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 .
Priority
This application is a 371 of PCT/US2022/018386 filed 03/01/2022. The claims are all examined using the earlier filing date of 03/01/2022.
Claim Status
Claims 1-12, 18, 32-36, 66 and 83 are pending. Claims 13-17, 19-31, 37-65, 67-82, 84-87 were cancelled prior to examination. Claims 1, 18, 36, 66, and 83 independent claims.
Election/Restrictions
Claim 83 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected method of treating a patient having severe COVID-19, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 07/01/2026, however Applicant’s belief that “multiple groups can be searched and examined together without burden” is not persuasive. The method of generating a cDNA-protein conjugate and the method of treating disease do not relate to single inventive concept and there would be a serious search burden in examining the unrelated concepts.
Applicant has elected Group I inventions relating to the cDNA-protein conjugates. As such, claims 1-12, 18, 32-36, and 66, are under examination.
Drawings
The drawings are objected to because the use of improperly demarcated trademarks has been noted in this application. Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner that might adversely affect their validity as trademarks. See MPEP §608. 01(v). Examples of such improperly demarcated trademarks “HaloTag”, which appears in at least Figs. 1, 3, and 7. Examiner notes that the provided examples are not meant to be a complete list of improperly demarcated trademarks found in the present drawings. Applicant should review the entire specification and correct all instances of improperly demarcated trademarks.
Appropriate corrections required. Each letter of a trademark should be capitalized or otherwise the trademark should be demarcated with the appropriate symbol indicating its proprietary nature (e.g., ™ ©) and accompanied by generic terminology. Applicants may identify trademarks using the USPTO's trademark database. Trademark Electronic Search System (TESS), on the Internet at https: / / www.uspto.gov7trademarks-application-process/search-trademark-database
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
The specification references the color red in the description of Figures 2, 3, 5
Specification
The specification is objected to because the use of improperly demarcated trademarks has been noted in this application. Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner that might adversely affect their validity as trademarks. See MPEP §608. 01(v). 9. Examples of such an improperly demarcated trademarks “HaloTag”, “SNAP-tag”, and “Illumina” which appears in the present specification in paragraphs [0006], [0010], and [0021], respectively. Examiner notes that the provided examples are not meant to be a complete list of improperly demarcated trademarks found in the present specification. Applicant should review the entire specification and correct all instances of improperly demarcated trademarks. Appropriate corrections required. Each letter of a trademark should be capitalized or otherwise the trademark should be demarcated with the appropriate symbol indicating its proprietary nature (e.g., ™, ©, ®) and accompanied by generic terminology. Applicants may identify trademarks using the USPTO's trademark database. Trademark Electronic Search System (TESS), on the Internet at https://tmsearch.uspto.go
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.
Claim 2 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.
Claim 2 recites “wherein the vector library is nicked prior to step (a).” The specification’s only support for this limitation appears at paragraph [0008] and [0060], each of which states, in identical language: “In a specific embodiment, the vector library is nicked prior to step (a).” No other paragraph of the specification uses the term “nick”, “nicked”, or “nicking” in any context. This bare recitation does not satisfy the written description requirement for the following reasons:
There is no structural definition of what “nicked” requires. The specification does not disclose which strand of the vector is nicked, how many nicks are introduced, or by what means (e.g., a specific nicking endonuclease, recognition sequence, or any other nicking chemistry). By contrast, the specification’s companion embodiment, vector linearization, is given a corresponding structural element throughout the specification and claims (e.g., claim 3’s endonuclease site for vector linearization, [0053] “the vector further comprises an endonuclease site for vector linearization”; [0102]/[0200] disclosing “a homing endonuclease (I-SceI) site for plasmid linearization”). No analogous structural element (e.g., nickase recognition site) is disclosed anywhere in the specification for a nicking embodiment.
There is no disclosure of position within the vector. Unlike the elements of claim 1(a), which are expressly positioned “in the 5’ to 3’ direction” relative to one another (transcriptional start site, barcode, reverse transcription primer binding site, RBS, fusion protein coding sequence), the specification does not disclose where on the vector the nick is introduced, e.g., upstream or downstream of the transcription start site, within the barcode, or elsewhere.
There are no working examples. The Examples section of the specification (Examples 1-3) describe, in detailed protocol form, linearization of the pDEST-MIPSA vector using the I-SceI restriction endonuclease prior to in vitro transcription (see [0085], [0183]). No corresponding protocol, reagent, or experimental result is provided anywhere in the specification for a nicked vector library. The specification’s only reduction to practice of a pre-transcription template-modification step is linearization, not nicking.
