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
Pursuant to a preliminary amendment filed March 30, 2026 claims 1-28 are currently pending in the instant application.
Response to Election/Restriction
Applicant's election of Group I, claims 1-8, 12 and 13, directed to a method for purifying a target molecule; and Applicant’s election of Species with traverse as follows:
Species (A): further comprising panning the phage library against at least one antigen to generate a library of phage clones (claim 4);
Species (B): the quantity of polynucleotides comprising a single-chain variable fragment in the form of gapped, double-stranded vectors wherein the gap exposes the scFv as a single-stranded segment (scFv) (claim 45); and
Species (C)-(E): are directed to non-elected Groups, in the reply filed March 30, 2026 is acknowledged.
Response to Traversals:
The traversal of is on the grounds that: (a) all of the method claims (Groups I-V) recite or depend on methods requiring diversifying with AID and further diversifying with Pol h (Applicant Remarks, pg. 10 through pg. 11, second full paragraph); and (b) regarding Species (B), the quantity of polynucleotides (claim 10 or 11) does not conflict with or preclude what form the gene of the polynucleotide has (claim 12) or the vector (claim 13); the gene and vector and its form can co-exist (Applicant Remarks, pg. 12, last partial paragraph; and pg. 13, first partial paragraph).
Regarding (a), the Examiner notes that claims 1, 9, 14, 16 and 18 are independent claims, such that they cannot “depend” from another independent claim. Moreover, an independent claim should not refer back to another independent claim because an independent claim is a stand-alone claim that contains all the limitations necessary to define an invention. Thus, as indicated in the Office Action mailed January 30, 2026, Groups I-V do not share the same or corresponding special technical feature including ‘diversifying with AID and further diversifying with Pol h’ as suggested by Applicant. Thus, Groups I-V lack unity of invention, such that the restriction is proper.
Regarding (b), Applicant has amended claim 12 to depend from claim 7, and has amended claim 13 to depend from claim 12, such that claims 12 and 13 no longer depend from instant claim 9. Thus, the argument with respect to claims 12 and 13 is moot.
Claims 9, 10 and 14-28 ae withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 2, 3, 6 and 8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on March 30, 2026.
The restriction requirement is still deemed proper and is therefore made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 4, 5, 7, 12 and 13 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed November 30, 2022 is a 35 U.S.C. 371 national stage filing of International Application PCT/US2021/035528, filed June 2, 2021, which claims the benefit US Provisional Patent Application 63033429, filed June 2, 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on November 30, 2022 and March 30, 2026 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Claim Objections
Claims 1, 4, 5, 7, 12 and 13 are objected to because of the following informalities: a clean copy of the claims is respectfully requested because Applicant has made a multitude of changes to the claims resulting in significant portions of the recitation being lined-through, such that the claims are visually challenging to the Examiner, and it is difficult for the Examiner to correctly decipher the claimed invention.
Claim Rejections - 35 USC § 112(b)
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, 4, 5, 7, 12 and 13 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “the further diversified library” such as recited in claim 1, line 7. There is insufficient antecedent basis for the term “the further diversified library” in the claim because claim 1, line 2 recites the term “a library of phage or phagemid clones.”
Claim 4 is indefinite for the recitation of the term “a library of phage vectors or phagemid vectors inserted with a native IgV gene or a gene encoding a VH and/or a VL of the native IgV gene” and/or “native IgV genes”, such as recited in claim 4, lines 2-3 because the as-filed Specification and original claims do not teach or recite native IgV genes and/or a library of phage vectors or phagemid vectors inserted with a native IgV gene or gene encoding a VH and/or VL of the native IgV gene and, thus, the metes and bounds of the claims cannot be determined.
Claim 4 is indefinite for the recitation of the terms “the naïve IgV gene or the gene encoding the VH and/or VL” such as recited in claim 4, line 4. There is insufficient antecedent basis for the term “the naïve IgV gene or the gene encoding the VH and/or VL” in the claims because claim 4, line 3 recites the term “a native IgV gene or gene encoding a VH and/or VL of the native IgV gene”. Moreover, it is unclear whether the term “native” and “naïve” are intended to be used interchangeably and/or whether the terms refer to different genes and, thus, the metes and bounds of the claims cannot be determined.
Claims 5 and 12 are indefinite for the recitation of the terms “the naïve IgV gene or the genes” such as recited in claim 5, lines 4-5. There is insufficient antecedent basis for the term “the naïve IgV gene or the genes” in the claim because claim 5, line 3 recites the term “a library of naïve IgV genes or genes comprising a polynucleotide encoding a VH and/or a VL of the naïve IgV genes”.
