DETAILED ACTION
Election/Restrictions
Applicant’s election of Group I, claims 1-13, and the Species Antibody IVA: Heavy chain: SEQ ID NO: 71 and Light chain: SEQ ID NO: 75; H chain CDR1-CDR3 SEQ ID NOS: 72-74 and L chain CDR1-3 SEQ ID NOS: 76-78), in the reply filed on 11/11/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 14-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-3, 4 part (IVA), 5 (IVB) and 80% (IVC), 6(IVC), 7(IVB) & (IVC), 8(IVB) and (IVC), 9 (IVB) & (IVC), 10 (at least 80% To (IVB)and (IVC), 11 (IVB/IVC with subs/del/insrt/addn), 12 and 13 read on the elected Invention and species.
Claim Rejections - 35 USC § 112-2nd paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is vague and indefinite because it the mere recitation of a name, i.e., an isolated monoclonal antibody or derivate thereof that specifically binds to corisin, to describe the invention is not sufficient to satisfy the Statute's requirement of adequately describing and setting forth the inventive concept. The claim should provide any structural properties, such as the amino acid sequence of the antibody, which would allow for one to identify the antibody without ambiguity. The mere recitation of a name of the protein the claimed antibody binds does not allow for one to identify the protein without ambiguity. Appropriate clarification and/or correction is required.
Claims 1-14 are vague and indefinite because it is unclear what structure(s) are encompassed by the term “derivative thereof”. The term “derived” does not provide the structural character or properties from the source that are to be retained in the final product. The phrase “derived from” should be changed to “isolated from”. Appropriate clarification and/or correction is required.
Claim 3 is vague and confusing because it recites “wherein PESSGNP (SEQ ID NO: 68) or NPAGY (SEQ ID NO: 69) is an epitope” and it is unclear what this is in reference to. The claim does not recite that the antibody of claim 1 binds to these epitopes and there is no mention if these are epitopes of the corisin protein in claim 1. Accordingly, their relation to claim 1 is confusing.” Appropriate clarification and/or correction is required.
Claims 1-13 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of antibodies IA-IVA is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: these antibodies have completely different amino acid sequences and bind different epitopes (their use is different based on different binding capacities). These are not mere species of one another. They are different antibodies with different amino acid sequences.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Objections
Claims 1-13 are objected to because of the following informalities: they contain non-elected species, e.g., different antibodies which were not elected. Note: these are rejected under improper Markush grouping above. Appropriate correction is required.
Claim Rejections - 35 USC § 112-Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-13 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:
An isolated monoclonal antibody comprising a heavy chain with the amino acid sequence set forth in SEQ ID NO: 71 and a light chain comprising the amino acid set forth in SEQ ID NO: 75; and
An isolated monoclonal antibody comprising an H chain variable region comprising CDR1 amino acid SEQ ID NO: 72, CDR2 amino acid SEQ ID NO: 72 and CDR3 SEQ ID NO: 74 and a light chain variable region comprising a CDR1 amino acid SEQ ID NO: 76, CDR2 amino acid SEQ ID NO: 77 and CDR3 SEQ ID NO: 78.
, does not reasonably provide enablement for the scope of the instant claims which includes variants with at least 80% identity to the recited amino acid sequences and antibodies with only a heavy chain or only a light chain, and derivatives with no disclosed sequence wherein the variants neutralize and/or inhibit corisin-induced apoptosis. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
NOTE: claim 4 and 9 are include the enabled scope, e.g., -the elected IVA with H chain CDR1-CDR3 SEQ ID NOS: 72-74 and L chain CDR1-3 SEQ ID NOS: 76-78) and claim 9 recites the elected IVB and IVC (L chain SEQ ID 75 and H chain SEQ ID 71); however, the claims also recite “or a derivative thereof” which is not enabled as outlined in the following paragraphs.
Claims 1-3, 5, 6 and 12-13 define only parts of the claimed antibodies. None of these definitions relates to a specific combination of complete light and heavy variable regions which would define an antibody’s entire binding site. Only such fully defined binding domain including all six CDRS as well as frame work sequences would confer a specific property on said antibody. The specification is not enabled for the instant claims which do not fully define the antibody which is claimed. It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations 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. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required inorder to form functional antigen binding sites. Even minor changes in the aminoacid sequences of the heavy and light variable regions, particularly in the CDRs,may dramatically affect antigen-binding function.
