DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
A Preliminary Amendment was filed on July 5, 2022, in which claims 1-19, 33, 35, 37, 40-54, and 57-70 were canceled. Claims 20-32, 34, 36, 38-39, and 55-56 are pending in this application, and are under examination.
Information Disclosure Statement
The Information Disclosure Statements filed July 5, 2022 (2) have been considered.
Specification
The specification is objected to because the use of the trademarks PCDNA™5/FRT at page 40, line 20; LIPOFECTAMINE® at page 41, line 2; CELL LAB QUANTA™ at page 41, line 6; RIBOMAX™ at page 41, line 26 and page 46, line 10; NUCLEOFECTOR™ at page 43, line 4 and page 46, line 18; FLEXIGENE® at page 43, line 6 and page 46, line 20; and ZEOCIN™ at page 43, lines 19, 23, and 26; has been noted in this application. They should be capitalized wherever they appear and be accompanied by the generic terminology.
Although the use of trademarks is 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 trademarks.
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 22, 31-32, 34, 36, and 38-39 are 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.
At claim 22, line 2, the phrase “gene of interest” is indefinite because a gene that is of interest to one practitioner might, or might not, be of interest to a different practitioner. Because the phrase “gene of interest” is subjective, the metes and bounds of the claim are unclear.
At claim 31, lines 21, 25, 28, and 30, the phrase “sequence of interest” is indefinite because a sequence that is of interest to one practitioner might, or might not, be of interest to a different practitioner. Because the phrase “sequence of interest” is subjective, the metes and bounds of the claim are unclear.
Claims 32, 34, 36, and 38-39 depend from claim 31, and are therefore included in this rejection.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 20-23, 25, and 27-32, 34, 36, and 38-39 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Gaucher et al. (Canadian Patent Application Publication No. 2 671 825, published August 14, 2008, and cited in the Information Disclosure Statement filed March 1, 2018).
Regarding claims 20, Gaucher discloses a method of inserting an exogenous sequence into an amplifiable locus of a mammalian cell comprising providing a mammalian cell that has an endogenous target site, where the target site comprises a recognition sequence for an engineered meganuclease, a 5' flanking region, and a 3' flanking region; introducing a double-stranded break between the flanking regions; contacting the cell with a donor vector that comprises a donor 5’ flanking region that is homologous to the endogenous 5’ flanking region; an exogenous sequence; and a donor 3’ flanking region that is homologous to the endogenous 3’ flanking region (page 3, line 29 to page 4, line 7 and page 23, line 33 to page 26, line 3). Gaucher discloses that the selectable gene permits amplification of selectable gene (page 23, line 33 to page 26, line 3). Gaucher discloses that the donor flanking regions and the exogenous sequence are inserted into the cell by homologous recombination (page 23, line 33 to page 26, line 3).
Regarding claims 21, Gaucher discloses that the endogenous target site is proximal to a selectable gene (page 23, line 33 to page 26, line 3). Gaucher discloses that the selectable gene may be dihydrofolate reductase (DHFR) or glutamine synthetase (GS) (page 30, lines 2-18). Gaucher further discloses that the locus can be methotrexate or methionine sulfoximine, when the selectable gene is DHFR or GS, respectively (page 30, lines 2-18).
Regarding claim 22, Gaucher discloses that the exogenous sequence can encode a gene of interest (page 14, lines 12 to page 17, line 3).
Regarding claims 23 and 25, Gaucher discloses that the target site can be either downstream from the 3' regulatory region of the selectable gene or upstream from the 5' regulatory region of the selectable gene (page 23, line 33 to page 26, line 3).
Regarding claims 27-30, Gaucher discloses that the selectable gene may be dihydrofolate reductase (DHFR) or glutamine synthetase (GS) (page 30, lines 2-18). Gaucher further discloses that the locus can be methotrexate or methionine sulfoximine, when the selectable gene is DHFR or GS, respectively (page 30, lines 2-18).
