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
Acknowledgement is hereby made of receipt and entry of the communication filed on June 22, 2026 and Sept. 11, 2024. Claims 1, 2, 4-5, 8-9, 11-12, 14-18, 20-21, 23, 25-26, 30 and 32 are pending. Claims 1, 2, 4-5, 8-9, 11, 15, 18, 23 and 32 are withdrawn. Claims 12, 14, 16-17, 20-21, 25-26, and 30 are currently examined.
Election/Restrictions
Applicant's election without traverse of Group III (claims 12, 14-17, 20-21, 25-26, and 30) in the reply filed on June 22, 2026, is acknowledged.
For species election, based on the species election requirements in the office action filed on 04/22/2026, one type of “antibody or antigen-binding fragment” needs to be elected between claims 14 and 15. Accordingly, the claim 14 is elected for examining in the current office action with option B. Because claim 15 is required both option (a) and (b), therefore, there is no option B can be elected.
Therefore, claims 1, 2, 4-5, 8-9, 11, 18, 23 and 32 are withdrawn as being directed to a non-elected group. Claim 15 is withdrawn as being directed to non-elected species.
Claim Objection
The base claim 12 is objected to because of the following informalities:
The “claim 1” in claim 12 should be removed because the “claim 1” is a withdrawn claim due to the non-elected groups.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 12, 14, 16-17, 20-21, 25-26, and 30 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.
The base claim 12 recites a term “variant” that render the claims indefinite. It is unclear how much difference from the claimed polypeptide can be considered as a “variant”. One of ordinary skill in the art will not know the metes and bounds of the claim.
The base claim 12 and claims 25-26 recite a term “for example” that renders the claims indefinite. It is not clear if this limitation is required or not.
The base claim 12 recites a phrase “the monoclonal antibody or antigen-binding fragment thereof is selected from the group consisting of Fab, Fab', F(ab')2, Fd, Fv, dAb, complementarity determining region fragment, single chain antibody (e.g., scFv), murine antibody, humanized antibody, fully human antibody, chimeric antibody (e.g., human-mouse chimeric antibody), or bispecific or multispecific antibody” that render the claims indefinite because they contain an improper Markush grouping of alternatives.
A Markush-type claim recites alternatives in a format such as “selected from the group consisting of A, B and C.” See Ex parte Markush, 1925 C.D. 126 (Comm’r Pat. 1925).” (MPEP § 803.02).
Also, claim 12 is indefinite because they lack a reference sequence for the cited binding positions “151 to 163 of HRV 2C protein”. One of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention without a reference sequence. Therefore, a sequence of HRV 2C protein referred by SEQ ID NO: should be recited in the claims as a reference for the binding amino acids.
For purposes of compact prosecution and applying prior art, the “151 to 163 of HRV 2C protein” in claim 12 was interpreted herein to encompass amino acid sequences at “YSLPPDPKYFDGY” as disclosed in the instant specification Fig. 1A.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim 14 recited a phrase “a sequence as set of in SEQ ID NO…” that render the claims indefinite. It is not clear if the claimed antibody or antigen-binding fragment “comprise” the SEQ ID NO: sequences or “consist of “the SEQ ID NO: sequences. One of ordinary skill in the art will not know the metes and bounds of the claim.
Claims 14, 16-17 and 21 recite a term “" preferably" that renders the claim indefinite because it is unclear whether the limitations following the phrase are parts of the claimed invention. One of ordinary skill in the art will not know the metes and bounds of the claims.
Claim 14 recites a phrase at “the three CDRs comprised in the VH and/or the three CDRs comprised in the VL are defined by the Kabat, IMGT or Chothia numbering system”, where the ‘defined” renders the claim indefinite because it is not clear what the ‘defined” is represented for. For example, Geneious Biologics (https://help.geneiousbiologics.com/hc/en-us/articles/360044625812-Numbering-Schemes) teaches that the IMGT and Kabat are developed by analyzing alignments of known antibody’s sequences (Kabat) or alignments of the germline genes (IMGT), and Chothia is developed to use structure-based numbering schemes (See page 1). One of ordinary skill in the art will not know the metes and bounds to define a CDR by the claimed numbering system.
Claim 26 recites the term "optionally" that renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h).
The term optionally means "not required or mandatory". For example, a composition comprising A, B, C, and optionally D means that component D can or cannot be present (D is not required to be present). In the rejected claim 26, however, it appears the use of "optionally" is an attempt to define "preferred" embodiments or limitations. Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
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 12, 14, 16-17, 20-21, 25-26, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Elledge et al. (WO 2017 /132550 A1, published on Aug. 03, 2017, hereinafter, “Elledge”) as evidenced by NP_042288 (https://www.ncbi.nlm.nih.gov/protein/NP_042288.1?report=genbank&log$=protalign&blast_rank=2&RID=4ZV9APVA016, Aug. 13, 2018, hereinafter, “NP_042288”) and in view of Cheng et al. (CN105085626A, published on Nov. 25, 2015, hereinafter, “Cheng”) as evidenced by Yin et al. ( Front. Cell. Infect. Microbiol. 14:1347615, 2024), and Taylor et al. (J Mol Recognit. 2000 Mar-Apr;13(2):71-82, hereinafter, “Taylor”).