Claims 7, 8 and 10 include antibodies with variant sequences of at least “80% identical the defined heavy and light chains and claim 11 allows for variant antibodies with any substation, deletion, insertion, or addition of one or several amino acid residues in comparison to the sequences of SEQ ID NO: 71 and 75. Claims 1-13 also recite “any derivatives thereof” with no description of the structure of the ‘derived’ antibody.
The specification states that substitutions, additions, or deletions, may be made to the defined sequences; however, the specification provides no guidance as to what the amino acids may be changed without causing a detrimental effect to the antibodies and with the added features of being able to neutralize and/or inhibit corisin-induced apoptosis in claim 13. It is unpredictable as to which amino acids could be removed and which could be added. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein’s sequence where amino acid substitutions can be made with a reasonable expectation of success are limited. Other positions are critical to the protein’s structure/function relationship, e.g., such as various positions or regions directly involved in binding, catalysis in providing the correct three-dimensional spatial orientation of binding and catalytic sites. These regions can tolerate only very little or no substitutions. Selective point mutation to one key residue could eliminate the function of the polypeptide. It could eliminate its functional properties. If the range of decreased binding ability after single point mutation of a protein antigen varies, one could expect point mutations in the protein antigen to cause varying degrees of loss of protection/function, depending on the relative importance to the binding interaction of the altered residue. Alternatively, the combined effects of multiple changes, as instantly claimed, in an antigenic determinant could again result in loss of function. A protein having multiple antigenic sites, multiple point mutations, or accumulated point mutations at key residues could create a new antigen that is precipitously or progressively unrecognizable by any of the antibodies in the polyclonal pool. As stated above, Applicants have not shown the particular substitution and the result it produces. Applicants have provided no guidance to enable one of ordinary skill in the art how to determine, without undue experimentation, the effects of different amino substitutions and the nature and extent of the changes that can be made. It is expensive and time consuming to make amino acid substitutions at more than one position, in a particular region of the protein, in view of the many fold possibilities for change in structure and the uncertainty as to what utility will be possessed. The three-dimensional structure of molecules is important for their biological function and even a single amino acid difference may account for markedly different biological activities. Amino acids owe their ‘significance’ to their inclusion in a pattern which is directly involved in recognition by, and binding to, the receptor and the significance of the particular amino acids and sequences for different amino acids cannot be predicted a priori, but must be determined from case to case by painstaking experimental study. The instant claims allow for substitutions with amino acids of vastly different properties and they do not recite the specific changes in the claims. Although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations.
As one can see from the prior art in the sequence alignment found in public PAIR, antibodies with at least 80% identity encompass antibodies that are vastly different structurally and functionally. For example:
SEQ ID NO: 71
Leroyer et al EP3629024-A1. April 1, 2020. Teaches Anti-sCD146 2B9-4 monoclonal heavy chain variable region, SEQ ID 99. Accession No. BHN83493; CD146; MUC18; heavy chain variable region; monoclonal antibody. 83.5% similarity to SEQ ID NO: 71.
Barbour et al WO2015155694-A1.10/15/15; SEQ ID NO: 62; 81.8% similarity; brain effector entity which comprises an antibody.
Roed et al WO2019243502-A1. 12/26/19 antibodies to GLP-1 analog/anti-TfR-Fab heavy chain fusion protein SEQ 10. 81.8% identity similarity to SEQ ID NO: 71.
Hanzation et al WO2014089209-A2. 6/12/14 Bispecific antibody VH (DVD1294H/DVD2669H), SEQ 60. 81.8% homology. similarity to SEQ ID NO: 71.
Kaluza et al Us Patent No. 9493553; Sequence 56; ANTI-alpha-SYNUCLEIN ANTIBODIES 81.8% similarity to SEQ ID NO: 71.
SEQ ID NO: 75
Benatuil et al WO2017214456-A1. 12/14/17 Anti-CD98 Ab6 antibody light chain variable region SEQ: 32. AC BES24813; 92.9% similarity to SEQ ID NO: 75.
Mizuno et al WO2016006241-A1. 1/14/16 Anti-PD-1 mab light chain variable region (VL) 4F12-E6, SEQ ID 5. 92.9% similarity to SEQ ID NO: 75.
Schaer, DA. WO2017091429-A1. 6/1/17 Anti-PD-L1 antibody light chain (LC) 178G7, SEQ ID 12. AC BDY43600; 92.4% similarity to SEQ ID NO: 75.