Regarding claim 31, Gaucher discloses a second step for inserting a DNA molecule of interest in the cell line generated by the method of inserting an exogenous sequence into an amplifiable locus of a mammalian cell, with the DNA molecule of interest being expressible in the engineered cell. (page 37, line 15 to page 39, line 26). Gaucher discloses that the exogenous sequence can encode a gene of interest (page 14, lines 12 to page 17, line 3).
Regarding claim 32, Gaucher discloses that the endogenous target site is proximal to a selectable gene (page 23, line 33 to page 26, line 3). Gaucher discloses that the selectable gene may be dihydrofolate reductase (DHFR) or glutamine synthetase (GS) (page 30, lines 2-18). Gaucher further discloses that the locus can be methotrexate or methionine sulfoximine, when the selectable gene is DHFR or GS, respectively (page 30, lines 2-18).
Regarding claims 34 and 36, Gaucher discloses that the target site can be either downstream from the 3' regulatory region of the selectable gene or upstream from the 5' regulatory region of the selectable gene (page 23, line 33 to page 26, line 3).
Regarding claims 38-39, Gaucher discloses that the selectable gene may be dihydrofolate reductase (DHFR) or glutamine synthetase (GS) (page 30, lines 2-18). Gaucher further discloses that the locus can be methotrexate or methionine sulfoximine, when the selectable gene is DHFR or GS, respectively (page 30, lines 2-18).
Gaucher discloses each and every limitation of claims 20-32, 34, 36, and 38-39, and therefore anticipates claims 20-32, 34, 36, and 38-39.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 24 and 26 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gaucher et al. (Canadian Patent Application Publication No. 2 671 825, published August 14, 2008, and cited in the Information Disclosure Statement filed March 1, 2018).
Gaucher discloses a method of inserting an exogenous sequence into an amplifiable locus of a mammalian cell, as discussed above.
Gaucher fails to explicitly disclose or suggest the distance of the endogenous target site from either the 3’ or the 5' regulatory region of the selectable gene.
However, regarding claims 24 and 25, it would have been obvious to one with ordinary skill in the art at the time the invention was made to engineer a target site that is from 0 to 100,000 base pairs downstream from the 3' regulatory region of the selectable gene or upstream from the 5' regulatory region of the selectable gene because determining the optimum or workable ranges of the distance of the target site from the selectable gene is routine in the art. One of ordinary skill in the art would be motivated to determine the optimal distance in order to maintain selection of the cells carrying a copy of the target vector.
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 20-32, 34, 36, 38-39, and 55-56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9,822,381.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘381 patent and the instant application claim a method for inserting an exogenous sequence into an amplifiable locus of a mammalian cell via homologous recombination, after introducing a double strand break in an endogenous target site. The claims of the ‘381 patent differ from the instant claims in that the engineered meganuclease of the ‘381 patent has a sequence with at least 90% identity to SEQ ID NO: 9 and cleaves a recognition site having SEQ ID NO: 7.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘381 patent claims a method for inserting an exogenous sequence into an amplifiable locus of a mammalian cell via homologous recombination, after introducing a double strand break in an endogenous target site using an engineered meganuclease that has a sequence with at least 90% identity to SEQ ID NO: 9 and cleaves a recognition site having SEQ ID NO: 7. The patented method requires the provision of the instantly claimed meganuclease (SEQ ID NO: 9) and meganuclease cleavage site (SEQ ID NO: 7).
Further, it would have been obvious to one with ordinary skill in the art at the time the invention was made to add additional steps of introducing a second double-stranded break between the 5’ and 3’ flanking regions of the target site, contacting cell with a sequence of interest donor vector, where homologous recombination takes place, providing an engineered mammalian cell having the sequence of interest because this provide a mechanism to introduce a desired sequence for expression in an engineered cell.
Therefore, the instant claims are not patentably distinct from the claims of the reference application.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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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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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636