There is no disclosed function or result. The specification does not explain what purpose or effect nicking the vector library serves, e.g., whether it is intended to terminate run-off transcription at a defined point (as full linearization is understood to do), to relax vector topology, to facilitate some other downstream step, or to achieve some other stated goal. Absent any such explanation, the specification does not demonstrate that the inventors possessed an operative embodiment employing this feature, as opposed to having speculatively identified nicking as a label for an undeveloped alternative to the fully supported linearization embodiment.
A mere naming of a claimed feature, without any accompanying description of the structure, means of achieving it, or function it performs, does not necessarily satisfy the written description requirement where the feature is not so well understood in the art that its bare recitation alone would convey to a person of ordinary skill that the inventor possessed the claimed embodiment. See MPEP 2163(II)(A)(3)(a) (the written description requirement may not be satisfied by “merely a wish or plan for obtaining” the claimed invention and actual reduction to practice or definition of the invention sufficiently to show possession is required); Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). Here, the specification’s identical, isolated, one-sentence recitations at [0008] and [0060], unaccompanied by any structural detail, positional information, working examples, or disclosed function, do not reasonably convey that the inventors had possession of a nicked vector library embodiment of the claimed method, as distinguished from the fully described and exemplified linearized vector library embodiment.
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.
Claim 7, 9-10, 12, and 32 – 35 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 7 recites the limitation "the protein of interest" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 9 and 10 contains the trademark/trade name “HaloTag”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe haloalkane dehalogenase and, accordingly, the identification/description is indefinite.
Claim 12 contains the trademark/trade name “SNAP-tag”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe O6-alkylguanine-DNA alkyltransferase and, accordingly, the identification/description is indefinite.
Claims 32-35 each recite the limitation "the library of claim 1" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 1 is a method claim. It never recites forming, producing, or yielding “a library”, it recites transcribing, reverse transcribing, and translating steps ending in the ligand binding the tag. There is no “thereby forming a library” clause or product recitation anywhere in claim 1 that “the library of claim 1” could be a reference back to.
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 66 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. Claim 66 depends from claim 50 which has been cancelled by the Applicant. 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
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4-12, 18, 32-36, and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Church et al. (US 2017/0107566 A1, published Apr. 20, 2017, on IDS).
Church discloses two related embodiments for producing DNA-barcoded proteins, which the Office finds obvious to combine.
In the first embodiment, Church discloses barcoded linear DNA templates pooled and in vitro transcribed (see Church [0137]), wherein “the barcoded templates contain a polymerase (e.g., T7 polymerase) promoter, and mRNAs are synthesized from the barcoded DNA templates by in vitro transcription” (see Church [0008]), introduced by performing PRC with barcoded primers (see Church [0137]), and reverse transcription… performed using universal primers, and the cDNA sequence are complementary upstream to a ribosome binding site of the barcoded template (see Church [0009]). This embodiment further discloses forming mRNA-cDNA hybrids by incubating mRNA with a 5’-acrydite and desthiobiotin-modified primer, dNTPS, and reverse transcriptase, followed by in vitro expression to generate protein-ribosome-mRNA-cDNA (PRMC) complexes (see Church [0137]).
In a second embodiment, Church discloses a method for attaching a barcode to a polypeptide, comprising the steps of providing a DNA template comprising an enzyme ligand at its 5’ end, providing fusion protein comprising an enzyme tag specific for the ligand, and allowing the enzyme to covalently bind the ligand to produce a polypeptide comprising a barcode (see Church [0010]), wherein an enzyme tag is selected from the group consisting of one or more of HaloTag, CLIP tag, SNAP tag, and the like (see Church [0011]). Church further discloses the specific conjugation chemistry, a HaloTag ligand was conjugated to the primer (see Church [0141]), and HaloTag engineered fusion protein (see Church [0086], Fig. 1).