Bitter et al WO2016164731-A2. 10/13/16 Humanized CD20 CAR light chain variable domain, SEQ:987. AC BDH61671; 92% similarity to SEQ ID NO: 75.
Ogrunc et al US Pat 11,723,926 Sequence 203, US/17032510 Patent No. 11723926 Sequence 203; 92% similarity to SEQ ID NO: 75.
US Patent No. 10280223; SEQ ID NO: 5; Antibody against canine PD-1 or canine PD-L1. 92.4% similarity to SEQ ID NO: 75.
Further, Ferrara et al (Mabs. Feb. 2015. 7(1): 32-41) show the diversity of antibody structures that can bind to the same antigen. Per page 36, initial antibody library has a diversity of over 3 x 10^11. Antibodies that have some reactivity to the antigen are on the order of 10^5 to 10^6. They then screened these further. “The diversity of these polyclonals was also assessed by deep sequencing. Table 3 shows the analysis of the polyclonals at the highest stringency parameters. The number of unique HCDR3s range from 74 to 460 for the 6 polyclonals we analyzed.” (pg 35). “The number of different HCDR3s selected against the test antigens ranges from 74 to 460 (Table 3), with the actual number of different antibodies likely to be significantly higher when different VL chains and additional VH mutations are taken into account” (pg 36). Also, on the first page it mentions that the ERBB2 [aka HER2/Neu] protein has over 1,200 commercially available antibodies. It doesn’t specify whether these all have different CDRs or not.
Edwards et al (J. Mol. Biol. 2003. 334: 103-118) teaches that over one thousand different antibodies, all different amino acid sequences, can be found that bind to a single protein. See abstract. Moreover, a high level of sequence diversity was observed in the VH CDR3 domains of these antibodies, with 568 different amino acid sequences identified. Only about 40% of these antibodies inhibited binding to the specific protein, BLys. Lloyd et al (Protein Engineering, Design and Selection. 2009. 22(3): 159-168) teach that over 5000 target-specific antibodies were isolated to 28 antigens and only 3340 modulate the biological function of the target antigen. See abstract. These references show the unpredictability of identifying therapeutic antibodies and specific structures.
Pascalis et al. The Journal of Immunology (2002) 169, 3076-3084 demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (2003) BBRC 307, 198-205, which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.).
The references demonstrate that an antibody must comprise all 6 CDRs inorder to maintain the antigen binding specificity and affinity which is characteristicof the immunoglobulin and that thousands of potential antibodies with different amino acids structures against a single antibody may be found and many will not have therapeutic value. Single VH or VL polypeptides would not bind antigen.
Additionally, The Office notes that the issue is make and use, not make and test to see if the skilled artisan could use. In short, the instant application encompasses a plethora of antibody variants possessing the ability to bind LF/LFIOE, and identifies some broad categories that might work, however, these descriptions, without more precise guidelines, amount to little more than "a starting point, a direction for further research." Genentech, 108 F.3d at 1366. See also Calgene, 188 F.3d at 1374 ("the teachings set forth in the specification provide no more than a 'plan' or 'invitation' for those of skill in the art to experiment practicing [the claimed invention]; they do not provide sufficient guidance or specificity as to how to execute that plan"); National Recovery Technologies, 166 F.3d at 1198 (stating that patent-in-suit "recognizes a specific need.., and suggests a theoretical answer to that need. It provides a starting point from which one of skill in the art can perform further research in order to practice the claimed invention, but this is not adequate to constitute enablement").
The instant specification does not describe the claimed invention in terms that will "enable any person skilled in the art.., to make and use" the invention commensurate in scope with the claims. At most, the specification will enable a person of ordinary skill in the art to attempt to discover how to practice the claimed invention.
Claim Rejections - 35 USC § 112-Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to, for example:
An isolated monoclonal antibody molecule or a derivative thereof that specifically binds to corisin.
Claims also include variants with at least 80% identity to the recited amino acid sequences and antibodies with only a heavy chain or only a light chain, and derivatives with no disclosed sequence wherein the variants neutralize and/or inhibit corisin-induced apoptosis.
To fulfill the written description requirements set forth under 35 USC § 112, first paragraph, the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession the claimed invention. Applicants have not described the genus of claimed antibodies such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the claimed invention at the time the application was filed.
