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 .
Applicant previously cancels claims 8-16, 18, 20, 22, 24, 27-37, 39-44, 46-55, 57-66, 69-101, 103-108 and 110-134. Claims 1-7, 17, 19, 21, 23, 25-26, 38, 45, 56, 67-68, 102 and 109 are currently pending and under examination.
Information Disclosure Statement
The Information Disclosure Statements filed June 21, 2022; and July 18, 2024 have been considered.
Specification
The use of the terms AMPure®, MiSeq™ and HiSeq™ (see, Page 97, [00344], Page 99, [00348] and [00350]-[00351], Page 100, [00353]-[00355] and Page 104, [00370]) which are trade names or marks used in commerce, has been noted in this application. The term 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.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 7, 23 and 45 are objected to because of the following informalities”
Claim 7, in line 10, “the DRE is REV”, should read “the DRE is a REV protein”.
Claim 7, in line 7, “TAR RNA stem”, should read “TAR (Trans-Activation Response) RNA stem”.
Claim 7, in lines 6 and 8, “the DRE is TAT”, should read “the DRE is a TAT protein”.
Claim 23, in line 2, “the plurality of barcodes is the normalized to a barcode” should read “the plurality of barcodes is normalized to a barcode input”.
Claim 45, in line 3, “TRS (terminal resolution site)” should read “terminal resolution site (TRS)”.
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 1-7, 19, 21, 23, 25-26, 38, 45, 56, 67, 102 and 109 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 is considered vague and indefinite for the following reasons:
In claim 1, line 9, It is unclear if the information in parentheses, “(or wildtype)”, is intended to be a claim limitation or not.
Claims 2-7, 19, 21, 23, 25-26, 38, 45, 56, 67, 102 and 109 depend from claim 1 and are therefore included in this rejection.
Claim 7 is considered vague and indefinite for the following reasons:
Claim 7 recites the limitations “the A, A’, B, B’, C, C’, D, D’ regions” in lines 2 and 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitations “the TAR RNA stem” in lines 6-7. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the limitations “the UU-rich bulge” in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claim 17 is considered vague and indefinite for the following reasons:
In claim 17, line 9, It is unclear if the information in parentheses, “(or wildtype)”, is intended to be a claim limitation or not.
Claim 19 is considered vague and indefinite for the following reasons:
In claim 19, in lines 2-4, the terms “waiting a sufficient amount of time” is unclear and confusing. It is unclear as to what the amount of time one needs to wait for it to be sufficient ?
Claim 21 is considered vague and indefinite for the following reasons:
In claim 21, line 5, It is unclear if the information in parentheses, “(amplicon)”, is intended to be a claim limitation or not.
Additionally, claim 21 recites the limitations “the amplicon” in lines 6-7. There is insufficient antecedent basis for this limitation in the claim.
Claim 23 is considered vague and indefinite for the following reasons:
Claim 23 recites the limitations “the amplicon” in line 4. There is insufficient antecedent basis for this limitation in the claim.
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 1-2, 5-6, 17, 19, 21, 25, 38, 45, 56 and 67 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Esteves et al. (U.S. Patent Application Publication US 2018/0265863, published September 20, 2018), cited on the IDS filed June 21, 2022.
Regarding claim 1, Esteves teaches a method of identifying the strength of one or more unique regulatory elements (URE) having conformational effect on a transcribable reporter sequence (Pages 10-11, [0107], Page 9, [0092], Page 7, [0079], Page 19, [0163] and Figure 1). Esteves teaches expressing a plurality of synthetic nucleic acids in a population of cells (Page 1, [0010], Page 2, [0014]-[0015], Page 4, [0052] and Pages 7-8, [0079]-[0080]). Esteves teaches a first plurality of synthetic nucleic acids each comprising a unique regulatory element (URE) (Pages 10-11, [0107], Page 9, [0092] Pages 5-6, [0065], Page 7, [0079], Page 19, [0163]). Esteves teaches URE comprises a nucleic acid sequence containing at least one discrete regulatory element (DRE), and the DRE is a control, or wild type, continuous nucleic acid sequence or a control discontinuous nucleic acid sequence associated with a plurality of unique barcodes corresponding with the at least one DRE (Page 1, [0005]-[0007], Page 5, [0056] and [0062], Page 6, [0065], Page 19, [0163] and Page 