 28. It further increases the maximal tensile strength. Thus, anti-MFAP4 has a positive effect on the relief of induced stenotic anastomosis in the intestine due to fibrosis arisen as a consequence of surgery. Applicant is claiming that the agonistic anti- MFAP4 antibody can be the magic bullet against all fibrosis . The specification fails to provide empirical data to show that the claimed methods would work in for chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury . On the basis of the disclosed scientific theory, applicant concludes that the scope of the anti- MFAP4 antibody that treat each and every fibrosis encompassed by the claimed invention and be provided as pharmaceutical compositions to treat any fibrosis . The ordinarily skilled artisan would find it unpredictable to distinguish between a general knowledge at the molecular level of conventional anti- MFAP4 antibody which reduce collagen deposition involving many variable competing factors operating in a highly context-dependent manner in vivo. The skilled in the art would find it unpredictable to reducing collagen deposit can have a desirable effect in the context of each and every fibrosis. Kanaan et al ( Matrix Biology. (2022) 111, 1 25 ) provides conflicting data were observed regarding MFAP4 contribution to the process of cardiac remodeling. MFAP4 deficiency reversed aortic banding and isoproterenol-induced cardiac dysfunction, with no effect on cardiac hypertrophy in both models. In addition, a reduction of aortic banding-induced ventricular arrhythmia was observed in MFAP4-deficient mice, explained by the increase of connexin 43, a gap junction protein crucial for the conduction of cardiac electrical signals . In contrast , MFAP4 was more recently suggested to exhibit a protective role in acute and chronic stress-induced cardiac hypertrophy. The presence of MFAP4 was crucial for the regulation of ERK phosphorylation through integrin-related signaling in cardiomyocytes, thus regulating hypertrophic response to stress. On the other hand, no effect of MFAP4 deficiency on local fibrosis development was observed , unlike other studies showing MFAP4 involvement in cardiac fibrosis, as described above. These phenotypic differences in injury-induced cardiac remodeling reported in MFAP4-deficient mice might be related to the difference in the used mice strains as well as to the time course of the respective studies (for cardiac fibrosis analyzed 4 weeks post aortic banding surgery, MFAP4 deficiency had no effect on collagen deposition , whereas for cardiac fibrosis analyzed 8 weeks post-surgery, MFAP4 deficiency reduced collagen deposition). It is also conceivable that MFAP4 is not a primary regulator of cardiac fibrosis and that its loss of function is compensated by other ECM proteins. Taking all these observations together, while the available data provide insight into the importance of MFAP4 in cardiac disease, deepening the understanding of MFAP4 functions at each phase of cardiac remodeling is warranted. Knowing that MFAP4 is abundantly expressed in the heart under homeostatic conditions, it would be of interest to use conditional cell-specific MFAP4 targeting strategies to investigate the respective contribution of MFAP4 expression in distinct cardiac cell types (see page 15, right col., top ¶) . The specification does not provide exemplification of animal model to treat each and every fibrosis claimed in a subject with the claimed anti- MFAP4 antibody. Besides liver fibrosis , the specification does not provide exemplification of animal model to treat each and every fibrosis as claimed . No effect of any therapy was administered to chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury with anti- MFAP4 antibodies. In re Fisher, 166 USPQ 18 indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are drawn to the treatment of chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury with anti- MFAP4 antibodies using the anti- MFAP4 antibodies. Besides treatment of eye (taught by the prior art) and liver fibrosis , no working empirical data demonstrating that the anti- MFAP4 antibodies would be use for the claimed fibrosis conditions. The specification lacks empirical data on the in vivo efficacy of the anti- MFAP4 antibodies on subjects . The experiments in the specification never successfully used the anti- MFAP4 antibody to treat chronic liver diseases, lung fibrosis, eye fibrosis, kidney fibrosis, heart fibrosis, intestinal fibrosis and fibrosis in response to surgery or injury with anti- MFAP4 antibodies . The lack of any working examples is exacerbated because the invention is in a highly unpredictable art- fibrosis - and while the level of skill of in the art may be high, the state of the prior art is that it is in fact unknown and untested what are the underlying molecule and physiologic bases of the therapeutic effects of the anti- MFAP4 antibody in the fibrosis with anti- MFAP4 antibody. The burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to diabetic retinopathy within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed anti- MFAP4 antibody in preventing fibrosis state . Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention. 1 1 . 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. 1 2 . Claims 13 -14, 17- 32 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by WO2019086580 (IDS) . The `580 publication teaches mouse anti-MFAP4 monoclonal antibody (mAS0326) comprises: (a) a light chain variable region (VL) of SEQ ID: 1 (see BGI82912) or SEQ ID:3 containing CDR regions; and (b) a heavy chain variable region (VH) of SEQ ID: 2 or SEQ ID:4 containing CDR regions useful as a medicament for preventing or treating fibrosis of the eye in mammal (see page 3, lines 15+ and page 16, lines 25+ and claim 15 ) including human (see page 17, lines 18-19) , wherein the disorders characterized by pathological neovascularization in the eye is selected from the group consisting of age related macular degeneration (AMD) ( retinal fibrosis ) , including geographic atrophy and proliferative AMD, retinal vein occlusion, retinopathy, hypertensive retinopathy, vitreomacular traction, and diabetic retinopathy (DR) (retinal fibrosis) , including proliferative DR and diabetic macular edema. . The `580 publication teaches a composition comprising the antibody and one or more physiologically acceptable carriers, excipients and/or diluents (see published claim 13), wherein the ligand is a polyclonal antibody, a monoclonal antibody, an antibody, wherein the heavy chain and the light chain are connected by a flexible linker, an Fv molecule, an antigen binding fragment, a Fab fragment, a Fab' fragment, a F(ab')2 molecule, a fully human antibody, a humanized antibody, and a chimeric antibody (published claim 4) . Figure 1 shows alignment of variable heavy chain (HC) and light chain (LC) sequences for monoclonal antibodies HG Hyb 7-1 (HYB7-1)(LC=SEQ ID NO: 5 and HC=SEQ ID NO : 6), HG Hyb 7-5 (HYB7-5) (LC=SEQ ID NO : 7 and HC=SEQ ID NO : 8), mAS0326 (LC=SEQ ID NO : 1 and HC=SEQ ID NO: 2) and hAS0326 (LC=SEQ ID NO: 3 and HC=SEQ ID NO: 4). CDR sequences are indicated by underlining. The `580 publication teaches the ligand or composition can be administered by different route including intravenously to the eye, ocularly or subcutaneously (see page 18, lines 7+). Alignment of claimed SEQ ID NOs: 9-10-11 with referenced SEQ ID NO: 1 , 3. Qy 1 RASKSISKYLA---------------SGSTLQS--------------------------- 18 ||||||||||| ||||||| Db 24 RASKSISK Y LAWYQERPGKTNKLLIYSGSTLQSGIPSRFSGSGSGTDFTLTISSLEPEDF 83 Qy 19 -----QQHNEYPFTF 28 |||||||||| Db 84 AMYYCQQHNE Y PFTF 98 Alignment of claimed SEQ ID NOs: 12-13-14 with referenced SEQ ID NO: 2, 4. Qy 1 SYWMHW-------------VIHPNSGNTKYNEKFRS------------------------ 23 |||||| ||||||||||||||||| Db 31 S Y WMHWVRQARGQRLEWIGVIHPNSGNTKYNEKFRSRVTMTTDTSTSTAYMELRSLRSDD 90 Qy 24 --------EMWNYGNSWYFDV 36 ||||||||||||| Db 91 TAVYYCAR E MWNYGNS W YFDV 111 The reference teachings anticipate the claimed invention. 1 3 . Claims 13-32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CrossingBio ( 25th Jun 2019 ) . CrossingBio teaches novel therapeutic anti-MFAP4 antibody therapy for fibrotic conditions in development. Novel first-in-class anti-MFAP4 antibody for treatment of fibrosis associated with diseases of the liver, kidney and retinal/eye and surgery . CrossingBio teaches t he novel therapeutic target is MFAP4 (Microfibrillar Associated Protein 4), a protein implicated in fibrosis: (a) MFAP4 is a novel TGF-beta effector protein , (b) Localized in the extracellular matrix , (c) Highly upregulated during fibrosis by activated myofibroblasts . CrossingBio’s pipelin e techology ( i ) a nti-MFAP4 antibody combination therapy with GLP-1 agonist for liver fibrosis (MASH w. moderate to advanced liver fibrosis; stage 2 or 3) (ii) anti-MFAP4 antibody combination therapy with GLP-1 agonist for kidney fibrosis (iii) anti-MFAP4 antibody combination therapy with VEGF antagonist for retinopathy (inhibition of vascular leakage, angiogenesis and fibrosis ) . CrossingBio teaches that highly MFAP4 is upregulated during fibrosis ( Figure 1 ) . T he research team have developed a novel and first in class MFAP4 blocking antibody ( Figure 2 ) such as hAS0323 ( humanized and comprising the claimed SEQ ID NOs) which is efficiently blocks the interaction between MFAP4 and integrins associated with progression of the fibrosis process (αv-integrins that bind to the RGD-motif of MFAP4. Data and findings supporting the liver program: Figure 3 shows serum MFAP4 is a liver fibrosis biomarker , Figure 4 which shows that MFAP4 expression in alcohol-induced liver fibrosis is cell type specific. Also shows that MFAP4 overexpression in hepatic stellate cell cluster , Figure 5 , Figure 6 which shows th e IV administration of anti-MFAP4 reduces fibrosis in both rat and mouse model of liver fibrosis in vivo , Figure 7 which shows that anti-MFAP4 blocks the MFAP-induced collagen synthesis in hepatic satellite cell -derived myofibroblasts in vitro and decreases fibrosis markers include collagen in rat liver fibrosis model in vivo . Data and findings supporting the kidney program: Figure 8 , Figure 9 , Figure 10 , Figure 11 . CrossingBio provides d ata and findings supporting the retinal/eye program: Figure 13 , Figure 14 , Figure 15 , Figure 16 shows the intravitreal demonstration of anti-MF AP4 antibody in non-human primate eye using DLAAA-model , Figure 17 shows that macular proteome supports MFA94 antibody-mediated reduction of retinal fibrosis . The reference teachings anticipate the claimed invention. 14 . Claims 13- 16, 19 , 27-32 are rejected under 35 U.S.C. 102(a)( 2 ) as being anticipated by WO 2022025827 . The `827 publication teaches method s of treating or preventing a disease associated with fibrosis, comprising inhibiting MFAP4 (published claim 1) , method s of treating or preventing a disease associated with fibrosis, comprising administering a therapeutically or prophylactically effective amount of an inhibitor of MFAP4 to a subject (see published claim 2) such as a mammalian subject , such as a human subject , wherein the disease is a liver disease or condition (published claim 5), wherein the liver disease or condition is selected from: acute liver disease, chronic liver disease, metabolic liver disease, steatosis, liver fibrosis, primary sclerosing cholangitis (PSC ), cirrhosis, mild liver fibrosis, advanced liver fibrosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic fatty liver disease (ALFD), alcohol-related liver disease (ARLD), hepatic ischemia reperfusion injury, primary biliary cirrhosis (PBC), hepatitis, liver damage, liver injury, liver failure, metabolic syndrome, obesity, diabetes mellitus, end-stage liver disease, inflammation of the liver, lobular inflammation, and/or hepatocellular carcinoma (HCC) (published claim 6), wherein the inhibitor is antibody (published claim 7) , wherein the i nhibitor is an antibody that is capable of binding to MFAP4 including PA5-42013 ( i.e., polyclonal ) or ab169757 ( monoclonal ) . The `827 publication further teaches that t he compositions may be prepared for topical, parenteral, systemic, intracavitary, intravenous, intraarterial, intramuscular, intrathecal, intraocular, intravitreal, intraconjunctival , subretinal, suprachoroidal, subcutaneous, intradermal, intrathecal, oral, nasal or transdermal routes of administration which may include injection or infusion. The reference teachings anticipate the claimed invention. 1 5 . 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. 1 6 . Claims 13-32 are rejected under 35 U.S.C. 103 as being unpatentable over WO2019086580 (IDS) in view of WO 2022025827 . The teachings of the `580 and `827 publication have been discussed, supra. The reference teachings differ from the claimed invention only in the recitation that the fibrosis is liver fibrosis or chronic liver diseases in claim 15 and the liver diseases is cirrhosis in claim 16. Those of skilled in the art would have had a reason to substitute the anti-MFAP4 antibodies taught by the `580 publication for the anti-MFAP4 antibodies taught by the `827 publication because like the anti-MFAP4 antibodies taught in the `827 publication, hAS0326 , m AS0326 , HG Hyb 7-5 and HG Hyb 7- 1 treat fibrosis. Substituting a known element for another, to yield the known result, is obvious. See KSR, 550 U.S. at 416, 421 (2007). "[W]hen a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result." KSR Int'l v. Teleflex Inc., 550 U.S. 398,416 (2007). "Structural similarity, alone, may be sufficient to give rise to an expectation that compounds similar in structure will have similar properties." In re Merck & Co., Inc., 231 USPQ 375,379. From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary. 1 7 . The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action