DETAILED ACTION
Status of the Claims
Claims 2-5, 10, 13-14, 19-20, 22, 25-26, and 67-72 are currently pending and are examined herein.
The following Office Action is in response to Applicant’s communication dated 09/08/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Withdrawn Objection(s) and/or Rejection(s)
The objection to the Abstract and to the Drawings are withdrawn in light of Applicant’s submission of a replacement Abstract and Drawings in the 09/08/2026 response.
The rejection of claim 22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of amendments made to the claim by Applicant in the 09/08/2026 response.
The rejection of claims 1, 3, and 22 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35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Stanford (WO 2019/152108 A1, cited in IDS of 06/14/2022) is withdrawn in light of amendments made to the claim by Applicant in the 09/08/2026 response.
Modified/New Claim Objection(s)
Necessitated by Amendments
Claims 10, 13, 67-68, and 70-71 are 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.
Modified Claim Rejections - 35 USC § 112(a) – Written Description
Necessitated by Amendments
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 2-5, 14, 19-20, 22, 25-26, 69, and 72 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 2-5, 14, 19-20, 22, 25-26, 69, and 72.
Claim 2 generally recites a method for analyzing open chromatin using a fusion protein comprising (1) a transposase, a retroviral integrase, a DNA-binding enzyme, or a variant thereof; and (2) a peroxidase, a biotin ligase, a catalase-peroxidase, an oxidase, or a variant thereof. Regarding what is encompassed by the term “variants”, paragraph [0131] of the published application states:
[0131] In 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). Thus, for example, enzyme variants that maintain fragmenting and tagging activity, and have at least about 70%, 75%, 80%, 85%, 90%, 92%, 94%, 95%, 97%, 98%, or 99% amino acid sequence identity to a transposase, integrase, or other DNA-binding enzyme, e.g., an exemplary first enzyme listed above, or a fragment thereof (e.g., a fragment of at least about 15, 20, 30, 40, 50, 60, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, or 600 amino acids in length), can be used. Also included are variants having one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more amino acid substitutions or deletions, provided that they maintain sufficient activity. Moreover, the variant sequences can be present in the enzymes or in tag and/or linker sequences, as described herein.
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.
Regarding the first enzyme, the scope of claim 2 encompasses embodiments wherein the enzyme in a transposase, a retroviral integrase, a DNA-binding enzyme, or a variant thereof. Aside from the Tn5 transposase, no other first enzymes were reduced to practice. For the genus of transposases, while no other examples were reduced to practice, it is noted that as per the review by Cain et al. (Nature Reviews Genetics, 2020, 21:526-540, of record) that around the time of the effective filing date, it was well known to utilize several different transposases in fragmenting and tagging genomic DNA. Therefore, the disclosure as originally filed appears to have sufficient written description support for transposases for the first enzyme.
Regarding retroviral integrases, the disclosure does not provide any reduction to practice, nor does it describe in sufficient detail any distinguishing identifying characteristics sufficient to show that the Applicant was in possession of such an enzyme for genomic DNA fragmenting and tagging. 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.” While it was well known that retroviral integrases possess DNA endonuclease and strand transfer activity, the present disclosure does not describe in sufficient detail how this is to be used in the genomic DNA fragmenting and tagging as recited in claim 2, for example, how it may be used to cleave the open chromatin or any indication of what the integrase may use to tag the DNA. For the genus of DNA-binding enzymes as per claim 2, the specification (and claim 69) recite that this may include DNase, MNase, and restriction enzymes. While these are well known to cleave or fragment genomic DNA, no indication is provided on the manner of subsequent tagging. Furthermore, these enzymes are not generally known to possess any tagging functionality whatever. Therefore, it must be concluded that Applicant was not in possession of retroviral integrases or DNA-binding enzymes for the first enzyme of the fusion protein of the claims.
For the second enzyme of the claimed fusion protein, the disclosure (as above) details a reduction to practice for APEX2, a well-known peroxidase useful for proximity labeling. However, in the area of proximity labeling, much more was generally known in the art for their routine use, for example, Gentzel et al. (Methods, 2019, 164-165, pp. 67-72, of record) discloses that BirA and various ascorbate peroxidases were well known for such purposes. Therefore, even in the absence of an actual reduction to practice or extensive descriptions of identifying characteristics, such proximity labeling was well enough established to reasonably conclude that Applicant was in possession of the peroxidases and biotin ligases as claimed, for example, in claims 10-11 and 70-71.
(Note that the result of this analysis shows that claims 10, 13, 67-68, and 70-71 have sufficient written description support in the disclosure as originally filed and are not rejected here.)
***
Response to Arguments
The 09/08/2026 remarks argue: claims satisfy the written description requirement.
RE: “As to the description of the fusion protein, the Applicant submits that the first and second enzyme genera were known in the art as of the filing date, as acknowledged by the Office (Office Action, page 10), and reflected by the routine use of these enzymes. Given that these classes of enzymes were known as of the filing date, the Applicant need not re-describe the enzymes in order to satisfy the written description requirement.”
Applicant's arguments have been fully considered but they are not persuasive for at least the following reasons.
While it is true that the members of the first and second enzyme genera were well known in the art, it is respectfully noted that the claims are not merely drawn to these enzymes by themselves, but instead are drawn to fusion proteins comprised of these enzymes (and linkers and tags) and to their specific use in analyzing open chromatin by the combined functions of fragmenting and tagging accessible genomic DNA and labeling of biomolecule proximal to the accessible genomic DNA. In fact, the careful and deliberate experimentation and optimization performed by Applicant in the specification for the specific combination of Tn5 and APEX2 (e.g., as detailed in Fig. 2 and Example 1) supports the assertion that performing the claimed invention was much more than simply selecting known classes of enzymes and fusing them together. The demanding nature of the claimed methods and the unpredictability of enzyme fusions dictates the level of detail required by the written description requirement sufficient to show possession.
New Claim Rejections - 35 USC § 112(b) – Indefiniteness
Necessitated by Amendments
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 69 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 69 recites that the first enzyme that fragments and tags the accessible genomic DNA of the open chromatin is a “DNA-binding enzyme is selected from the group consisting of a DNase, an MNase, a restriction enzyme, and variants thereof”, however, it is noted that while DNases, MNases, and restriction enzymes generally may cleave/fragment DNA, they do not reasonably “tag” DNA as the term is used in the disclosure as originally filed (e.g., as per para 0156). Therefore, the metes and bounds of the claim are unascertainable.
As per MPEP 2173: It is of utmost importance that patents issue with definite claims that clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter. Therefore, claims that do not meet this standard must be rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph as indefinite. Further, as per MPEP 2173.02: If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. As currently written, the metes and bounds of the rejected claims are unascertainable for the reasons set forth above, thus the above claim(s) and all dependent claims are rejected under 35 USC 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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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