8, [0086]). Esteves teaches each barcode is between 12-35 nucleotides in length and has a GC content between 25-65% (Page 1, [0005]-[0006] and [0009], Page 5, [0058] and Table 1). Esteves teaches the DRE is conformationally positioned in a preselected manner relative to a nucleic acid encoding a transcribable reporter sequence (Page 8, [0085] and [0088], Pages 15-16, [0126] and Page 19, [0159]. Esteves teaches the URE contains a promoter (Page 7, [0079], Page 8, [0088], and Page 9, [0096]-[0098]). Esteves teaches a second plurality of synthetic nucleic acids comprising a URE that further comprises a change in the conformation of said at least one DRE of a1. (Pages 10-11, [0107], Page 9, [0092] Pages 5-6, [0065], Page 7, [0079], Page 19, [0163]). Esteves teaches relative to the transcribable reporter sequence wherein the conformationally changed DRE is associated with a plurality of unique barcodes different than in a1 (Pages 5-6, [0065], Page 20, [0165]-[0167] and Page 22, [0184]). Esteves teaches wherein each barcode is between 12-35 nucleotides in length and has a GC content between 25-65% (Page 1, [0005]-[0006] and [0009], Page 5, [0058] and Table 1). Esteves teaches determining the expression frequency of each of the plurality of corresponding barcodes in step a1. and step a2. (Page 2, [0016] and [0018], Page 19, [0163] and Page 20, [0166]). Esteves teaches changing in a predetermined manner the conformation of at least one of the corresponding plurality of synthetic nucleic acids' DRE relative to the transcribable reporter sequence (Page 2, [0018], Pages 5-6, [0065], Page 4, [0053], Page 7, [0076], Page 11, [0113], Page 13, [0119], Pages 15-16, [0126], Page 19, [0163] and Page 20, [0166]). Esteves teaches determining the expression frequency of the at least one corresponding plurality of (c) (Page 2, [0018], Pages 5-6, [0065], Pages 6-7, [0073], Page 19, [0159], [0161] and [0163], Page 20, [0166], and Page 21, [0180]-[0181]). Esteves teaches comparing the expression frequency of a1 and a2 to determine the effect of the conformation change on the transcribable reporter sequence expression (Page 2, [0018], Page 3, [0038] and [0040]-[0041], Pages 5-6, [0065], Page 19, [0163] and Page 20, [0166]).
Regarding claim 2, Esteves teaches the plurality of synthetic nucleic acids is expressed a population of cells using a population of viral vectors (Page 7, [0076] and Page 5, [0088]).
Regarding claim 5, Esteves teaches at least one DRE is present in a terminal repeat (TR) (Page 7, [0076]-[0077] and Pages 8-9, [0090]-[0093].
Regarding claim 6, Esteves teaches the viral vector is a parvovirus, a lentivirus, or an adenovirus (Abstract, Page 1, [0005], Page 4, [0048], Page 8, [0083], Page 9, [0092], Page 19, [0164] and Pages 22-23, [0195]).
Regarding claim 17, Esteves teaches a method of identifying the strength of one or more unique regulatory elements (URE) having conformational effect on a transcribable reporter sequence (Pages 10-11, [0107], Page 9, [0092], Page 7, [0079], Page 19, [0163] and Figure 1). Esteves teaches expressing a plurality of synthetic nucleic acids in a population of cells (Page 1, [0010], Page 2, [0014]-[0015], Page 4, [0052] and Pages 7-8, [0079]-[0080]). Esteves teaches a first plurality of synthetic nucleic acids each comprising a unique regulatory element (URE) (Pages 10-11, [0107], Page 9, [0092] Pages 5-6, [0065], Page 7, [0079], Page 19, [0163]). Esteves teaches URE comprises a nucleic acid sequence containing at least one discrete regulatory element (DRE), and the DRE is a control, or wild type, continuous nucleic acid sequence or a control discontinuous nucleic acid sequence associated with a plurality of unique barcodes corresponding with the at least one DRE (Page 1, [0005]-[0007], Page 5, [0056] and [0062], Page 6, [0065], Page 19, [0163] and Page 8, [0086]). Esteves teaches each barcode is between 12-35 nucleotides in length and has a GC content between 25-65% (Page 1, [0005]-[0006] and [0009], Page 5, [0058] and Table 1). Esteves teaches the DRE is conformationally positioned in a preselected manner relative to a nucleic acid encoding a transcribable reporter sequence operatively linked to a promoter (Page 8, [0085] and [0088], Pages 15-16, [0126] and Page 19, [0159], Page 7, [0079], Page 8, [0088] and Page 9 [0096]-[0098]). Esteves teaches a second plurality of synthetic nucleic acids comprising a URE that further comprises a change in the conformation of said at least one DRE of a1. (Pages 10-11, [0107], Page 9, [0092] Pages 5-6, [0065], Page 7, [0079], Page 19, [0163]). Esteves teaches relative to