DETAILED ACTION
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 .
Claim Status
Claims 1-15 are under examination (7/28/2022). Claims 16-46 are cancelled (7/28/2022).
Priority
Claims 1-15 receive a priority date of 12/3/2019, the effective filing date of Korean Provisional Patent KR10-2019-0158887.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure
statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information
submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be
incorporated into the specification but must be submitted in a separate paper." Therefore, unless
the references have been cited by the examiner on form PTO-892, they have not been
considered.
Information disclosure statement (IDS) was submitted on 6/3/2022, and is being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities (see MPEP § 608.01):
The use of the terms “Tween 20” (p. 7, 25-26, 35), “Tween 30” (p. 7), “Tween 40” (p. 7), “Tween 60” (p. 7), “Tween 80” (p. 7), “Triton X-“ (p. 7), “Polyoxyethylene Ether W-1” (p. 7), “Span-“ (p. 7), “Dynabeads” (p. 14), “Pierce” (p. 14), “Thermo Scientific Inc” (p. 14, 26, 30, 36, 38), “GE Healthcare” (p. 14), “Biomag” (p. 14), “ProMag” (p. 14), “Microspheres-Nanospheres” (p. 14), “Spherotech” (p. 14), “Illumina” (p. 15), “Life Technology” (p. 15, 25), “Pacific Biosciences” (p. 15), “PacBio” (p. 15), “Alexa Fluor” (p. 16), “TaqMAN” (p. 17), “Fisher Scientific” (p. 25), “American International Chemical” (p. 25), “Sigma-Aldrich” (p. 25), “Gold Technology” (p. 25), “Moss, Inc.” (p. 25), “Avantor” (p. 25), “Baonia” (p. 26), “Bioneer” (p. 26), “Perkin-Elmer” (p. 28), “Qiagen” (p. 28), “Dynabeads” (p. 30), and “Ion Torrent” (p. 38), which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Claim Objections
Claim 3 is objected to because of the following informality:
Claim 3 at lines 4-5; “in vitro” should be italicized.
Claim 14 is objected to because of the following informality:
Claim 14 at line 3; “step (f) in a form” should be replaced with “step (f) is in a form.”
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 1-15 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 recites the limitation "the first solid support" in line 7. There is insufficient antecedent basis for this limitation in the claim.
Claims 2-15 are included in this rejection due to their dependency on claim 1.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-15 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Kochetkova et al. (WO 2011/123903 A1; published 10/13/2011).
Regarding claims 1-2, Kochetkova teaches a method that includes producing an aptamer library, for example, by cloning random oligonucleotides into a vector (or an expression vector in the case of an RNA aptamer), wherein the random sequence is flanked by known sequences that provide the site of binding for PCR primers (p. 55, lines 1-5). Further, Kochetkova teaches that a nucleic acid aptamer is a nucleic acid that is capable of forming a secondary and/or tertiary structure that provides the ability to bind to a molecular target, e.g., a heteromultimer (p. 54, lines 35-36). Kochetkova further teaches the application of chemotaxis assays which monitor the directional movement or migration of a suitable cell into or through a barrier (e.g., endothelium, a filter), toward increased levels of a compound, from a first surface of the barrier toward an opposite second surface (p. 59, lines 5-10). Specifically, Kochetkova teaches that in one example, the cells are labeled with a detectable tag (e.g., radioisotope, fluorescent label, antigen or epitope label), and migration can be assessed in the presence and absence of the binding
molecule by determining the presence of the label adherent to the membrane and/or present in the second chamber using an appropriate method (e.g., by detecting radioactivity, fluorescence, immunoassay) (p. 59, lines 25-30).
