DETAILED ACTION
Status of the Claims
Claims 1-5, 10, 13-14, 16, 19-20, 22, 25-26, 30-33, 45, 52, 56, and 58 are currently pending.
Claims 30-33, 45, 52, 56, and 58 have been withdrawn as being drawn to non-elected subject matter (see below).
Claims 1-5, 10, 13-14, 16, 19-20, 22, and 25-26 are examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Objection to the Abstract
Applicant is reminded of the proper language, content, and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as "means" and "said," should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. In certain patents, particularly those for compounds and compositions, wherein the process for making and/or the use thereof are not obvious, the abstract should set forth a process for making and/or use thereof. If the new technical disclosure involves modifications or alternatives, the abstract should mention by way of example the preferred modification or alternative.
The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
Where applicable, the abstract should include the following:
(1) if a machine or apparatus, its organization and operation;
(2) if an article, its method of making;
(3) if a chemical compound, its identity and use;
(4) if a mixture, its ingredients;
(5) if a process, the steps.
The abstract of the disclosure is objected to because it does not relate enough information about the disclosed invention(s) needed to "…disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details”, as per MPEP 608.01(b). Applicant is instructed to amend the abstract accordingly.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because several of the drawings (e.g., Fig. 6, 9, 11, 12, 21, 22, 24, 34, and others) contain text that is illegible. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Response to Restriction Requirement
Claims 30-33, 45, 52, 56, and 58 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/14/2026.
Applicant's election with traverse of Group I in the reply filed on 01/14/2026 is acknowledged. The traversal is on the ground(s) that the technical feature linking Groups I-IV and V is not a special technical feature and does not define a contribution over the prior art. This is not found persuasive because Bhatt discloses a transposase fused to a dCas9 domain, and the latter can reasonably be considered to label by its ability to bind to a target molecule.
The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claim 13 is objected to as being dependent upon a rejected base claim, but would be free from the prior art if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) – Indefiniteness
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 22 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 pre-AIA the applicant regards as the invention.
Claim 22 recites exemplary language including “such as”, “for example”, and “preferably”. As per MPEP § 2173.05(d):
Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made.
In each case of “such as”, “for example”, and “preferably” in the instant claims, it is unclear whether the claim is limited to the expressed examples/preferences, and therefore the metes and bounds of the claims are unascertainable.
Claim Rejections - 35 USC § 112(a) – Written Description
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 1-5, 10, 14, 16, 19-20, 22, and 25-26 are 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 claims contain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As per MPEP 2163(I), "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Also, as per MPEP 2163.03(V), there is a presumption that an adequate written description of the claimed invention is present in the specification as filed.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Possession may be shown in a variety of ways, for example, possession may be shown by describing an actual reduction to practice of the claimed invention. A specification may describe an actual reduction to practice by showing that the inventor constructed an embodiment or performed a process that met all the limitations of the claim and determined that the invention would work for its intended purpose. Cooper v. Goldfarb, 154 F.3d 1321, 1327, 47 USPQ2d 1896, 1901 (Fed. Cir. 1998). See also UMC Elecs. Co. v. United States, 816 F.2d 647, 652, 2 USPQ2d 1465, 1468 (Fed. Cir. 1987) ("[T]here cannot be a reduction to practice of the invention ... without a physical embodiment which includes all limitations of the claim."); Estee Lauder Inc. v. L’Oreal, S.A., 129 F.3d 588, 593, 44 USPQ2d 1610, 1614 (Fed. Cir. 1997) ("[A] reduction to practice does not occur until the inventor has determined that the invention will work for its intended purpose."); Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1578, 38 USPQ2d 1288, 1291 (Fed. Cir. 1996) (determining that the invention will work for its intended purpose may require testing depending on the character of the invention and the problem it solves). Alternatively, applicant may present that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it").
Finally, MPEP 2163.04 describes the burden on the examiner with regard to the Written Description requirement, stating that in rejecting a claim, the examiner must set forth express findings of fact which support the lack of written description conclusion. These findings should:
(A) Identify the claim limitation(s) at issue; and
(B) Establish a prima facie case by providing reasons why a person skilled in the art at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed in view of the disclosure of the application as filed.
Specifically, the claim limitation at issue is the breadth of embodiments encompassing the components of the fusion protein of claims 1-5, 10, 14, 16, 19-20, 22, and 25-26.
Claim 1 generally recites a method for analyzing open chromatin, the method comprising fragmenting and tagging accessible genomic DNA of the open chromatin, and labeling molecules proximal to the accessible genomic DNA. The broadest reasonable interpretation of this claim includes not only the use of a fusion protein, as detailed below, but also the use of two (or more) separate enzymes to perform the fragmenting and tagging of the genomic DNA and the labeling or proximal molecules.