the transcribable reporter sequence wherein the conformationally changed DRE is associated with a plurality of unique barcodes different than in a1 (Pages 5-6, [0065], Page 20, [0165]-[0167] and Page 22, [0184]). Esteves teaches wherein each barcode is between 12-35 nucleotides in length and has a GC content between 25-65% (Page 1, [0005]-[0006] and [0009], Page 5, [0058] and Table 1). Esteves teaches generating a library of plasmids or expression vectors by inserting the plurality of synthetic nucleic acids into a plurality of plasmids or expression vectors (Page 2, [0016], Page 3, [0029], Page 6, [0071], Page 8, [0088] and Pages 19-20, [0163]-[0167]). Esteves teaches resulting plasmid or expression vector comprises a single synthetic nucleic acid (Page 1, [0007], Page 5, [0056] and [0062] and Page 20, [0167] and [0171]). Esteves teaches introducing the library of plasmids or expression vectors of step (b) into a population of cells (Page 2, [0016], [0084]-[0085] and Page [0088]). Esteves teaches determining the expression frequency of each of the plurality of corresponding barcodes in step a1 and step a2 (Page 2, [0016] and [0018], Page 19, [0163] and Page 20, [0166]). Esteves teaches comparing the expression frequency of a1 and a2 to determine the effect of the conformation change on the transcribable reporter sequence expression (Page 2, [0018], Page 3, [0038] and [0040]-[0041], Pages 5-6, [0065], Page 19, [0163] and Page 20, [0166]).
Regarding claim 19, Esteves teaches comprising at least one of the step of, after step (a), waiting a sufficient amount of time for expression of the plurality of synthetic nucleic acids in the population of cells, or the step of, after step (c), waiting a sufficient amount of time for expression of the library of plasmids or expression vectors of step (b) (Page 2, [0018], Page 20 [0167]-[0168] and Page 21, [0173]).
Regarding claim 21, Esteves teaches determining includes the steps of obtaining mRNA from the population of cells (Page 10, [0105] and Page 13, [0120]). Esteves teaches synthesizing cDNA from the mRNA of step a (Page 11, [0112] and Page 19, [0157]). Esteves teaches amplifying a region of nucleic acids from the cDNA of step (b) (Page 2, [0015]-[0016], Page 3, [0029], Page 19, [0157] and Pages 21-22, [0183]). Esteves teaches measuring the expression frequency of each of the plurality of barcodes in the amplicon of step (c) (Page 2, [0016] and [0018], Page 19, [0163] and Page 20, [0166]).
Regarding claim 25, Esteves teaches at least one DRE is a discontinuous DRE (Pages 5-6, [0065]).
Regarding claim 38, Esteves teaches the URE comprises at least DRE selected from the group consisting of: a promoter, a transcription factor binding site, an enhancer, a silencer, a boundary control element, an insulator, a locus control region, a response element, a binding site, a segment of a terminal repeat, a responsive site, a stabilizing element, a de-stabilizing element, and a splicing element (Page 7, [0076] and [0079], Page 9, [0095]-[0096], Page 10, [0105], Page 12, [0115] and Page 11, [0113]).
Regarding claim 45, Esteves teaches the viral vector is an AAV vector and the at least a part of a terminal repeat (TR) inverted terminal repeat (ITR) (Page 7, [0076]).
Regarding claim 56, Esteves teaches the barcode contains at least one of each: adenine, thymine, guanine, and cytosine (Page 1, [0005]).
Regarding claim 67, Esteves teaches the synthetic nucleic acid comprises at least one unique molecular identifier (UMI) and at least one unique primer annealing sites (UPAS) tag (Page 1, [0009], Page 3, [0029], Page 6, [0071] and Page 21, [0172]).
Esteves teaches each and every limitation of claims 1-2, 5-6, 17, 19, 25, 38, 45, 56 and 67, therefore Esteves anticipates claims 1-2, 5-6, 17, 19, 25, 38, 45, 56 and 67.
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.
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 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Esteves et al. (U.S. Patent Application Publication US 2018/0265863, published September 20, 2018), cited on the IDS filed June 21, 2022, as applied to claims 1-2, 5-6, 17, 19, 21, 25, 38, 45, 56 and 67 above, in view of Engelhardt et al. (U.S. Patent Application Publication US 2008/0226600, published September 18, 2008), cited on the IDS filed June 21, 2022.
Regarding claim 3, Esteves teaches the DRE as discussed above.
Regarding claim 4, Esteves teaches the change in conformation is made by the addition, deletion, or substitution of one or more nucleic acids (Page 6, [0069]-[0070] and [0072], Page 11, [0113] and Page 13, [0119]).