Kochetkova also teaches that the previously described method can be applied to specified proteins, creating complex populations such as "CXCR4-CCR7 heteromultimer", which is intended to mean a protein complex comprising at least one CXCR4 monomer in contact with at least one CCR7 monomer (p. 24, lines 20-25). Specifically, Kochetkova teaches that a heteromultimer in which one or both of CXCR4 and CCR7 is a fusion protein where, the protein is fused to a tag or label and in some examples, a tag or label facilitates purification or isolation or detection of the protein where suitable tags will be apparent to the skilled artisan and
include, for example, influenza virus hemagglutinin (HA), Simian Virus 5 (V5),
polyhistidine (e.g., hexa-HIS), c-myc or FLAG (p. 35, lines 20-30). Further, Kochetkova teaches that in some examples, the CXCR4-CCR7 heteromultimer binding molecules may specifically bind to an epitope of the CXCR4-CCR7 heteromultimer (p. 37, lines 25-35). Kochetkova later teaches that the bound protein is then detected using a second labeled compound that binds to a different protein or a different site in the same protein and alternatively, a third labeled antibody can be used that binds the second (detecting) antibody (p. 84, lines 15-20).
Also, Kochetkova teaches that in one example, the assay used to determine the amount or level of a heteromultimer is a semi-quantitative method and in another embodiment the assay used to determine the amount or level of a heteromultimer is a quantitative method (p. 83, lines 15-20).
Regarding claim 3, Kochetkova teaches that the previously described aptamer profile method includes methods for identifying agents that block association between CXCR4 and
CCR7 may include rational drug or protein design, screening methods and/or raising
antibodies against CXCR4 and/or CCR7 epitopes (p. 100, lines 15-20).
Regarding claim 4, Kochetkova teaches that the previously described aptamer profile method includes a binding molecule (e.g., an antibody) that is brought into direct contact with the immobilized biological sample, and forms a direct bond with any of its target protein present in said sample (p. 83, lines 30-35).
Regarding claim 5, Kochetkova teaches that the previously described aptamer profile method includes "antigen binding fragment" which shall be taken to mean any fragment of an antibody that retains at least one variable or unknown targeted region of an antibody and the ability to bind to the target protein or heteromultimer preferably specifically or selectively (p. 26, lines 5-10).
Regarding claim 6, Kochetkova teaches that the previously described aptamer profile method includes a collection of DNA molecules that can then be used to create "synthetic libraries" of antibodies or fragments thereof, e.g., Fv, disulphide-linked Fv, single-chain Fv (scFv), Fab fragments, or Fab' fragments which may be used as sources of proteins that bind
specifically, to an antigen (p. 40, lines 25-35). Kochetkova further teaches that for example, a diabody is a protein comprising two associated polypeptide chains, each polypeptide chain comprising the structure VL-X-VH or VH-X-VL, wherein VL is an antibody light chain variable region, V H is an antibody heavy chain variable region, X is a linker comprising insufficient residues to permit the VH and VL in a single polypeptide chain to associate (or form an Fv) or is absent, and wherein the VH of one polypeptide chain binds to a VL of the other polypeptide chain to form an antigen binding site, i.e., to form a Fv molecule capable of specifically binding to one or more antigens and the VL and VH can be the same in each polypeptide chain or the VL
and V H can be different in each polypeptide chain so as to form a bispecific diabody
(i.e., comprising two Fvs having different specificity) (p. 46, lines 15-25). Specifically, Kochetkova teaches a method for amplifying (e.g., by PCR), cloning, and expressing antibody variable region genes via starting with these genes he was able to create libraries of functional antibody fragments (p. 40, lines 30-35).
Regarding claim 7, Kochetkova teaches that the previously described aptamer profile method includes in another example a binding molecule is contacted to an immobilized CXCR4-
CCR7 heteromultimer or a membrane comprising same or a cell expressing same where following washing to remove any unbound or non-specifically bound molecules,
binding molecules capable of binding to the heteromultimer are selected and/or
identified and optionally, the molecule is labeled (e.g., with a detectable tag, such as a
fluorescent label) to facilitate detection (p. 56, lines 15-20). Further, Kochetkova teaches that the identified/isolated binding molecules are then contacted with immobilized CXCR4 or CCR7 monomer or homomultimer or membrane comprising same or cell expressing same. Binding molecules that do not bind are then identified/isolated (p. 56, lines 20-35). Specifically, Kochetkova teaches that cells are washed and cultured in the presence or absence of a binding molecule and/or a ligand that activates the heteromultimer in inositol free medium (p. 58, lines 1-10).