Claim 5 is indefinite for the recitation of the terms “the IgV genes or the genes encoding the VH and/or VL of the IgV genes” such as recited in claim 5, lines 8-10. There is insufficient antecedent basis for the term “the IgV genes or the genes encoding the VH and/or VL of the IgV genes” in the claim because claim 5, line 3 recites the term “a library of naïve IgV genes or genes comprising a polynucleotide encoding a VH and/or a VL of the naïve IgV genes”.
Claim 5 is indefinite for the recitation of the terms “diversifying a library of naïve IgV gene or genes comprising a polynucleotide encoding a VH and/or a VL of the naïve IgV gene”; “the IgV genes or the genes encoding VH and/or VL of the IgV genes”; a “deaminated library”; “cloning”; “panning”; “at least one antigen”; and a “further diversified library” such as recited in claim 5, lines 2-18 because claim 5 depends from instant claim 1, wherein claim 1 does not recite the presence of a library of naïve IgV gene or genes comprising a polynucleotide encoding a VH and/or a VL of the naïve IgV gene; the IgV genes or the genes encoding VH and/or VL of the IgV genes; a deaminated library; cloning; panning; at least one antigen; and a further diversified library. Moreover, the as-filed Specification and original claims do not teach or recite diversifying a library of naïve IgV gene or genes comprising a polynucleotide encoding a VH and/or a VL of the naïve IgV gene and, thus, the metes and bounds of the claims cannot be determined.
Claim 5 is indefinite for the recitation of the terms “diversifying”; “further diversifying”; “generating a further diversified library”; “contacting…with AID”; and “cloning the further diversified library”; and “generating a library of phage or phagemid vectors containing diversified IgV genes or diversified genes encoding the VH and/or VL” in claim 5, lines 4-19 because the different steps appear to encompass the entire process recited in instant claim 1, such that it encompasses more than the step of “providing” as recited in claim 1, line 2 (and claim 5, lines 1-2). Moreover, the steps as recited in claim 1 result in generating phage particles or phagemid particles and not, as recited here, phage or phagemid clones and, thus, the metes and bounds of the claims cannot be determined.
Claim 7 is indefinite for the recitation of the terms “the library of phage vectors or phagemid vectors inserted with the naïve IgV genes encoding the VH and/or VL of the IgV genes” such as recited in claim 7, lines 1-2. There is insufficient antecedent basis for the term “the library of phage vectors of phagemid vectors inserted with the naïve IgV genes” in the claim because claim 4, lines 2-3 recites the term “a library of native IgV genes”.
Claims 7 and 12 are indefinite for the recitation of the term “native IgV gene” such as recited in claim 7, line 3 because the as-filed Specification and original claims do not teach or recite a “native IgV gene” and, thus, the metes and bounds of the claim cannot be determined.
Claim 7 is indefinite for the recitation of the term “the library of phage vectors or phagemid vectors inserted with the naïve IgV gene or the gene encoding the VH and/or the VL of the native IgV gene”; “quantity of gapped, double stranded DNA vectors”; and “a segment which exposes the naïve IgV gene…in a single-stranded form” such as recited in claim 7, lines 1-6 because claim 7 depends from instant claims 1 and 4, where claims 1 and 4 do not recite a library of phage vectors or phagemid vectors inserted with the naïve IgV gene or the gene encoding the VH and/or the VL of the native IgV gene; gapped, double stranded DNA vectors; and/or a segment which exposes the naïve IgV gene…in a single-stranded form and, thus, the metes and bounds of the claims cannot be determined.
Claim 7 is indefinite for the recitation of the term “a segment which exposes the naïve IgV gene…in a single-stranded form” such as recited in claim 7, lines 4-6 because it is completely unclear how (or what is meant by) a segment of a double-stranded DNA vector exposes the naïve IgV gene (or the gene encoding the VH and/or VL of the native IgV gene) in a single-stranded form and, thus, the metes and bounds of the claims cannot be determined.
Claim 7 is indefinite for the recitation of the term “the other strand” such as recited in claim 7, line 6. There is insufficient antecedent basis for the term “the other strand” in the claim.
