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 .
Election/Restrictions
Applicant's election without traverse of election of Group I (claims 1-13, drawn to a method of identifying a plurality of regions in a genome that binds to a FOXO1-DNA Binding Domain Fusion Protein) in the reply filed on 18 Nov, 2025 is acknowledged.
Claims 14-19 withdrawn from further consideration pursuant to 37 CFR
l.142(b) as being drawn to a nonelected Group II of invention. Accordingly, claims 1-13 are examined herein.
Priority
Acknowledgment is made of applicant's claim for priority based on a US Provisional Application
No. 63/084,098 filed on 28 Sept, 2020.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84(i) states “All views on the same sheet should stand in the same direction and, if possible, stand so that they can be read with the sheet held in an upright position. If views wider than the width of the sheet are necessary for the clearest illustration of the invention, the sheet may be turned on its side so that the top of the sheet, with the appropriate top margin to be used as the heading space, is on the right-hand side.”
In the current case, the view of Figure 1 is sufficiently wide that it is necessary to rotate the sheet. However, the orientation of the Figure on the sheet incorrectly necessitates the rotation of the sheet such that the top of the sheet becomes the left-hand side. A replacement sheet should be provided that reverses the orientation of the Figure such that the top of the sheet becomes the right-hand side after rotation.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the term Cell Signaling Technology ® ([0042]), which is a trade name or a mark 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 1 and 3 are objected to because of the following informalities:
Claim 1 recites “the locations in the genome” in line 9, while line 1 recites “a plurality of regions in a genome”. Claim 12 also recites “at least 1,000 locations in the genome”. There is inconsistent usage of terminology.
Claim 3 does not end in a period. MPEP 608.01(m) states, “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations.”
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 1
Claim 1 is directed to a method of identifying a plurality of regions in a genome…comprising the steps of…”. Thus, the claimed invention is directed to a process, which is one of the statutory categories of invention.
Step 2A, Prong 1
Claim 1 recites “identifying” and “analyzing” which are abstract mental concepts that belong to numerated group (c) of the Abstract Idea Groupings described in MPEP § 2106.04(a)(2): Mental processes - concepts that performed in the human mind (including an observation, evaluation, judgement, opinion). Further, claim 1 recites “identifying…regions in a genome that bind to a FOXO1-DNA-Binding Domain Fusion Protein…”, which recites a natural phenomenon because FOXO1 is a naturally occurring transcription factor that naturally binds to chromatin. Thus, the claim recites at least one judicial exception.
Claims 2-13 are dependent claims of claim 1, and thus recite the judicial exceptions identified for corresponding independent claim.
Step 2A, Prong 2
The additional steps/elements in the claims are next evaluated with considerations set forth in MPEP 2106.5 (a) through (c), (e), and (h). There are no additional elements that reflect an improvement within the technical field; there are no additional elements that apply the natural correlation/phenomena judicial exception to a particular treatment or which utilize a particular machine; there are no additional elements that effect a transformation; and, there are no additional elements that apply the judicial exception in some other meaningful way beyond generally linking it to a field, namely, chromatin immunoprecipitation.
Claim 1 recites additional steps a-e including: obtaining chromatin, sonicating the chromatin, isolating the chromatin, purifying the DNA, amplifying and sequencing the DNA. These steps are merely data gathering steps, and are considered insignificant extra-solution activity. The term “extra-solution activity” can be understood as activities incidental to the primary process or product that are merely a nominal or tangential addition to the claim. As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional. Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978). See MPEP § 2106.05(g). Claim 1 further recites step f “analyzing the sequenced DNA…”, which is another abstract mental step. Therefore, the addition of these elements does not integrate the recited exception into a practical application.
Regarding claims 2 and 3 reciting additional elements including sonication condition and buffer concentration, the specification teaches “…that one skilled in the art would normally sonicate the chromatin preparation” ([0035]), and “a variety of different buffers suitable for use in ChIP can be used” ([0036]).
Regarding claim 4 reciting an additional element of an antibody that binds to FOXO1, the specification teaches “protocols for generating antibodies…may be found in” the art ([0040]).
Regarding claim 5 reciting “wherein the DNA binding Domain is PAX3”, the naturally occurring FOXO1 binds to PAX3 in rhabdomyosarcoma cells, as evidenced by Barr (Oncogene, 2001, 20, 5736-5746) disclosing PAX3-FKHR chimeric proteins (Abstract). Thus, this is merely reciting the natural phenomenon identified in Step 2A.
Regarding claims 6, 7, 8, and 13 reciting wherein the cell is a human cell, a cancer cell, a rhabdomyosarcoma cancer cell, and rodent cells, Collas (Mol Biotechnol, 2010, 45, 87-100) teaches chromatin immunoprecipitation has been extended to a wide range of organisms including mammalian cells (pg. 89, left-column, second paragraph). Claim 6 also recited “the DNA is analyzed by alignment with human genome USCS hg38”, and the specification teaches “those skilled in the art recognize that there are many tools and options for performing the sequence analysis” ([0065]).