Regarding claims 8-9, Kochetkova teaches that the previously described aptamer profile method includes an agent that may comprise an isolated protein, a small molecule, a DNA sequence, an RNA sequence, an aptamer, an antibody, a ligand, a fusion protein, siRNA, an antisense molecule, microRNA, shRNA, etc. (p. 65, lines 1-5). Further, Kochetkova teaches that for example, targeted profiles may include "epitopes", which include chemically active surface groupings of molecules such as sugar side chains, phosphoryl side chains, or sulfonyl side chains, and, in certain embodiments, may have specific three-dimensional structural characteristics, and/or specific charge characteristics (p. 28, lines 5-15).
Regarding claim 10, Kochetkova teaches that the previously described aptamer profile method includes that in one form such an assay involves immobilizing a biological sample onto a
solid matrix, such as, for example a polystyrene or polycarbonate microwell or dipstick,
a membrane, or a glass support (e.g. a glass slide) (p. 83, lines 25-35).
Regarding claim 11, Kochetkova teaches that in one example, the cells are labeled with a detectable tag (e.g., radioisotope, fluorescent label, antigen or epitope label), and migration can be assessed in the presence and absence of the binding molecule by determining the presence of the label adherent to the membrane and/or present in the second chamber using an appropriate method (e.g., by detecting radioactivity, fluorescence, immunoassay) (p. 59, lines 25-30).
Kochetkova further teaches that the previously described aptamer profile method includes an antigen that is preferably bound to another molecule to allow for ease of purification, such as, for example, a molecule selected from the group consisting of protein G, Sepharose, agarose, biotin, glutathione Stransferase (GST), and FLAG epitope (p. 42, lines 5-15).
Regarding claim 12, Kochetkova teaches that the previously described aptamer profile method includes that in one form such an assay involves immobilizing a biological sample onto a
solid matrix, such as, for example a polystyrene or polycarbonate microwell or dipstick,
a membrane, or a glass support (e.g. a glass slide) (p. 83, lines 25-35). Kochetkova alternatively, or in addition, teaches that the binding molecule is labeled with, for example, a magnetic or paramagnetic compound, such as, iron, steel, nickel, cobalt, rare earth materials, neodymium-iron-boron, ferrous-chromium-cobalt, nickel-ferrous, cobalt platinum, or strontium ferrite (p. 63, lines 20-25).
Regarding claims 13-14, Kochetkova teaches that the previously described aptamer profile’s solid support method includes CXCR4-CCR7 heteromultimers which comprise one or more CXCR4-CCR7 binding interfaces and accordingly, in some embodiments, the agent may inhibit the formation of a CXCR4-CCR7 heteromultimer by interfering with a binding interface and for example, an agent which is capable of binding to a portion of a CXCR4-CCR7 binding interface may be used to competitively inhibit the formation of the heteromultimer or to disrupt a CXCR4-CCR7 heteromultimer or the agent comprises a region of CCR7 that interacts with
CXCR4 (p. 67-68, lines 30-40). Further, Kochetkova teaches that in another example a binding molecule is contacted to an immobilized CXCR4-CCR7 heteromultimer or a membrane comprising same or a cell expressing same where following washing to remove any unbound or non-specifically bound molecules, binding molecules capable of binding to the heteromultimer are selected and/or identified and optionally, the molecule is labeled (e.g., with a detectable tag, such as a fluorescent label) to facilitate detection where the identified/isolated binding molecules are then contacted with immobilized CXCR4 or CCR7 monomer or homomultimer or
membrane comprising same or cell expressing same and binding molecules that do not
bind is then identified/isolated (p. 56, lines 15-25). Also, Kochetkova teaches that specified compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, for example, sodium acetate, sodium chloride, potassium chloride,
calcium chloride, sodium lactate and the like (p. 70, lines 1-5).
Regarding claim 15, Kochetkova teaches that the previously described aptamer profile method can be applied to high throughput formats, such as, for example, automation of screening processes or a microarray format (p. 84, lines 25-35).
Kochetkova teaches each and every limitation of claims 1-15 and therefore Kochetkova anticipates claims 1-15.
Conclusions
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ROSE LAFAVE whose telephone number is (703)756-4747. The examiner can normally be reached Compressed Bi-Week: M-F 7:30-4:30.
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/ELIZABETH ROSE LAFAVE/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684