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 .
DETAILED ACTION
Application status
In response to the previous Office action, a non-final rejection (mailed on 11/17/2025), Applicants filed a response and amendment received on 02/17/2026. Said amendment canceled Claims 1-26, 47-48, 50 and 52-60, and amended claim 27, 49 and 51. Thus, Claims 27-46, 49 and 51 are at issue and present for examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/17/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 U.S.C. § 112 – WITHDRAWN
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 previous rejection of Claims 51-60 under 35 U.S.C. 112(b) 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn because Applicants have canceled these claims.
The Examiner notes that Applicants’ arguments regarding the previous rejections are moot since these rejections are withdrawn.
Claim Rejections - 35 U.S.C. § 112(b) – A NEW REJECTION necessitated by Applicants’ amendment to claims
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.
Claims 27-46, 49 and 51 are rejected under 35 U.S.C. 112(b) 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 27 (claims 28-46, 49 and 51 dependent therefrom) recite “a first monomer and a second monomer, wherein: the first monomer comprises the amino acid sequence of a recombinase selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto, or an amino acid sequence having at least 90% sequence identity thereto; the second monomer comprises the amino acid sequence of a recombinase selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto, or an amino acid sequence having at least 90% sequence identity thereto” is unclear and indefinite (italicized for added emphasis). Due to the naturally occurring genetic polymorphisms which may be present for each of these recombinases, it is unclear what the exact amino acid sequences are for each of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto recombinases. Furthermore, without the exact amino acid sequences of each of these Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto recombinases, it is unclear how one can determine “an amino acid sequence having at least 90% sequence identity thereto” is. Similarly, it is unclear how one can determine “the first monomer and the second monomer differ in at least 2% of their amino acid residue” when one cannot determine what the exact amino acid sequences of these recombinases are. Therefore, it is unclear what the metes and bounds of the exact amino acid sequences are for each of the recited recombinases. The Examiner suggests inserting a SEQ ID NO corresponding to each of these recombinases, i.e., Cre comprising the amino acid sequence as set forth in SEQ ID NO: 1, in order to overcome the instant rejection.
In the interest of advancing prosecution, claim 27 is interpreted as “A method for site-specific DNA recombination, comprising introducing into a host cell a DNA-recombining enzyme, wherein the DNA-recombining enzyme comprises a first monomer and a second monomer, wherein: the first monomer is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto; the second monomer is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto; and the first and the second monomer each recognize non-identical naturally occurring half sites in a genome of a host cell.”
Claim 51 recites that “The method of claim 27, wherein the amino acid sequence of the first monomer and the amino acid sequence of the second monomer share a sequence identity of between 70% to 98%” which is unclear and indefinite (italicized for added emphasis). It is unclear how one can determine how much of percent sequence identity two different monomers share without knowing what the exact sequence for these two different monomers are (similar to what is noted above for claim 27).
In the interest of advancing prosecution, claim 51 is interpreted as “The method of claim 27, wherein the amino acid sequence of the first monomer and the amino acid sequence of the second monomer are not identical.”
Claim Rejections - 35 U.S.C. § 112 – MAINTAINED
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.
Claims 27-46, 49 and 51 are rejected under 35 U.S.C. § 112(a), written description, as failing to comply with the written description requirement. The claim(s) contains 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(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a method for site-specific DNA recombination, comprising introducing into a host cell a DNA-recombining enzyme, wherein the DNA-recombining enzyme comprises a first monomer and a second monomer, wherein: the first monomer is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto; the second monomer is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto; and the first and the second monomer each recognize non-identical naturally occurring half sites in a genome of a host cell (see above 112(b) rejection for the claim interpretation).
To satisfy the written description aspect of 35 U.S.C. § 112(a) for a claimed genus of methods, it must be clear that: (1) the identifying characteristics of the claimed methods have been disclosed, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these; and (2) a representative number of species within the genus must be disclosed.
University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lily and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description as noted from Enzo Biochemical (see above).