Regarding claims 9 and 12 reciting the number of cells from which the chromatin in obtained and the number of locations identified, these additional elements are disclosed by Collas (“ChIP Assays Designed for Small Cell Numbers” and “ChIP-Sequencing” sections).
Regarding claim 10 reciting cross-linking the chromatin, the specification teaches “this may be achieved for any suitable means…suitable protein-DNA cross-linking agents are known those skilled in the art” ([0031]).
Regarding claim 11 reciting wherein one or more genomic regions are a portion of a gene, this is a natural occurring phenomenon whereby FOXO1 binds to genes.
In accordance with MPEP 2106.07(a)(III)(A), the examiner has cited express statements in the specification indicating that the additional elements were sufficiently well-known that the specification does not need to describe the particulars thereof. In other words, the disclosure merely refers to techniques and elements that were known in the art at the time of filling. Thus, these additional elements do not integrate the judicial exception into a practical application.
Step 2B
The steps a-e in claim 1, as previously discussed, amount to insignificant extra-solution activity that is well-understood, routine, and conventional activity in the chromatin immunoprecipitation field, as evidenced by Collas. The step f in claim 1, as previously discussed, refers to another mental step. Therefore, claim 1 does not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The claimed elements recited in dependent claims 2-13 in addition to the judicial exception(s), alone or in combination, do not make an inventive contribution over the methods that were known in the art prior to filling, and they amount to mere observation of the natural phenomenon itself. Thus, claims 2-13 do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
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.
Claim 4 is 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 4 contains the incomplete trademark/trade name “Cell Signaling”, which the specification teaches “Cell Signaling Technology®”, ([0042]). 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 antibody for FOXO1 and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 102
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.
Claims 1-4, and 7-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burgess (US 2006/0292560 A1; Published Date: 28 Dec, 2006) as evidenced by Matsuzaki et al (PNAS, 2003, 100(20): 11285-11290).
Regarding claim 1, Burgess teaches a method of chromosomal immunoprecipitation (ChIP) extended with high-throughput cloning and analysis of transcription factor target loci (Abstract, Fig. 5 and 6, [0093]). Burgess further teaches "while the presently described invention demonstrates its applicability to the discovery of both known and previously undiscovered target loci for the transcription factor p53, it is in no way limited in its utility for this particular transcription factor…other transcription factors covered by the present invention include…FKHR" ([0076]), as evidenced by Matsuzaki that FKHR is the same protein as FOXO1 (Abstract). Therefore, Burgess teaches a method of ChIP to identify target loci ((i.e., a plurality of regions in a genome) of FKHR (i.e., that bind to a FOXO1-DNA binding domain fusion protein). Regarding step a of the instant claim, Burgess teaches “in vivo crosslink fixation” and “Fixed Chromatin Recovery” (Fig. 5) from living cells ([0018]) (i.e., obtaining chromatin from a cell). Regarding step b, Burgess teaches “sonication” of chromatin to customizable fragments lengths (Fig. 5). Regarding step c, Burgess teaches “Direct IP” (Fig. 5) using an antibody that specifically recognize, bind and extract a protein/DNA complex from a bulk population of cross-linked protein/DNA complexes ([0042]) (i.e., using an antibody that binds to FOXO1). Regarding step d of the instant claim, Burgess further “Sequence Acquisition Options” (Figs 5 and 6) wherein DNA fragments collected from immunoprecipitation are amplified using PCR ([0020]) and cloned into vectors for sequencing. Burgess further teaches amplifying and cloning of DNA fragments containing the transcription factor target genes into bacteriophage arms for rapid conventional screening and sequencing (Fig. 9, [0024]). Regarding step f of the instant claim, Burgess further teaches the ChIP method concludes with “Import Sequence into Relational Database” (Figs 5 and 6), specifically "organizing the nucleotide sequences…into databases for rapid search and characterization of these sequences for functional and therapeutic relevance" ([0027]).
Regarding claim 2, Burgess teaches wherein is sonicated for 9x15 second pulses (i.e., less than 15 minutes) ([0102]).
Regarding claim 3, Burgess teaches wherein the chromatin is incubated after sonication in a buffer having a salt concentration of at least 150 mM ([0103]-[0105]).
Regarding claim 4, the recited catalog number in the instant claim merely identifies a commercial source of a rabbit monoclonal antibody for FoxO1, and does not impart structural or functional distinction beyond the antibody's known specificity and origin. Burgess teaches wherein the antibodies are of rabbit origin ([0040]), and either polyclonal or monoclonal origin to directly and specifically recognize, bind and extract a protein/DNA complex from a bulk population of cross-linked protein/DNA complexes ([0042]).
Regarding claims 7 and 8, Burgess teaches "cell lines from which transcription factor target genes may be discovered via methodologies provided by the presently described invention include…RD (human, Caucasian muscle, rhabdomyosarcoma…)" ([0062], pg. 8, right-column).