Esteves does not teach or suggest the DRE is proximal to or within a Holliday junction and a change in at least one of the Holliday junctions is made.
Engelhardt teaches using various AAV vectors with various conformations of ITRs (Page 6, [0041], Page 20, [0167], Pages 20-21, [0170] and Page 27, [0210]). Engelhardt teaches the DRE is proximal to or within a Holliday junction and a change in at least one of the Holliday junctions is made (Page 18, [0157], and Page 22, [0176]). Engelhardt teaches having the DRE being proximal or within the Holliday Junction aids in viral integration and Holliday junctions have been shown to play critical roles in directing homologous recombination in bacteria (Page 18, [0157]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified the teachings of Esteves with the teachings of Engelhardt, having the DRE be proximal to or within a Holliday junction and a change in at least one of the Holliday junctions is made. Having the DRE being proximal or within the Holliday Junction aids in viral integration and Holliday junctions have been shown to play critical roles in directing homologous recombination in bacteria as taught by Engelhardt (Page 18, [0157]).
Claims 7 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Esteves et al. (U.S. Patent Application Publication US 2018/0265863, published September 20, 2018), cited on the IDS filed June 21, 2022, as applied to claims 1-2, 5-6, 17, 19, 21, 25, 38, 45, 56 and 67 above, in view of Wilson et al. ( U.S. Patent Application Publication US 2018/0265863, published September 20, 2018), cited on the IDS filed June 21, 2022.
Regarding claim 7, Esteves teaches the parvovirus is an adeno-associated virus as discussed above.
Regarding claim 26, Esteves teaches the DRE as discussed above.
Esteves does not teach or suggest the discontinuous DRE comprises a portion of the DRE located 5' of the transcribable reporter sequence, and a portion of the DRE located 3' of the transcribable reporter sequence.
Esteves does not teach or suggest the change in conformational is in at least one of the A, A', B, B', C, C', D, D' regions.
Wilson teaches using AAV viral vector stereotypes and AAV mediated delivery of a transgene to host cells (Abstract and Page 2, [0016]). Wilson teaches a discontinuous DRE comprises a portion of the DRE located 5' of the transcribable reporter sequence, and a portion of the DRE located 3' of the transcribable reporter sequence (Pages 1-2, [0011]). Wilson teaches the AAV TR sequence is subdivided into A, A', B, B', C, C', D and D' (Page 7, [0090]). Wilson teaches the parvovirus is an AAV (Page 1, [0005] and Page 8, [0096]). Wilson teaches a conformational change in at least A, A', B, B', C, C', D and D' (Page 7, [0090]-[0091] and Page 1, [0005]). Using an AAV TR with a conformational change in at least A, A', B, B', C, C', D and D' allows for studying the biological function of the AAV including DNA replication and site-specific integration (Pages 7-8, [0093] and Page 3, [0041]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Esteves, with the teachings of Wilson, to include a discontinuous DRE comprises a portion of the DRE located 5' of the transcribable reporter sequence, and a portion of the DRE located 3' of the transcribable reporter sequence as well as include a parvovirus being the AAV the conformational change in at least A, A', B, B', C, C', D and D'. This would allow for studying the biological function of the AAV including DNA replication and site-specific integration, which can be further used for gene therapy as taught by Wilson (Page 1, [0007], Pages 7-8, [0093], Page 3, [0041] and Example 4).
Claims 68, 102 and 109 are rejected under 35 U.S.C. 103 as being unpatentable over Esteves et al. (U.S. Patent Application Publication US 2018/0265863, published September 20, 2018), cited on the IDS filed June 21, 2022, as applied to claims 1-2, 5-6, 17, 19, 21, 25, 38, 45, 56 and 67 above, in view of Roberts et al. (U.S. Patent Application Publication US 2013/0324440 A1, published December 05, 2013), cited on the IDS filed June 21, 2022.
Regarding claim 68, Esteves teaches each synthetic nucleic acid comprising a URE (Pages 10-11, [0107], Page 9, [0092] Pages 5-6, [0065], Page 7, [0079], Page 19, [0163]). Esteves teaches the URE comprises a nucleic acid sequence containing at least one discrete regulatory element (DRE), and the DRE is a continuous nucleic acid sequence or a discontinuous nucleic acid sequence (Page 1, [0005]-[0007], Page 5, [0056] and [0062], Page 6, [0065], Page 19, [0163] and Page 8, [0086]). Esteves teaches a nucleic acid sequence encoding an open reading frame (Page 19, [0158]). Esteves teaches a nucleic acid sequence encoding a viral vector terminal repeat (TR) (Page 7, [0076]). Esteves teaches a plurality of unique barcodes associated with the at least one DRE, wherein each barcode has a GC content between 25-65% (Page 1, [0005]-[0006] and [0009], Page 5, [0058] and Table 1).