Claim 12 is indefinite for the recitation of the term “the providing of the library of the phage vectors or phagemid vectors inserted with the native IgV gene or the gene encoding the VH and/or the VL of the native IgV gene” such as recited in claim 12, lines 2-4 because claim 12 depends from claims 1, 4 and 7, wherein claim 7, lines 1-3 already recites that the phage or phagemid vectors inserted with the naïve IgV gene is provided in a quantity of gapped, double stranded DNA vectors. Moreover, claim 4 recites vectors inserted with a native IgV gene; while claim 7 recites vectors inserted with the naive IgV gene, such that the claim is confusing and unclear. Thus, the steps as recited provide the incorrect phage and/or phagemid vectors and, thus, the metes and bounds of the claims cannot be determined.
Claim 13 is indefinite insofar as it ultimately depends from instant claim 1.
Claim Rejections - 35 USC § 112(d)
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.
Claims 5, 7 and 12 are rejected under 35 U.S.C. 112(d) 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.
Claim 5 recites (in part): “wherein the providing of the library of phage or phagemid clones comprises: diversifying a library of naïve IgV genes or genes comprising a polynucleotide encoding a VH and/or VL of the naïve IgV genes…against at least one antigen to produce the library of phage or phagemid clones” in lines 1-19 because claim 5 depends from instant claim 1, wherein claim 1 does not recite the presence of a library of naïve IgV gene or genes comprising a polynucleotide encoding a VH and/or a VL of the naïve IgV gene; the IgV genes or the genes encoding VH and/or VL of the IgV genes; a deaminated library; cloning; panning; at least one antigen; and a further diversified library. Thus, claim 5 is an improper dependent claims for failing to further limit the subject matter of the claim upon which they depend, or for failing to include all the limitations of the claim upon which they depends.
Claim 7 recites (in part): “wherein the library of phage vectors or phagemid vectors inserted with the naïve IgV genes…resulting in a gap in the other strand of each double stranded DNA vector” in lines 1-7 because claim 7 depends from instant claims 1 and 4, where claims 1 and 4 do not recite a library of phage vectors or phagemid vectors inserted with the naïve IgV gene or the gene encoding the VH and/or the VL of the native IgV gene; gapped, double stranded DNA vectors; and/or a segment which exposes the naïve IgV gene…in a single-stranded form. Thus, claim 7 is an improper dependent claims for failing to further limit the subject matter of the claim upon which they depend, or for failing to include all the limitations of the claim upon which they depends.
Claim 12 recites (in part): “wherein the providing of the library of the phage vectors or phagemid vectors inserted with the native IgV gene…as a single-stranded segment in the at least one of the re-annealed vectors” in lines 1-14 because claim 12 depends from claims 1, 4 and 7, wherein claim 7 already recites that the vectors are provided in a quantity of gapped, double stranded DNA vectors. Moreover, claim 7 recites “the library of phage vectors or phagemid vectors inserted with the naive IgV gene or the gene encoding the VH and/or the VL of the native IgV gene is provided”. Thus, claim 12 is an improper dependent claims for failing to further limit the subject matter of the claim upon which they depend, or for failing to include all the limitations of the claim upon which they depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1, 4, 5, 7, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Tveita et al. (hereinafter “Tveita”) (US Patent No. 11186641, published November 30, 2021; effective filing date September 21, 2017) in view of Liu et. al. (hereinafter “Liu ‘496”) (US Patent No. 11542496, issued January 3, 2023); and further in view of Kramer (Nucleic Acids Research, 1984, 12(24), 9441-9456).