The purpose of the "written description" requirement is broader than tomerely explain how to "make and use"; the applicant must convey with reasonableclarity to those skilled in the art that, as of the filing date sought, he or she was inpossession of the invention. The invention is, for purposes of the "writtendescription" inquiry, whatever is now claimed. See Vas-Cath, Inc. v. Mahurkar,935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).Furthermore, the written description provision of 35 USC § 112 is severable fromits enablement provision; and adequate written description requires more than amere statement that it is part of the invention and reference to a potential methodfor isolating it. The nucleic acid itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Possession may be shown in a variety of ways including description of an actualreduction to practice, or by showing the invention was 'ready for patenting' such asby disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See MPEP 2163.20. Accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus. Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of fragments or variants, the skilled artisan could not immediately recognize that Applicants were in possession of the claimed genus of antibodies and fragments at the time of filing.
Ferrara et al (Mabs. February 2015. 7(1): 32-41) discusses polyclonal diversity but the logic can be extended to the diversity of potential monoclonal antibody structures. These were generated by a technique combining phage and yeast display but it gives some idea of the diversity of antibody structures that can bind to the same antigen. Per page 36, initial antibody library has a diversity of over 3 x 10^11. Antibodies that have some reactivity to the antigen are on the order of 10^5 to 10^6. They then screened these further. “The diversity of these polyclonal antibodies was also assessed by deep sequencing. Table 3 shows the analysis of the polyclonals at the highest stringency parameters. The number of unique HCDR3s range from 74 to 460 for the 6 polyclonals we analyzed.” See page 35. “The number of different HCDR3s selected against the test antigens ranges from 74 to 460 (Table 3), with the actual number of different antibodies likely to be significantly higher when different VL chains and additional VH mutations are taken into account” (pg 36). Also, on the first page it mentions that the ERBB2 [aka HER2/Neu] protein has over 1,200 commercially available antibodies. It doesn’t specify whether these all have different CDRs or not.
The scope of the claim includes numerous structural variants (i.e. derivatives and antibodies with substitutions, insertions, deletions, etc.), and the genus is highly variant because a significant number of structural differences between genus members is permitted. The specification does not describe any members of the claimed genus by complete structure. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the claimed genus. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
Edwards et al (J. Mol. Biol. 2003. 334: 103-118) teaches that over one thousand different antibodies, all different amino acid sequences, can be found that bind to a single protein. See abstract. Moreover, a high level of sequence diversity was observed in the VH CDR3 domains of these antibodies, with 568 different amino acid sequences identified. Only about 40% of these antibodies inhibited binding to the specific protein, BLys. Lloyd et al (Protein Engineering, Design and Selection. 2009. 22(3): 1`59-168) teach that over 5000 target-specific antibodies were isolated to 28 antigens and only 3340 modulate the biological function of the target antigen. See abstract. These references show the unpredictability of identifying therapeutic antibodies and specific structures.
There are no drawings or structural formulas disclosed of any of thesefragments or variants of the claimed antibodies. There is no teaching in thespecification regarding which 20% of the structure can be varied and still produce a antibody with the recited function. Although the disclosure of the SEQ IDs combined with the knowledge in the art, may put one in possession of peptides that are at least 20% identical, the level of skill and knowledge in the art is such that one of ordinary skill would not be able to identify without further testing which of those antibodies and/or antibody fragments could effectively work in the claimed method. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genus of antibodies.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over D’Alessendro-Gabazza et al (Nat. Commun., 2020, 11:1539; pages 1-17; provided by Applicants) in view of Breedveld, F (The Lancet. February 2000. 355: 735-740).
D’Alessendro-Gabazza teaches that Staphylococcus pro-apoptotic peptide induces acute exacerbation of pulmonary fibrosis. See abstract, page 6, right column, line 9 to page 7, left column, line 8, page 7, left column, lines 37-49, page 13, left column, lines 56-61. D’Alessendro-Gabazza et al indicates that apoptosis of lung epithelial cells contributes to the progression of idiopathic pulmonary fibrosis (abstract), that Staphylococcus nepalensis releases a peptide having been named corisin and induces apoptosis of lung epithelial cells (abstract), that the amino acid sequence of corisin is IVMPESSGNPNAVNPAGYR (page 6, right column, line 9 to page 7, left column, line 8), e.g, which is the same amino acid sequence set forth in Applicants’ SEQ ID NO: 1).
However, D’Alessendro-Gabazza is different from instant claim 1 of the present application since a monoclonal antibody against corisin is not produced.