In regards to claims 1 and 66, Church discloses each limitation of claim 1 as follows:
(a) “transcribing a vector library into messenger ribonucleic acid (mRNA), wherein the vector library encodes a plurality of proteins and wherein each vector of the vector library comprises in the 5' to 3' direction:(i) a polymerase transcriptional start site;(ii) a barcode;(iii) a reverse transcription primer binding site;(iv) a ribosome binding site (RBS); and(v) a nucleotide sequence encoding a fusion protein comprising (1) a polypeptide tag and (2) a protein, wherein the polypeptide tag specifically binds a ligand.” Church teaches methods for generating barcoded protein complexes using nucleic acid templates, reverse transcription, and in vitro translation systems for massively parallel protein analysis (see Church [0005]-[0007], [0086]). Church teaches providing a linear barcoded DNA templates encoding proteins of interest. Church teaches that random or synthesized barcoding sequences may be introduced to the 5’ end of protein open reading frames (ORFs) by PCR (see Church [0086]). Church further teaches templates containing transcriptional promoter sequences and subsequent in vitro transcription to generate barcoded mRNA templates (see Church [0006]-[0007], [0137]). One of ordinary skill in the art would have understood such expression templates to include conventional elements required for transcription and translation, including promoter sequences, ribosome binding sites, and reverse transcription primer binding regions necessary to generate the disclosed mRNA-cDNA hybrid molecules, using vectors such as those presented in Figs. 1 and 10. Church further teaches nucleotide sequences encoding fusion proteins comprising proteins of interest fused to HaloTag polypeptide tag, wherein the protein of interest and the tag are present in a single polypeptide (see Church [0086]).
Church discloses reverse transcribing the 5’ end of the mRNA using a primer that binds upstream of the RBS (see Church [0009]). Church further teaches using special primers conjugated with the ligand that specifically binds the polypeptide tag. “A HaloTag ligand was conjugated to the primer by incubating the amino modified oligo… and ligand” (see Church [0141]). Church discloses forming a barcode-bearing cDNA by reverse transcription with a modified primer and separately discloses that a HaloTag ligand conjugated primer is used to generate a barcoding DNA product (see Church [0009], [0137], [0141]). It would have been obvious to a person having ordinary skill in the art at the time of filing to substitute the acrydite/desthibiotin reverse transcription primer with the HaloTag ligand conjugated primer, since Church already demonstrates that RT primers positioned downstream of an RBS on a barcoded template generate barcode-bearing DNA and that oligonucleotide primers can be conjugated to a HaloTag ligand by the identical succinimidyl ester conjugation chemistry disclosed in para. [0141]. This is a combination of prior art elements according to a known method to yield a predictable result. See MPEP 2143(A); KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007). Therefore, Church renders obvious “(b) reverse transcribing the 5' end of the mRNA using a primer that binds upstream of the RBS, wherein the primer is conjugated with the ligand that specifically binds the polypeptide tag of the fusion protein, and wherein a complementary deoxyribonucleic acid (cDNA) is formed comprising the ligand, primer and barcode.”
Church discloses that HaloTag mediates an efficient covalent conjugation to a HaloTag ligand modified double stranded DNA and describes translation of barcoded mRNA-cDNA hybrids in an in vitro system (see Church [0086], [0137]). Combining Church’s ligand conjugated primer/cDNA (as modified above) with Chruch’s discloses in vitro translation step would predictably result in the ligand of the cDNA binding the polypeptide tag of the translated fusion protein, consistent with the covalent-conjugation mechanism Church expressly attributes to the HaloTag/HaloTag ligand pairs (see Church [0086]). A person of ordinary skill would have been motivated to combine these two embodiments of Church to streamline Church’s own two-step process, separately barcoding by PCR-based ligand primer conjugation and separately generating barcoded cDNA by reverse transcription upstream of an RBS, into a single coupled transcription/reverse-transcription/translation workflow, with a reasonable expectation of success given that Church discloses each constituent step and reagent individually and applies both toward the same stated goal of producing barcoded proteins for massively parallel analysis (see Church [0005], [0009]-[0010], [0141]). Thus, Church makes obvious “(c) translating the mRNA, wherein the ligand of the cDNA binds the polypeptide tag of the fusion protein” and discloses every aspect of claim 1.
In regards to claim 2, Church does not expressly disclose that “the vector library is nicked prior to step (a),” however, one of ordinary skill in the art would recognize that nicking the non-template DNA strand prior to in vitro transcription using T7 polymerase was a known, art-recognized, controllable variable affecting the transcriptional output of that template.123
Church discloses the use of T7 promoter driven barcoded vector from which mRNA is in vitro transcribed (see Church [0008], [0137]). It would have been obvious to a person having ordinary skill in the art at the time of filing to introduce a nick into Church’s vector prior to transcription as part of routine optimization of Church’s assay. Nick presence and position relative to a transcribed sequence was known controlled parameter affecting the transcription output of a T7 driven template1, and a person of ordinary skill in the art optimizing Church’s system would have had reason to employ nicking as one of a finite number of known, available template modifications for controlling transcriptional output, with a reasonable expectation of success given the well-characterized nature of this effect in the art.