Regarding claims 1 (in part), Tveita teaches that the immunoglobulin single variable domain is a nanobody (col 2, lines 46-47). Tveita teaches screening for nanobodies, as a non-limiting example, specifically binding to a TAM targeting protein can, for example, be performed by screening a set, collection or library of cells that express heavy chain antibodies on their surface (e.g., B-cells obtained from a suitably immunized Camelid), or bacteriophages that display a fusion of genIII and nanobody at their surface, by screening of a (naive or immune) library of VHH sequences or nanobody sequences, or by screening of a (naive or immune) library of nucleic acid sequences that encode VHH sequences or nanobody sequences, which can all be performed in a manner known per se, and which method can optionally further comprise one or more other suitable steps, such as, for example, and without limitation, a step of affinity maturation, a step of expressing the desired amino acid sequence, a step of screening for binding and/or for activity against the desired antigen (in this case, the TAM targeting protein), a step of determining the desired amino acid sequence or nucleotide sequence, a step of introducing one or more humanizing substitutions, a step of formatting in a suitable multivalent and/or multi-specific format, a step of screening for the desired biological and/or physiological properties (i.e., using a suitable assay known in the art), and/or any combination of one or more of such steps, in any suitable order (interpreted as providing a library of phage or phagemid clones; and a naïve IgV gene or a gene encoding the VH and/or VL, claims 1, 4, 5, 7 and 12) (col 18, lines 13-37). Tveita teaches the use of the fusion proteins described herein to generate a cancer specific immune response in a subject, wherein the cancer is, for example, lung cancer, breast cancer, pancreatic cancer, prostate cancer, melanoma or multiple myeloma (col 4, lines 35-39). Tveita teaches that the V-gene library cloned from the immunization-derived antibody repertoire can be expressed by a population of display packages, preferably derived from filamentous phage, to form an antibody display library (interpreted as a library of phage or phagemid clones; and providing the library, claims 1, 5 and 12) (col 25, lines 46-49). Tveita teaches that once displayed on the surface of a display package (e.g., filamentous phage), the antibody library is screened with the target antigen, or peptide fragment thereof, to identify and isolate packages that express an antibody having specificity for the target antigen; and the nucleic acid encoding the selected antibody can be recovered from the display package (e.g., from the phage genome) and subcloned into other expression vectors by standard recombinant DNA techniques (interpreted as contacting the library of phage of phagemid clones; and inserting vectors with a gene encoding a VH and/or VL of the naïve IgV gene, claims 1 and 4) (col 26, lines 21-28). Tveita teaches that a variegated peptide library is expressed by a population of display packages to form a peptide display library, such that the display package comprises a system that allows the sampling of very large variegated peptide display libraries, rapid sorting after each affinity separation round, and easy isolation of the peptide encoding gene from purified display packages, wherein peptide display libraries can be in, e.g., prokaryotic organisms and viruses, which can be amplified quickly, are relatively easy to manipulate, and which allows the creation of large number of clones, wherein display packages include, for example, vegetative bacterial cells, bacterial spores, and most preferably, bacterial viruses (especially DNA viruses) (interpreted as a library of phage or phagemid clones; and transfecting a library into microbes, claim 1) (col 26, lines 48-60). Tveita teaches that in order to produce viral particles containing a membrane associated protein that will permit entry of the virus into a cell, the packaging cell line containing the retroviral sequences is transfected with sequences encoding a membrane-associated protein (e.g., the G protein of vesicular stomatitis virus [VSV]), wherein the transfected packaging cell will then produce viral particles that contain the membrane-associated protein expressed by the transfected packaging cell line (interpreted as transfecting into microbes; and obtaining a library of phage particles, claim 1) (col 37, lines 8-16).
Regarding claims 4, 5, 7 (in part) and 12 (in part), Tveita teaches that the nanobodies of the invention can be obtained: (1) by isolating the VHH domain of a naturally occurring heavy chain antibody; (2) by expression of a nucleotide sequence encoding a naturally occurring VHH domain; (3) by "humanization" of a naturally occurring VHH domain or by expression of a nucleic acid encoding a such humanized VHH domain; (4) by "camelization" of a naturally occurring VH domain from any animal species, and in particular from a mammalian species, such as from a human being, or by expression of a nucleic acid encoding such a camelized VH domain; (5) by "camelization" of a "domain antibody" or "Dab" as described in the art, or by expression of a nucleic acid encoding such a camelized VH domain; (6) by using synthetic or semi-synthetic techniques for preparing proteins, polypeptides or other amino acid sequences known per se; (7) by preparing a nucleic acid encoding a nanobody using techniques for nucleic acid synthesis known per se, followed by expression of the nucleic acid thus obtained; and/or (8) by any combination of one or more of the foregoing (interpreted as providing a library of phage or phagemid clones as recited in claims 4, 5 and 12) (col 17, lines 4-23). Tveita teaches that naturally occurring VHH domains against MMR can be obtained from naive libraries of Camelid VHH sequences, for example, by screening such a library using MMR or at least one part, fragment, antigenic determinant or epitope thereof using one or more screening techniques known per se (interpreted as providing the library of phage clones; and a phage vector inserted with a naïve gene, claims 4 and 5) (col 17, lines 36-41). Tveita teaches that the peptides, polypeptides, and proteins of the present invention can be produced by recombinant techniques, such that a polynucleotide encoding a peptide, polypeptide or protein of the present invention can be included in any one of a variety of expression vectors for expressing a polypeptide (interpreted as providing the library of phage clones; and a phage vector inserted with a naïve gene, claims 4 and 5) (col 35, lines 25-30).
Tveita does not specifically exemplify activation-induced deoxycytidine deaminase (AID); and polymerase eta (claim 1, in part); and forming gapped, double stranded DNA vectors that expose the naïve IgV gene or the gene encoding the VH and/or VL of the native IgV gene (claims 7 and 12, in part); and double-stranded phage vectors that further comprise one or more restriction enzyme sites (claim 13).