Regarding claim 9, Burgess teaches an actual reduction to practice of method using antibody that binds to p53, wherein the chromatin is obtained from Hela cells grown to 60% confluency on a 100 mm petri dish ([0102]), which is at least 1,000 cells as recited in the instant claim.
Regarding claim 10, Burgess teaches a step of cross-linking the chromatin before chromatin recovery (Fig 3 and 5, [0008-0010]).
Regarding claims 11 and 12, Burgess teaches using the ChIP method, followed by analysis of recovered DNA to identify target sequences for chosen transcription factor (see discussions applied to claim 1). Burgess further teaches the claimed invention "allows for discovery of target genes and their regulatory elements" ([0007]). The method taught by Burgess identifies gene-associated sequences, as proteins such as FOXO1 bind to gene regions including promoters, exons, introns, and other portions of a gene. Thus, the method of Burgess identifies at least 1,000 locations in the genome and wherein one or more of the genomic regions are a portion of a gene.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Burgess (US 2006/0292560 A1; Published Date: 28 Dec, 2006) as applied to claim 1 above, and further in view of Barr (Oncogene, 2001, 20, 5736-5746).
Regarding claim 5, the teachings of Burgess regarding the method of claim 1 and claim 8, wherein the cells used in the ChIP method is a rhabdomyosarcoma cell, is discussed above and applied to claims 1 and 8.
However, Burgess does not teach wherein the DNA Binding Domain is PAX3.
Barr teaches chromosomal translocations are characteristics of alveolar rhabdomyosarcoma, and these translocations rearrange PAX3 and juxtapose it with FKHR, generating PAX3-FKHR chimeric genes that are expressed as chimeric transcripts that encode chimeric proteins (Abstract).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Burgess’s method using rhabdomyosarcoma cancer cell with alveolar rhabdomyosarcoma cancer cells containing PAX3-FKHR chimeric proteins taught by Barr because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of characterizing unknown target sites of PAX3-FKHR chimeric proteins (i.e., FOXO1-DNA Binding Domain Fusion Protein). One would have had a reasonable expectation of success in doing so because Burgess already teaches a ChIP method using rhabdomyosarcoma cancer cells to study target sites of FOXO1.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Burgess (US 2006/0292560 A1; Published Date: 28 Dec, 2006) as applied to claim 1 above, and further in view of Schneider et al (Genome Res. 2017, 27(5):849–864).
Regarding claim 6, the teachings of Burgess regarding the method of claim 1 and wherein the cell is a human cell is discussed above and applied to claims 1 and 8. Burgess further teaches analyzing the characterizing the nucleotide sequences for functional relevance ([0027]) and utilizing computer programs such as BLAST, BLASTX, BLASTP, TBLASTN ([0098]), which are well-known tools for comparing sequence reads to reference genomic databases.
It is noted that the human genome UCSC hg38, also known as GRCh38, was released in 2013-2014, several years after the publication of Burgess. Therefore, Burgess does not explicitly or inherently disclose alignment with GRCh38.
Scheneider teaches GRCh38 "reflects the resolution of roughly 1000 tissues and encompasses modifications ranging from thousands of single base changes to megabase-scale path reorganizations, gap closures, and localization of previously orphaned sequences" (Abstract).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified the alignment strategy used in the method of Burgess with a current and updated human genome assembly taught by Scheneider because it would have merely amounted to applying a known technique to a known method ready for improvement to yield predictable results. One would have been motivated to have done so for the advantage of characterizing and mapping unknown target sites of transcription factors with improved accuracy. One would have had a reasonable expectation of success in doing so because Burgess and Scheneider both teach alignment of DNA sequences to the human genome.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Burgess (US 2006/0292560 A1; Published Date: 28 Dec, 2006) as applied to claim 1 above, and further in view of Dharaneeswaran et al (Circulation Research, 2014, 115(2): 238-251).
Regarding claim 13, the teachings of Burgess regarding the method of claim 1 and wherein the cell is a human cell is discussed above and applied to claims 1 and 8.
However, Burgess does not teach wherein the cells are rodent cells that express wild-type FOXO1.
Dharaneeswaran teaches mice and humans possess 4 FOXO members, including FOXO1, that "are highly related homologs with overlapping patterns of expression and transcriptional activities" (pg. 238, left-column).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified the human cells in Burgess’s method with rodent cells because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of studying FOXO1 binding sites in rodent cancer models. One would have had a reasonable expectation of success in doing so because Burgess already teaches the ChIP method can be used to discover transcription factors target site by using mouse cell lines, such as "13C4 (mouse/mouse, hybrid, hybridoma)" ([0062]).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIWEN SU-TOBON whose telephone number is (571)272-0331. The examiner can normally be reached Monday - Friday, 8:00am-4:30pm.
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QIWEN SU-TOBON
Examiner
Art Unit 1636
/NEIL P HAMMELL/ Supervisory Patent Examiner, Art Unit 1636