Claim 2 recites no structural position, target strand, or functional result stemming from the recited nick. The selection of nicking from a finite, known set of predictable template-modification techniques, for the general and recognized purpose of modulating transcriptional output during optimization of an in vitro transcription based assay is obvious.
In regards to claims 4 and 5, Church discloses that “a barcode is added to the original barcoding DNAs of the polypeptides using PCR, which compatible with standard sample barcoding protocols used in next-generation sequencing methods” (see Church [0019]). A barcode introduced and amplified by PCR necessarily is bounded by primer binding sites for the PCR primers used to introduce/amplify it.
In regards to claims 6, Church discloses “ human protein genes were sub-cloned into pIRESCHaloFlagHis or pIRES-CHaloFlagHis-Gateway containing an internal ribosome entry site (IRES) for in vitro protein synthesis with a human IVT kit (Thermo Scientific)” (see Church [0140]), directly disclosing the RBS comprises an internal ribosome entry site.
In regards to claim 7, Church discloses “GPCRs were expressed as a fusion protein bearing an N-terminal Flag and a HA tag and a Halo Tag,” (see Church [0139]), explicitly teaching “the polypeptide tag is fused to the N-terminal end of the protein of interest.”
In regards to claims 8-10, Church discloses HaloTag as the enzyme tag (see Church [0011]) and HaloTag’s identity as haloalkane dehalogenase is of record via Church’s citation to Los, G.V. “HaloTag: a novel protein labeling technology” (see Church [0086], Ref. 11), which discloses HaloTag as an engineered haloalkane dehalogenase. The sequence of SEQ ID NO: 22 corresponds with this engineered enzyme (see Church SEQ ID NOS: 2-7).
In regards to claim 11, Church teaches using DNA barcodes with HaloTag Ligand (see Church Fig. 1, [0027]). The HaloTag ligand is known in the art to have the chemical structure of Formula I. In addition, modified HaloTag ligands comprising alternative reactive functional groups, including iodoacetamide, Amine O2 ligan, succinimidyl ester O2 ligand corresponding to Formulas II-IV, were commercially available from Promega Corporation prior to the effective filing date of the present application, as evidenced by the “HaloTag® Ligand Building Blocks” website screen capture from Jan. 19, 2021, obtained from WayBackMachine (web.archive.org). Church further teaches using succinimidyl ester conjugation to join HaloTag ligand to DNA oligos containing barcodes (see Church [0141]).
One of ordinary skill in the art would have been motivated to use such commercially available variants of the HaloTag ligand in the methods of Church in order to enable conjugation to a variety of molecules, modify reactivity, or tailor physiochemical properties, since these ligands were specifically designed for use with HaloTag systems and were known to perform the same core function of covalent labeling.
Accordingly, substituting the HaloTag ligand of Church with any of the known, commercially available HaloTag ligand variants represents the use of known alternatives for their intended purpose and would have been obvious to one of ordinary skill in the art.
In regards to claim 12, Church discloses “an enzyme tag is selected from the group consisting of one or more of Halo Tag, CLIP tag, SNAP tag and the like” (see Church [0011]). It would have been obvious to one of ordinary skill to substitute Church’s exemplified HaloTag/HaloTag-ligand pair with Church’s expressly named alternative, SNAP tag, and its cognate SNAP-ligand, as a simple substitution of one known art recognized equivalent for another to obtain predictable results. See MPEP 2143(I)(B).
In regards to claims 18 and 36, these claims recite substantially the same protein-DNA conjugate structure produced by the method of claim 1; the rejection of claim 1 applies with equal force to the resulting product-by-process/composition claims (see Church [0086], [0141]). Furthermore, Church teaches a library comprising “a DNA comprising a barcode, wherein the DNA is conjugated with a ligand that specifically binds a polypeptide tag; and a fusion protein comprising the polypeptide tag and a protein of interest, wherein the ligand is covalently bound to the polypeptide tag” (see Church Fig. 1).