The base claim 12 is directed to a monoclonal antibody or antigen-binding fragment thereof, wherein the monoclonal antibody is capable of specifically binding to the polypeptide or variant thereof according to claim 1, a recombinant protein or a VLP displaying the polypeptide or variant on its surface, wherein the recombinant protein comprises the polypeptide or variant and a carrier protein, and is not a naturally occurring protein or fragment. For example, the monoclonal antibody is capable of specifically binding to the amino acid residues at positions 151 to 163 of HRV 2C protein.
Elledge teaches detecting an antibody directed against a pathogen that infect human including the Rhinovirus (See Abstract and [0005]). The method for detecting an antibody against a Rhinovirus comprises (a) contacting a reaction sample comprising a display library with a biological sample comprising antibodies, wherein the display library comprises a plurality of peptides derived from a plurality of pathogens, and (b) detecting a peptide bound to at least one antibody, thereby detecting an antibody capable of binding the peptide (See [0006]), where the display library can be a phage display library ([0008). Here Elledge discloses a peptide sequence library generation through the T7-Select 10-3b system that produces peptides encoded by DNA as fusions to the exterior coat proteins of T7 bacteriophage particles. Each bacteriophage particle contains DNA encoding a peptide fused to the C-terminus of the T7 gene 10 protein (See [000163]), which teaches that a recombinant protein contains a peptide epitope and a carrier protein, T7 gene 10 protein, on its surface. Because the T7 gene 10 protein is inserted by the pathogen peptide, so it is not a naturally occurring protein as claimed.
At the same time, Elledge teaches peptides that contain an identical sequence of the 151 to 163 of HRV 2C protein with the sequence “YSLPPDPKYFDGY” (See 112b rejection above; Elledge’s Table 4). Elledge teaches that “Table 4 are exemplary peptides from a plurality of viruses and viral families that can bind antibodies generated by a subject in response to the virus. That is, the peptides described in Table 4 act as epitopes for antibodies present in a biological sample, permitting the detection and/or identification of antibodies generated against a particular virus or plurality of viruses (See [000211]). Among the peptide epitopes in Table 4, peptide 93579 (IYSLPPDPKYFDGYDQQSVVIMDDIMQNPTGDDMTLFCQMVSSVTFIPPMADLPDK ) and 25072 (KSLATSVLARMLTVETDIYSLPPDPKYFDGYDQQSVVIMDDIMQNPSGEDMTLFC) contains the identical epitope sequence of “YSLPPDPKYFDGY”. Although Elledge does not explicitly point out that the peptides 93579 and 25072 is part of the HRV 2C protein, BLAST results can be evidence that these two epitopes are part of the HRV 2C protein. For example, Table A below shows peptide 93579 is part of the HRV P2-C/2C protein (See Accession # NP_042288.1). NP_042288.1 discloses the genome polyprotein [Rhinovirus A] and teaches that amino 1104…1424 is P2-C polypeptide/protein 2C.
Accordingly, Elledge teaches the claimed amino acid residues at positions 151 to 163 of HRV 2C protein.
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As for the monoclonal antibody, although Elledge does not explicitly use the term “monoclonal antibody”, Elledge teaches CDR and V(D)J and states that it is possible that, rather than being an exception for dengue specific antibodies, this represents a general phenomenon: inherent biases in V(D)J recombination generate the same or similar antibodies in multiple individuals that recognize highly similar epitopes (See [000195]). Here the description indicates that a monoclonal antibody with specified CDRs has been identified to be capable of specifically binding to a specific epitope, wherein it is obvious include the epitopes in the HRV 2C protein.
Nevertheless, Cheng describes a broad-spectrum affinity epitope polypeptide and antibody for human enteroviruses and teaches that the inventors prepared monoclonal antibodies, identified and obtained a hybridoma cell line, which can produce a specific reaction with the epitope polypeptide of the present invention of monoclonal antibodies (See page 3, paragraph 3). Cheng also teaches that the isolated epitope polypeptide can be the enterovirus nonstructural protein 2C from one of SEQ ID NO: 1 and 22-85 (See page 1, claim 1), where the SEQ ID NO: 77 contains an identical sequence with the epitope of “YSLPPDPKYFDGY” (See Table B below). It is noted that Cheng’s invention is focused on human enterovirus and not the human Rhinovirus. However, both rhinovirus and enterovirus belong to the Picornaviridae family, and 2C proteins are highly conserved among them. This can be evidenced by Yin’s study. Yin teaches that among the nonstructural proteins in picornaviruses of enterovirus 71 (EVA71), poliovirus (PV), coxsackievirus (CV), rhinovirus (RV), and hepatitis A virus (HAV), 2C proteins are highly conserved and exhibit multiple structural domains, including amphipathic a-helices, an ATPase structural domain, and a zinc finger structural domain (See Abstract and page 2, left column).
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Therefore, Cheng teaches a human monoclonal antibody to bind the 2C protein in Picornaviridae family including enterovirus and rhinovirus and can be used as for treating and/or preventing and/or diagnosing human enterovirus and/or identifying human enterovirus titer and/or identifying the drug or method of human enterovirus neutralizing antibody titer middle (See Abstract).