Claim 2 recites “a fusion protein comprising (a) a first enzyme that fragments and tags the accessible genomic DNA of the open chromatin, and (b) a second enzyme that labels molecules proximal to the accessible genomic DNA”. Both the first and the second enzymes that form the fusion protein are defined by functional limitations. As per MPEP § 2173.05(g), a “claim term is functional when it recites a feature ‘by what it does rather than by what it is’”. The same MPEP section states that “[t]here is nothing inherently wrong with defining some part of an invention in functional terms” and that “[a] functional limitation must be evaluated and considered, just like any other limitation of the claim, for what it fairly conveys to a person of ordinary skill in the pertinent art in the context in which it is used.”
The broadest reasonable interpretation of the claimed fusion protein of claim 2 encompasses proteins or polypeptides whose sequence includes sequences from two or more proteins that do not naturally occur together within the same molecule (e.g., as per para [0081] of the published specification), namely, a first enzyme that fragments and tags accessible genomic DNA of open chromatin, and a second enzyme that labels molecules proximal to the accessible genomic DNA. Since these enzymes are claimed by their function, they reasonably encompass any enzymes that can perform the recited functions. For the first enzyme, which can fragment and tags accessible genomic DNA at open chromatin, this reasonably includes enzymes which can cleave and tag DNA, such as transposases, nucleases, integrases, restriction enzymes (e.g., as per para [0130] of the specification). The specification at para [0131] states “[i]n addition to the above-noted enzymes, fragments, analogs, and variants of the enzymes, and other enzymes having the requisite activity (i.e., fragmenting and tagging of DNA), can be used in the invention, provided that they maintain sufficient activity (i.e., fragmenting and tagging of DNA)”.
For the second enzyme, which can label molecules proximal to the accessible genomic DNA, this reasonably includes enzymes such as oxidases and peroxidases, ligases, kinases, transferases, polymerases, transglutaminases, and any enzyme able to otherwise label a molecule. The specification gives several specific examples and that “[i]n addition to the above-noted enzymes, fragments, analogs, and variants of the enzymes, and other enzymes having the requisite activity (i.e., proximity labeling of molecules such as proteins, peptides, RNA, and/or carbohydrates), can be used in the invention, provided that they maintain sufficient activity” (e.g., as per para [0136]).
Claim 5 slightly limits the genus of the first enzyme, claiming that “the first enzyme is selected from the group consisting of a transposase, a retroviral integrase, a DNA-binding enzyme, or a variant thereof”. Similarly, claim 10 limits the second enzyme, stating that “the second enzyme is selected from the group consisting of a peroxidase, a biotin ligase, a catalase-peroxidase, and an oxidase”. Claim 16 limits the enzymes by claiming that “the first enzyme tags genomic DNA fragments generated by the first enzyme with sequencing adaptors, and/or the second enzyme labels molecules proximal to the accessible genomic DNA with biotin”. Claims 4-5, 14, 19-20, 22, and 25-26 do not further limit the scope of the fusion protein components.
The disclosure as originally filed shows a clear reduction to practice of the invention (e.g., as per the Examples and Figures) for fusion proteins comprising several permutations of Tn5 and APEX2 combinations with various linkers and/or tags. Therefore, it is apparent that Applicant was in possession of combinations of Tn5 and APEX2 as of the effective filing date.
However, as detailed in MPEP § 2163, besides an actual reduction to practice, Applicant may prove possession of the claimed invention by a showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention. Further, as per MPEP § 2163, “[f]or some arts, there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement.”
In the present case, the specification does little more than list some alternatives for the first and second enzymes. However, it is noted, as per the review by Cain et al. (Nature Reviews Genetics, 2020, 21:526-540) that around the time of the effective filing date, it was well known to utilize several different transposases in fragmenting and tagging genomic DNA. Similarly, in the area of proximity labeling, Gentzel et al. (Methods, 2019, 164-165, pp. 67-72) discloses that BirA and various ascorbate peroxidases were well known for such purposes. However, there is no indication that Applicant was in possession of fusion proteins that utilized a first enzyme other than a transposase, and a second enzyme other than BirA (or variant thereof) or one of several known ascorbate or horseradish peroxidases.
Claim Rejections – 35 U.S.C. 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 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.
Stanford
Claims 1, 3, and 22 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Stanford (WO 2019/152108 A1, cited in IDS of 06/14/2022).
Regarding claim 1, Stanford discloses a method for analyzing open chromatin, the method comprising fragmenting and tagging accessible genomic DNA of the open chromatin (e.g., using Tn5 as per para [0367]), and labeling molecules proximal to the accessible genomic DNA (e.g., on the gRNAs as per para [0367]).
Regarding claim 3, Stanford discloses the above method, wherein the molecules proximal to the accessible genomic DNA are proteins, peptides, or RNA molecules (e.g., on the gRNAs as per para [0367]).
Regarding claim 22, Stanford discloses the above method, wherein the open chromatin is obtained from cells of a subject, such as cells within a tissue biopsy or a blood sample, or from cultured cells (e.g., as per para [0198]).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEREMY FLINDERS whose telephone number is (571)270-1022. The examiner can normally be reached M-F 10-6:00 EST.
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/JEREMY C FLINDERS/
Primary Examiner, Art Unit 1684
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