Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claims 1-9 are under consideration.
Priority
This application claims the benefit of and priority to U.S. Application Serial No.
63/613,636, filed 12/21/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/02/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 3 and 7 are objected to because of the following informalities:
Claim 3: For consistency with the other claims, remove the comma after “53”.
Claim 7: Claim 7 recites “effective amount of at least one antibody of claim 1”. Change to “effective amount of the antibody of claim 1”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9 is 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.
See claims 1-9 as submitted 12/23/2024.
Instant claim 1 recites: An antibody comprising: a variable heavy chain (VH) comprising SEQ ID NO: 11 or a sequence having at least 90% identity thereto; and a variable light chain (VL) comprising SEQ ID NO: 12 or a sequence having at least 90% identity thereto; wherein the antibody comprises at least one mutation at a position selected from: position 77 relative to SEQ ID NO: 11; position 53 relative to SEQ ID NO: 12; position 70 relative to SEQ ID NO: 12; and position 71 relative to SEQ ID NO: 12.
Instant claim 2 recites: The antibody of claim 1, wherein the VH comprises a lysine, an asparagine, or a cysteine at position 77 relative to SEQ ID NO: 11.
Instant claim 3 recites: The antibody of claim 1, wherein the VL comprises a serine, an alanine, a glutamine, or a glycine at position 53, relative to SEQ ID NO: 12.
Instant claim 4 recites: The antibody of claim 1, wherein the VL comprises an asparagine, or an alanine at position 70 relative to SEQ ID NO: 12.
Instant claim 5 recites: The antibody of claim 1, wherein the VL comprises a cysteine at position 71 relative to SEQ ID NO: 12.
Instant claim 6 recites: The antibody of claim 1, wherein the VH comprises SEQ ID NO: 1, 2, 3, 11 or a sequence having at least 90% identity thereto; and wherein the VL comprises SEQ ID NO: 4, 5, 6, 7, 8, 9, 10, 12 or a sequence having at least 90% identity thereto.
Claims 7 is dependent on claim 1, claim 8 is dependent on claim 7, and claim 9 is dependent on claim 8.
Although SEQ ID NO: 11 and SEQ ID NO: 12 are provided for both the variable heavy chain and the variable light chain, claims 1 and 6 also recite “at least 90% identity thereto” and in claim 1, the additionally broad statement, “at least one mutation at a position selected from…”. Claims 2-5, dependent on claim 1, do provide some degree of limitation with several specific antibody amino acid residue mutations identified. But even so, these recitations still suggest a rather broad genus. And as such, the specification does not appear to provide sufficient support for all of the possibilities of antibodies within this genus whether in basic characterization or more importantly, in antibody binding ability. Without evidence of binding ability, it would be difficult for one skilled in the art to envision the role of the antibody within a pharmaceutical composition (as recited in claim 7), as part of a method for treating coronavirus disease (as recited in claim 8) caused by a SARS-CoV-2 Delta variant (as recited in claim 9).
The following quotation from section 2163 of the Manual of Patent Examination
Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
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 claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. 'A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
The specification defines the terms antibody, antibody molecules, antibody fragments and antibody-derived fragments [0043 and 0044]. The specification also teaches fragments may comprise a heavy chain variable region (VH domain) and light chain variable region (VL). Fragments may comprise one or more of the heavy chain complementarity determining regions (CDRHs) of the antibodies or of the VH domains, and one or more of the light chain complementarity determining regions (CDRLs), or VL domains to form the antigen binding site. The specification further teaches generalities of CDRs as known in the art (p. 7-8).