Regarding claims 102 and 109, Esteves teaches a library/population of plasmids and/or viral vectors expressing the plurality of synthetic nucleic acids as discussed above.
Esteves does not teach or suggest explicitly at least 50 synthetic nucleic acids. Esteves does not teach or suggest a population/library of specifically at least 50 viral vectors and/or 50 plasmids.
Roberts teaches designing promotors for expression of genes and identifying transcription regulatory elements (TREs) used to create a viral vector and/or plasmid library and the viral vector being AAV (Abstract and Page 2, [0028], Page 3, [0031] and [0039]). Roberts teaches using synthetic nucleic acids (Page 3, [0034], Pages 3-4, [0040]-[0045] and [0051] and Pages 6-7, [0086]). Roberts further generating a library of plasmids or expression vectors by inserting the plurality of synthetic nucleic acids into a plurality of plasmids or expression vectors (Page 2, [0028] and Claim 4). Roberts teaches using at least 50 synthetic nucleic acids (e.g., artificial nucleic acids, Page 3, [0031]). Roberts teaches a population/library of at least 50 viral vectors and/or 50 plasmids expressing a plurality of synthetic nucleic acids (Page 2, [0029] and Page 3, [0031]). Roberts teaches using these methods allows for gene expression analyses to identify TFREs associated with specific gene expression profiles, allowing for the weighting and ranking of regulatory elements and the development of improved methods of selection (Page 5, [0060]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Esteves with the teachings of Roberts, using at 50 synthetic nucleic acids/viral vectors and/or plasmids to identify regulatory elements. Using these methods allows for gene expression analyses to identify TFREs associated with specific gene expression profiles, allowing for the weighting and ranking of regulatory elements and the development of improved methods of selection as taught by Roberts (Page 5, [0060]).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Esteves et al. (U.S. Patent Application Publication US 2018/0265863, published September 20, 2018), cited on the IDS filed June 21, 2022, as applied to claims 1-2, 5-6, 17, 19, 21, 25, 38, 45, 56 and 67 above, in view of Gill et al. ( U.S. Patent Application Publication US 2017/0369870 A1, published December 28, 2017), cited on the IDS filed June 21, 2022.
Regarding claim 23, Esteves teaches the expression frequency of each of the plurality of barcodes as discussed above.
Esteves does not teach or suggest the expression frequency of each of the plurality of barcodes is the normalized to a barcode input, and wherein the barcode input is each unique barcode content before expression.
Gill teaches barcode trackable genetic variant libraries with modifications within regulatory elements (Abstract, Page 5, [0018]-[0019], Page 6, [0056], Page 9, [0093], Page 17, [0175], Page 21, [0213] and Page 22, [0222]). Gill teaches using plasmids and viral vectors (Page 6, [0056] and Page 8, [0077]). Gill teaches measuring the expression frequency of the barcodes (Page 7, [0070]-[0071]). Gill teaches normalizing the barcode input (Page 31, [0296]). Gill teaches the barcode input is each unique barcode content before expression (Page 1, [0006]-[0007], Page 5, [0019], Page 7, [0074], Page 8, [0086] and Page 29, [0284]). Gill teaches using the disclosed barcoded plasmid libraries, allows for deep-sequencing at one site to track mutational diversity targeted across the remaining portions of the plasmid allowing dramatic improvements in the depth of library coverage (Page 11, [0110]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Esteves with the teachings of Gill, having the expression frequency of each of the plurality of barcodes being normalized to a barcode input, and the barcode input is each unique barcode content before expression. Using these methods allows one to create barcoded plasmid libraries, that allow for deep-sequencing at one site to track mutational diversity targeted across the remaining portions of the plasmid allowing dramatic improvements in the depth of library coverage as taught by Gill (Page 11, [0110]).
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 1-7, 17, 19, 21, 23, 25-26, 38, 45, 56, 67-68, 102 and 109 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-25, 27-79, and 81-87 of copending Application No. 17/787,898 (reference application).
Although the claims at issue are not completely identical, they are not patentably distinct from each other because the preambles are identical as well as it appears that most of the steps of the claims are also identical, so it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform a method of identifying the strength of a URE using a plurality of synthetic nucleic acids and/or library of at least 50 plasmids/expression vectors/viral vectors in a method using those same steps. Therefore, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684