In regards to claims 32-35, Church teaches embodiments “directed to novel methods for detecting interactions, e.g., protein-protein interactions, protein-nucleic acid interactions, protein-small molecules interaction, binding affinities and the like” (see Church [0044]). These include immunoprecipitation methods comprising the steps of perform a pull-down assay using a library of barcoded DNA covalently bound to a fusion protein (see Church Fig. 1 [0144]-[0145]), Church discloses that selected scFvs were fused to a C-terminal streptavidin binding peptide and captured by streptavidin coated magnetic beads to pull down bound human protein fusions with a HaloTag (see Church [0094]-[0095]). Church further disclosing interaction confirmation by immunoprecipitation (see Church [0096]).
Claim(s) 1-12, 18, 32-36, and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Church et al. (US 2017/0107566 A1, published Apr. 20, 2017, on IDS) as applied to claims 1-2, 4-12, 18, 32-36, and 66 above, and further in view of Brunelle and Green (“In Vitro Transcription from Plasmid or PCR-amplified DNA”, Methods in Enzymology, Chap. 5, pgs. 101-114, 2013).
In regards to claim 3, Church teaches all of the limitations of claim 1 for which the claim depends, but Church does not expressly disclose that the vector library further comprises an endonuclease site for vector linearization or that the vector library is linearized prior to step (a).
Brunelle teaches this limitation. Brunelle discloses that bacteriophage RNA polymerases are a standard tool for the synthesis of both short and long RNA molecules by in vitro transcription from DNA templates, expressly identifying T7 RNA polymerase, among others, for this purpose. Brunelle discloses that a practitioner should linearize plasmid DNA by restriction enzyme digestion using an enzyme that cuts just downstream of the transcript you want to produce, as an alternative to generating a PCR reaction product consisting of the T7 promoter followed by the sequence of the transcript to be produced, and further discloses that this linearization is performed prior to the in vitro transcription reaction, instruction the practitioner to prepare the DNA template for the transcription reaction, using either restriction enzyme digested plasmid or PCR amplified DNA before carrying out the transcription step. Brunelle further discloses that this process is adapted from Milligan et al. (“Synthesis of small RNAs using T7 RNA polymerase” Methods in Enzymology 180 (1989), confirming that restriction site-based linearization of a plasmid template positioned downstream of the transcribed sequences, was a foundational, well-established practice in the art well before the instant application.
It would have been obvious to a person having ordinary skill in the art at the time of filing to modify Church’s T7-promoter vector to include a restriction endonuclease recognition site positioned downstream of the barcode, RT-primer binding site, RBS, coding sequence elements of claim 1, and to linearize the vector at that site prior to in vitro transcription, as taught by Brunelle, because Brunelle establishes that linearizing a circular T7-promoter bearing plasmid template by restriction digest was a standard, foundational technique for this exact type of reaction. A person of ordinary skill would have been motivated to incorporate this well-known linearization technique into Church’s system to obtain a more reliable, physically defined termination point for in vitro transcription, with a reasonable expectation of success given Brunelle’s demonstration of the techniques routine, predictable applicability to T7 promoter vectors generally. See MPEP 2143(A).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 9-11, 18, 36 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 114, 115, 138-140, of copending Application No. 19/540,422 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim of the instant application and the co-pending application are directed to a method comprising translating a vector library (claim 1 of the instant application and claim 114 of ‘422) that would yield the composition library of claim 115 of ‘422 or claim 18 or 36 of the instant application. While claim 1 of the instant application is generic in regards to the barcode binding, the methods are patentably distinct from claim 114 of ‘422. The sequence of the HaloTag/polypeptide (SEQ ID NO: 22) is identical between the two applications (claim 10 and claim 138 of ‘422) as are the ligands (claim 11 and claim 139 of ‘422). While claim 9 is equivalent to claim 140 of the ‘422 application, using the sequence to identify the HaloTag and succinimidyl ester haloalkane in place of HaloTag ligand.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/MATTHEW HAROLD RAYMONDA/Examiner, Art Unit 1684
/AARON A PRIEST/ Primary Examiner, Art Unit 1681
1 Roy et al. (“Competition between the RNA Transcript and the Nontemplate DNA Strand during R-Loop Formation In Vitro: a Nick Can Serve as a Strong R-Loop Initiation Site”, Molecular and Cellular Biology, Jan. 2010, p. 146–159)
2 Belotserkovskii et al. (“Transcription blockage by homopurine DNA sequences: role of sequence composition and single-strand breaks”, Nucleic Acids Research, 2013, Vol. 41, No. 3, p 1817-1828)
3 Dynan et al. (“In vitro transcription by wheat germ ribonucleic acid polymerase II: effects of heparin and role of template integrity”, Biochemistry 1979, Vol. 18, No. 21, p 4581-4588)
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