The specification/drawings show different experiments with 9 redesigned IgGs for virus neutralization, which is supportive of the Applicant having those antibodies/variants in their possession, the specification is not all inclusive for other conceivable possibilities. The 9 IgGs include 001/002, 011/012, 019/020, 025/026, 031/032, 088/089, 106/107, 108/109, and 118/119. SEQ ID NO: 11 refers to heavy chain L106 while SEQ ID NO: 12 refers to light chain L107 (p. 33). The specification also teaches in FIG. 6B. SARS-CoV-2 virus neutralization for Delta variant mutated anti-RBD antibodies at increasing antibody concentrations (p. 4, [0026]. With respect to the 106/107 antibody, CDR3 segments and their sequences on the heavy and the light chains are identified on p. 33.
It is known in the art that even the most minor differences can have significant effects on antigen-antibody binding ability. The art relating to antibodies recognizes 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 that 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 in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. ("Single amino acid substitution altering antigen-binding specificity," Proc Natl Acad Sci USA 79:1979-1983 (1982)(See 892-Notice of References Cited). Rudikoff et al. teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (p. 1979.
Further, Goel et al. (“Plasticity within the Antigen-Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response,” J. Immunol. 173: 7358-7367 (2004))(See PTO-892: Notice of References Cited) teaches antibodies that bind to the same 12-mer but have very different CDRs; Lloyd et al. (“Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens,” Protein Engineering, Design & Selection, Vol. 22, No. 3: 159-168 (2009))(See PTO-892: Notice of References Cited) teaches: on average, about 120 different antibodies in a library can bind to a given antigen; Edwards et al. (“The Remarkable Flexibility of The Human Antibody Repertoire; Isolation of Over One Thousand Different Antibodies to a Single Protein, BLys,” J. Mol. Biol. 334: 103-118 (2003))(See PTO-892: Notice of References Cited) teaches: a library contained over 1000 antibodies that bound to a single 51kDA protein, including unique VH and 705 VL sequences; there were 568 different CDR3 regions.
Given the highly diverse nature of antibodies, particularly in the CDRs, one of ordinary skill in the art generally cannot envision the structure of an antibody by knowing its binding characteristics (for example, binding to the receptor-binding domain (RBD) of SARS-CoV-2).
Therefore, in light of the knowledge in the art, the broad scope of the claim (at least 90% identity of both VH and VL (as recited in claims 1, 6) as well as the at least one mutation as provided in claim 1), and the teachings in the specification, there is still a high level of uncertainty as to which antibodies fall within the scope of the indicated genus, particularly without six well-defined CDRs within the claims or the specification.
In view of breadth of the claim, it is asserted that one of ordinary skill in the art cannot immediately envision what other antibodies within the scope of the claims can compete for binding to a coronavirus, such the SARS-CoV-2 Delta variant.
For the reasons above, the application has not provided sufficient written description support for the use of the genus of antibodies and their use as identified in claims 1-9.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Considering claim 6’s dependency on claim 1, the claim appears to broaden the sequence identity. For example, SEQ ID NO: 1 has a 99.6% Query Match to SEQ ID NO: 11. So, a sequence having at least 90% identity to SEQ ID NO: 1 would broaden the claim to a sequence with a 89.6% identity. Similarly, and as another example, SEQ ID NO: 4 has a 99.3% Query Match to SEQ ID NO: 12. So, again, a sequence having at least 90% identity to SEQ ID NO: 4 would also broaden the claim to a sequence with a 89.3% identity.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1, 6, 7, 8, 9 are rejected under 35 U.S.C. 103 as being unpatentable over Kreye et al. (Kreye)(WO2021239949A1)(See PTO-892 Notice of References Cited) as evidenced by Mlcochova et al (Mlcochova)(See PTO-892 Notice of References Cited).
See claims 1, 6, 7, 8, 9 as submitted 12/23/2024.
