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 .
Application Status
This action is written in response to applicant’s correspondence received 09/05/2025. Claims 1, 5, 13, 17, 24, 29-31, 41, 43-44, 49-50,101, and 105-106 are currently pending. Claims 29-31, 44, 49-50,101, and 105-106 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1, 5, 13, 17, 24, 41, and 43 are examined herein.
Election/Restrictions
Applicant's election with traverse of Group I (claims 1, 5, 13, 17, 24, 29-31, 41, 43) in the reply filed on 09/05/2025 is acknowledged. The traversal is on the ground(s) that Groups I and II share the common structure of the elements of the APOB disrupting agent and that the alleged novel and nonobviousness of the site-specific APOB disrupting agent of Group I would necessarily uncover art relevant to the novelty and nonobviousness of the APOB disrupting agent of Group II and, therefore, function and should be examined together. This is not found persuasive because while Groups I and II are related products, the inventions as claimed have a materially different design, mode of operation, function, or effect because Group II requires a nucleic acid molecule encoding a fusion protein and an effector molecule, neither of which is required by Invention I. Furthermore, there would be a serious search and/or examination burden if restriction were not required at least because the inventions have acquired a separate status in the art in view of their different classification and the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries).
The requirement is still deemed proper and is therefore made FINAL.
Claims 29-31, 44, 49-50,101, and 105-106 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/05/2025.
Accordingly, claims 1, 5, 13, 17, 24, 41, and 43 are examined herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 17. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 17 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 17 references tables disclosed in the specification. MPEP 2173.05(s), states: “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).”
Therefore, claim 17 is indefinite because they are not complete in themselves. The information provided in the recited tables can be provided practically and concisely in the claims. Accordingly, the claims are indefinite.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 43 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 43 recites “A cell comprising the site-specific APOB disrupting agent of claim 1.” The specification states “The APOB gene may be in a cell, e.g., a mammalian cell, such as a mammalian somatic cell, e.g., a mouse or human somatic cell” (pp. 2 and 8). In addition, the specification states that the invention is intended to modulate the expression of an APOB gene for treating a subject who would benefit from modulating the expression of an APOB gene (page 2, paragraph 3). Accordingly, the broadest reasonable interpretation of the term “a cell” embraces a human host cell and wherein the host cell resides in a human organism and therefore is otherwise inseparable from the human. In view of BRI, a human comprising the host cell would be encompassed by the claimed product.
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.
Claims 1, 5, 13, 24, 41, and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McLaughlin (published 8/28/2014; see attached PTO-892).
Regarding claim 1, McLaughlin teaches a site-specific APOB disrupting agent comprising a site-specific moiety which targets an APOB expression control region (entire document; pp. 47-56).
Regarding claim 5, McLaughlin teaches the polymeric molecules of short hairpin polyamide and long linear sense polyamide site-specific APOB disrupting agents which target the APOB promoter region (pp. 26; and 47-56).
Regarding claim 13, McLaughlin teaches the APOB expression control region targeted by the site-specific APOB disrupting agent is the APOB promoter region (Fig. 3.1 and 3.11; and pp. 47-56).
Regarding claim 24, McLaughlin teaches that the polymeric molecules of short hairpin polyamide and long linear sense polyamide site-specific APOB disrupting agents are present in a composition with commercial transfection reagents (p. 33; and Fig. 3.7, 3.10, and 3.15).
Regarding claim 41, McLaughlin teaches vectors comprising nucleic acid molecules encoding the site-specific APOB disrupting agents (pp.30-33).
Regarding claim 43, McLaughlin teaches cells comprising the site-specific APOB disrupting agent (pp. 30-33; and Fig. 3.7, 3.10, and 3.15).
Therefore, McLaughlin anticipates claims 1, 5, 13, 24, 41, and 43.
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.
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 17 is rejected under 35 U.S.C. 103 as being unpatentable over McLaughlin (published 8/28/2014; see attached PTO-892), as applied to claims 1, 5, 13, 24, 41, and 43 above, and further in view of Zhang et al. (published 4/10/2019; see attached PTO-892).
The teachings of McLaughlin are discussed above and are applied to claim 17 as they are applied to claims 1, 5, 13, 24, 41, and 43 above.
However, McLaughlin does not specifically teach that the APOB targeting moiety comprises a polynucleotide encoding DNA-binding domains of zinc finger polypeptides or TALE polypeptides.
Zhang’s disclosure is directed to delivery of programmable site-specific nucleases to make precise and direct changes in the genomic DNA of various species, including human cells (see abstract and entire document).
Regarding claim 17, Zhang teaches using polynucleotides encoding DNA-binding domains of zinc finger nucleases and TALENs that specifically bind to target regions to disrupt expression (entire document). Zhang further teaches targeting APOB (p. 736, right column, para 1). Zhang teaches several delivery methods (Table 3). Zhang further teaches the electroporation of ZFN and TALEN mRNA in ex vivo and in vivo animal models (p. 740-741, right column, last para to left column, 3rd para).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified McLaughlin’s targeting of the APOB promoter with the techniques of Zhang using ZFN or TALENS. McLaughlin teaches targeting the APOB promoter region with shRNA and polyamides (see above). Zhang teaches disrupting the gene expression of APOB and further teaches using ZFN and TALENS to target specific sites through various delivery methods in vitro, ex vivo, and in vivo (see above). One would have recognized the versatility of using nucleases to disrupt gene expression of APOB. One would have had a reasonable expectation of success because both McLaughlin and Zhang teach disrupting APOB expression. Thus, the claimed invention as a whole is prima facie obvious.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636