D’Alessendro-Gabazza does indicate that a polyclonal antibody against corisin is useful for the detection of corisin and the suppression of apoptosis caused by corisin, and also indicates that corisin can serve as a diagnostic marker and a therapeutic target. They teach that a polyclonal antibody against corisin was produced and said antibody could be used for the detection of corisin and the inhibition of apoptosis inducement by corisin (page 7, left column, lines 37-49), and that corisin is a novel diagnostic marker and a therapeutic target of idiopathic pulmonary fibrosis (page 13, left column, lines 56-61).
Since a useful polyclonal antibody against corisin is known, a person skilled in the art would easily have been motivated to obtain a monoclonal antibody that is useful for diagnosis and therapy, using the same immunogen.
Breedveld teaches that the therapeutic potential of monoclonal antibodies was quickly realized after the hybridoma technique allowed their development in the mid 1970s. Because of their immortal nature, hybridoma cells can be frozen, thawed, and recultured in vitro. As a result, for a given monoclonal line, there exists a constant and renewable source of antibodies for study. Breedveld teaches that the therapeutic use of mAbs is now well established. They teach that, by contrast with polyclonal antibodies, mAbs are monospecific and homogeneous which makes them effective tools in the development of therapies and diagnostics. See column 1, page 735. It is taught that chimeric humanized and fully humanized mAbs can now be made by recombinant engineering. See column 1, second paragraph, page 735.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made that monoclonal antibodies which specifically bind the corisin could be produced and used in lieu of the polyclonal antibodies taught by D’Alessandro-Gabazza because Breeveld teaches that by contrast with polyclonal antibodies, mAbs are monospecific and homogeneous which makes them effective tools in the development of therapies and diagnostics. See column 1, page 735. Additionally, Breeveld teaches that chimeric humanized and fully humanized mAbs can now be made by recombinant engineering. See column 1, second paragraph, page 735. One of ordinary skill in the art would have been motivated to produce monoclonal antibodies to corisin because D’Alessandro-Gabazzo specifically teach that antibody could be used for the detection of corisin and the inhibition of apoptosis inducement by corisin (page 7, left column, lines 37-49), and that corisin is a novel diagnostic marker and a therapeutic target of idiopathic pulmonary fibrosis (page 13, left column, lines 56-61). One of ordinary skill in the art would have been motivated to make monoclonal antibodies because of their immortal nature, hybridoma cells can be frozen, thawed, and recultured in vitro. As a result, for a given monoclonal line, there exists a constant and renewable source of antibodies for study. D’Alessandro-Gabazzo specifically that the amino acid sequence of corisin is IVMPESSGNPNAVNPAGYR (page 6, right column, line 9 to page 7, left column, line 8), e.g, which is the same amino acid sequence set forth in Applicants’ SEQ ID NO: 1). Accordingly, the corisin contains the antibodies recited in instant claim 3. The dependent claims contain variants and derivative antibodies thereof, as well as mutants with insertions, deletions and substitutions, etc. so the dependent claims which are not the exact Species Antibody IVA: Heavy chain: SEQ ID NO: 71 and Light chain: SEQ ID NO: 75; H chain CDR1-CDR3 SEQ ID NOS: 72-74 and L chain CDR1-3 SEQ ID NOS: 76-78), but derivatives or variants thereof in claims 1-13 are encompassed by the prior art cited above.
Prior art not presently relied upon:
Introducing an amino acid mutation into a toxic peptide to detoxify same and using same as a vaccine is a well-known feature in the relevant technical field (document 2, paragraphs [0012]-[0023] and [0030]; document 3, abstract; document 4, page 7, lines 4-13), and it is not considered to be particularly difficult at all to apply such well-known feature to the corisin peptide described in document 1.
Document 2: JP 2005-247868 A (CHIRON SRL) 15 September 2005 (2005-09-15), paragraphs [0012]-[0023], [0030] & US 2003/0170262 A1, paragraphs [0013]-[0024], [0031]
Document 3: FONTANA MLR. et al. Construction of nontoxic derivatives of cholera toxin and characterization of the immunological response against the A subunit. Infect. Immun., 1995, vol. 63, no. 6, pp. 2356-2360, abstract
Document 4: WO 2020/157222 Al (CEVA SANTE ANIMALE S.A.) 06 August 2020 (2020-08-06), page 7, lines 4-13 & EP 3689373 Al
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
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/JENNIFER E GRASER/ Primary Examiner, Art Unit 1645 12/10/25