Regarding claims 1 and 6, Kreye teaches:
“In one embodiment, the antibody or antibody fragment of the invention comprises: a heavy chain variable (VH) domain, said VH domain comprising a sequence of at least 70%, preferably at least 80% or at least 90%, or more preferably at least 95% sequence identity to one of SEQ ID NO 16, 24, 32, 40, 48, 56, 64, 72, 80, 88, 96, 104, 112, 120, 128, 136, 144, 152 or 160, and a light chain variable (VL) domain, said VL domain comprising a sequence of at least 70%, preferably at least 80% or at least 90%, or more preferably at least 95% sequence identity to one of SEQ ID NO 17, 25, 33, 41 , 49, 57, 65, 73, 81 , 89, 97, 105, 113, 121 , 129, 137, 145, 153 or 161”(p. 16, and reference claim 10).
Kreye teaches “Anti-spike monoclonal antibody CV38-221 IgG HC, SEQ ID 136” with a 96.8% Query Match to SEQ ID NO: 11 with a tyrosine (Y) at position 77 relative to SEQ ID NO: 11 rather than a phenylalanine (F) (see Result #5, BKJ13278, us-19-000-508-11.rag, 09/02/2026, in supplemental contents tab)(reads on a VH comprising SEQ ID NO: 11 or a sequence having at least 90% identity thereto; and wherein the antibody comprises at least one mutation at a position selected from: position 77 relative to SEQ ID NO: 11…”).
Kreye also teaches “Anti-spike monoclonal antibody CV07-283 lambda LC, SEQ ID 33” with a 94.8% Query Match to SEQ ID NO: 12 (see Result #12, BKJ13188, us-19-000-508-12.rag, 09/02/2026, in supplemental contents tab).
In view of such teachings or suggestions of Kreye, an antibody comprising VH domain comprising a sequence of at least 90% identity to SEQ ID NO: 136 and VL domain comprising a sequence of at least 90% identity to SEQ ID NO: 33 is considered an obvious embodiment to one of ordinary skill in the art.
Regarding claim 7, Kreye teaches “In some embodiments, the invention relates to a pharmaceutical composition comprising the antibody or fragment thereof of the invention together with a pharmaceutically acceptable carrier”(p. 29) and “When a therapeutically effective amount of the active substance (antibody or antibody fragment) of the invention is administered by intravenous, cutaneous or subcutaneous injection, the active substance may be in the form of a solution, preferably a pyrogen-free, parenterally acceptable aqueous solution”(p. 30).
Regarding claim 8, “The disclosure further relates to corresponding medical uses and therapeutic methods of administering an antibody or antibody fragment of the disclosure in the treatment and/or prevention of a medical condition associated with a SARS Coronavirus”(Abstract).
Regarding claim 9, Kreye teaches “Embodiments of a SARS Coronavirus include, without limitation, any coronavirus that induces a SARS or SARS-similar pathology. Particular embodiments include, without limitation, the SARS Coronavirus (SARS-CoV-1) first discovered in 2003 (as described above), the Middle East respiratory syndrome (MERS-CoV) first discovered in 2012, and the SARS-CoV-2, which causes COVID-19, a disease which brought about the 2019-2020 coronavirus pandemic”(p. 34). Kreye also teaches “Multiple SARS-CoV-2 variants are circulating globally. Additional variants and mutants of SARS-CoV-2 are being discovered regularly. Additional variants comprise, without limitation:…effectively B.1.617.2…is a variant of concern”(p. 35-37). B.1.617.2 is the SARS-CoV-2 Delta variant as evidenced by Mlcochova et al. who states “The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)”(p. 114).
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a base product and process they exemplify. As such, the
claimed product and process recited in claims 1, 6, 7, 8, 9, is within the scope of Kreye’s
invention, and thus Kreye’s invention renders claims 1, 6, 7, 8,and 9 prima facie obvious. The
rationale to support this conclusion of obviousness is that Kreye provides a teaching,
suggestion, and motivation to substitute different variables disclosed within the reference.
Furthermore, there is no evidence on the record that indicates that the claimed product and
process exhibit any unexpected results compared to the prior art.
Conclusion
No claims allowed.
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/C.C./Examiner, Art Unit 1672
/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
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