Regarding claim 1 (in part), Liu teaches reagents and methods useful for targeted editing of nucleic acids including editing a single site within the genome of a cell or subject (Abstract). Liu teaches a base editor is a protein (e.g., a fusion protein) comprising a nucleic acid programmable DNA binding protein (napDNAbp) fused to a cytidine deaminase, wherein the base editor can be fused to a uracil binding protein (UBP), such as a uracil DNA glycosylase (UDG); and/or fused to a nucleic acid polymerase (NAP) domain including translesion DNA polymerase, such that the base editor comprises a napDNAbp, a cytidine deaminase and a nucleic acid polymerase (e.g., a translesion DNA polymerase), wherein exemplary translesion polymerases include polymerase eta (interpreted as comprising AID and pol eta; and interpreting contacting the library of nanobodies with the fusion protein to diversify and further diversify the library resulting in somatic hyper-mutation, claim 1) (col 9, lines 29-41; and col 67, lines 35-41). Liu teaches that various methods for making the amino acid substitutions (mutations) provided herein are well known in the art, and are provided by, for example, Green and Sambrook, 4th ed., Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2012) (interpreting contacting the library of phage clones with the fusion protein to diversify and further diversify the library, claim 1) (col 10, lines 44-49).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to contact the nanobodies exemplified by Tveita with the fusion proteins disclosed by Liu with a reasonable expectation of success in generating mutations in a sequence of interest to identify packages that express an antibody having specificity for a target antigen; to produce viral particles that contain membrane associated proteins expressed by the transfected packaging cell line; and/or for in vitro simulation of affinity maturation.
Tveita does not specifically exemplify forming gapped, double stranded DNA vectors that expose the naïve IgV gene or the gene encoding the VH and/or VL of the native IgV gene (claims 7 and 12); and double-stranded phage vectors that further comprise one or more restriction enzyme sites (claim 13).
Regarding claims 7, 12 (both in part) and 13, Kramer teaches a simple and efficient method is described to introduce structurally pre-determined mutations into recombinant genomes of filamentous phage M13, wherein the method rests on gapped duplex DNA (gdDNA) molecules of the phage M13 genome as the key intermediate, such that gdDNA, the (+) and the (shorter) (-) strand carry different genetic markers in such a way, that a rigorous selection can be applied for phage carrying the markers of the (-) strand; and for introduction of the mutation, a synthetic oligonucleotide with partial homology to a target site within the single stranded DNA region is annealed to the gdDNA, such that the oligonucleotide subsequently becomes part of the (-) strand by enzymatic DNA gap filling and sealing, wherein this physical linkage is preserved at the genetic level after transfection of a recipient E. coli strain deficient in DNA mismatch correction, so that the synthetic marker can be selected from the phage progeny independent from its potential phenotype (Abstract). Kramer teaches that gapped duplex DNA (gdDNA) was prepared as schematically outlined in figure 2 and documented in figure 3, wherein RF-DNA of phage M13mp9rev (figure 2, structure I; figure 3, lane 2; see "Materials and Methods" for description of phage) was cleaved with EcoRI and Pvul and the purified large DNA restriction fragment (figure 2, structure II; figure 3, lane 3) was mixed with an excess of single stranded virion DNA of either M13mp9 or M13mp9am16 (figure 2, structure III; figure 3, lane 4; for description of phages see "Materials and M e t h o d s", such that this DNA mixture (figure 3, lane 5 ), was thermally denatured and renatured (total reaction time: 10 min), which resulted in the formation of gapped duplex DNA molecules (figure 2, structure IV) (interpreted as double stranded phage vector containing a gap; denaturing and renaturing; and restriction enzyme sites, claims 7, 12 and 13).
“It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of targeted editing of nucleic acids as exemplified by Liu, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the method of using camelid nanobodies for determining whether a particular antibody molecule interacts with a target ligand as disclosed by Tveita; and the method of introducing structurally pre-determined mutations into recombinant genomes as taught by Kramer to include the fusion proteins comprising sequences encoding AID and polymerase eta as taught by Liu with a reasonable expectation of success in screening a library of nucleic acid sequence that encode VHH sequences or nanobody sequences that specifically bind to target proteins; in identifying VHH antibodies that target and/or modulate enzymes responsible for antibody diversification and affinity maturation; and/or in identifying fusion proteins that target tumor associated macrophages.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Conclusion
Claims 1, 4, 5, 7, 12 and 13 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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