As for the alternative limitation of the VLP displaying the polypeptide or variant on its surface, Elledge is silent on the VLP.
However, Taylor teaches constructing a series of cowpea mosaic virus (CPMV) chimaeras expressing the 14 amino acid NIm-1A epitope from human rhinovirus 14 (HRV-14) at different positions on the capsid surface. Biochemical and crystallographic analysis of a CPMV/HRV chimaera expressing the NIm-1A epitope inserted into the βC'–βC” loop of the S protein. Polyclonal antisera raised against the CPMV/HRV chimaera presenting the NIm-1A epitope as a closed loop had a significantly enhanced ability to bind to intact HRV-14 particles. These results demonstrate that the mode of presentation of an epitope on a heterologous carrier can dramatically affect its immunological properties (See Abstract). Accordingly, Taylor teaches an antibody (polyclonal serum) specifically bind to a polypeptide (14 amino acid NIm-1A epitope) of HRV and the polypeptide is displayed on the surface of a plant virus (CPMV) through a VLP system, where the carrier protein is the CPMV S protein (See page 72, right column, paragraph 3).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings from Elledge, Cheng and Taylor to arrive at an invention as claimed. One of skill in the art would have been motivated to do so to introduce the VLP system of Taylor and the monoclonal antibody of Cheng into Elledge’s invention to generate the monoclonal antibody by hybridoma cells of Cheng to specifically bind to the peptide presented on the surface of a carrier through VLP. Cloning is a routine technique in the art. One of skilled in the art can replace the NIm-1A epitope by the claimed peptide epitope of “YSLPPDPKYFDGY” in Taylor’s VLP system. There would be a reasonable expectation of success to develop such a monoclonal antibody or antigen-binding fragment as claimed.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 16, Although Elledge is silent on a humanized antibody, Cheng teaches that in certain embodiments, the antibody is selected from monoclonal antibodies, polyclonal antibodies, chimeric antibodies, humanized antibodies (See e.g., page 6, paragraph 2). It would be obvious for one of ordinary skill in the art to introduce the humanized antibody of Cheng’ into Elledge’s invention to arrive at an invention as claimed, and the result for generating a humanized antibody would be predictable based on Cheng’s teaching.
Regarding claim 17, It is a common knowledge that a natural and full-sized antibody requires both variable region and constant region. Elledge teaches detecting an antibody directed against a pathogen (See Abstract), where the antibody can be the full-size antibody with constant region. Nevertheless, Cheng teaches a constant region by stating that the terms "heavy chain", "light chain", "variable region", "framework region", "constant region" etc. have their ordinary meaning in the field of immunology and refer to naturally occurring immune Domains in globulins and corresponding domains of synthetic (eg, recombinant) binding proteins (eg, humanized antibodies, single chain antibodies, chimeric antibodies, etc.). The carboxy-terminal ("c") portion of each chain defines a constant region, with light chains having a single constant domain and heavy chains typically having three constant domains and a hinge region (See page 8, paragraph 6). It would be obvious for one of ordinary skill in the art to introduce the constant region of Cheng into Elledge’s study to arrive at an invention as claimed, and the result would be predictable based on Cheng’s teaching.
Regarding claims 20-21, Elledge does not explicitly point out using an expression vector containing the isolated nucleic acid molecule encoding the antibody, but Cheng teaches that their claim 15 is for an isolated nucleic acid molecule comprising a nucleic acid sequence encoding the antibody or antibody fragment, and claim 16 is for a vector comprising the isolated nucleic acid molecule of claim 15 (See page 2, paragraph 1). It would be obvious for one of ordinary skill in the art to introduce the vector with the isolated nucleic acid of Cheng into Elledge’s study to express the antibody as claimed, and the result would be predictable based on Cheng’s teaching.
Regarding claim 25, Elledge teaches that the label can be "direct", e.g., a dye, or "indirect", e.g., biotin, digoxin, alkaline phosphatase (AP), horse radish peroxidase (HRP). For detection of "indirect labels" it is necessary to add additional components such as labeled antibodies, or enzyme substrates to visualize the captured, released, labeled polynucleotide fragment (See page 27, paragraph 1). It is obvious that an antibody conjugated with AP or HRP is a conjugate.
Regarding claims 26 and 30, Elledge does not explicitly point out a kit and a pharmaceutical composition, however, Cheng teaches that a kit comprises the antibody or antibody fragment or the antibody conjugate, and a composition comprising the antibody or fragment thereof or the antibody conjugate. Preferably, the composition comprises a pharmaceutically acceptable carrier or excipient; Preferably, the composition is a pharmaceutical composition or a diagnostic composition (See page 2, paragraph 1). It would be obvious for one of ordinary skill in the art to introduce the kit and the pharmaceutical composition of Cheng into Elledge’s study to arrive at an invention as claimed.
Allowable Subject Matter
The SEQ ID NOs: 19, 23-29 in claim 14 are free of prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am to 4:30 pm, EST.
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/RUIXUE WANG/ Examiner, Art Unit 1672
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