The specification discloses only a single representative species of a method for site-specific DNA recombination, comprising introducing into a host cell a DNA recombining enzyme having the amino acid sequence as set forth in SEQ ID NO: 1 (Rec F9-1) and SEQ ID NO: 2 (Rec F9-2) (see pages 46-47), which recognize recombination target sites as set forth in SEQ ID NO: 7 (loxF9a) and SEQ ID NO: 8 (loxF9b) (see page 49). However, this single disclosed species fails to provide adequate written description for a genus of claimed methods which encompass a method for site-specific DNA recombination, comprising introducing into a host cell a DNA-recombining enzyme, wherein the DNA-recombining enzyme comprises a first monomer and a second monomer, wherein: the first monomer is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto; the second monomer is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto; and the first and the second monomer each recognize non-identical naturally occurring half sites in a genome of a host cell (italicized for added emphasis).
In this case, the specification fails to describe any identification of structural characteristics or properties of [1] a genus of any first monomer which is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto, and a genus of second monomer which is selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto, wherein the first and the second monomer differ in at least 2% to as much as 100% of their amino acid residues; and [2] a genus of any non-identical naturally occurring half sites in a genome of a host cell having any sequence; and how such structural characteristics or properties of the first and the second monomer of a recombinase affect the desired function of recognizing any non-identical naturally occurring half sites (italicized for added emphasis). The Examiner notes that a genus of 1st and 2nd monomers which are selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto, and differ in at least 2% to as much as 100% of their amino acid residues encompasses use of wide variant recombinase monomers having any structural or functional similarity.
In other words, the genus of claimed methods encompasses the use of DNA-recombining enzymes comprising widely variant species of recombinase comprising structurally different 1st and 2nd monomers; and the use of a genus of any non-identical naturally occurring half sites in a genome of a host cell having any sequence. However, with the limited disclosure of a single example as shown in the specification, Applicants have failed to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted by the Examiner that none of the dependent claims remedy the deficiencies noted above regarding the “written description” requirement.
While M.P.E.P. section 2163 acknowledges that a single species can describe a genus, it also acknowledges that for a genus that encompasses widely variant species, disclosure of a single species within the genus fails to adequately describe all members of the genus. Please refer to the M.P.E.P. section 2163.05 [R-7.2022] under I, B for more details with respect to sufficient number of representative species that should be disclosed to describe a widely variant genus.
Given the lack of additional representative species of the genus of “DNA-recombining enzymes” and the genus of “non-identical naturally occurring half sites” having essentially any structure as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
It is noted by the Examiner that all of the dependent claims are included in this rejection because none of them remedy the deficiency with regard to the ‘written description’ requirement as discussed above.
Applicants’ Arguments:
As amended, claim 27, from which all other claims depend, is directed to a DNA- recombining enzyme that comprises a first monomer and a second monomer, and specifies that the first monomer and the second monomer comprise the amino acid sequence of a recombinase selected from the group consisting of Cre, Dre, VCre, sCre, FLP, Tre, Vika, Nigri, and Panto, or an amino acid sequencer having at least 90% sequence identity thereto. As such, the sequences of the monomers are specifically defined in the claims, and the claims relate to a finite number of recombinases. Applicant notes that the amino acid sequences of the recited recombinases are known and readily available in the art. For example, such sequences are referred to in the present application at paragraphs [0006] and [0007] of the published specification.
Examiner’s Explanation:
Applicants’ arguments have been fully considered but are not deemed persuasive for the following reasons. Contrary to Applicants’ arguments, the Examiner notes that there are no sequences of recombinase monomers disclosed in para [0006] and [0007]. Furthermore, due to the recitation “wherein the first and the second monomer differ in at least 2% of their amino acid residues” which encompasses those monomers that are differ by as much as 100% of their amino acid residues because there is no recitation of an upper limit, this opens the genus of designer DNA-recombining enzymes to encompass widely variant species of recombinase monomers, having essentially any structure. As such, the invention as claimed continues to remedy the deficiencies noted above regarding the “written description” requirement.
Claim Rejections - 35 USC § 102 – WITHDRAWN
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.
The previous rejection of Claims 27-46, 49 and 51-60 under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Havranek et al. (US Patent 10017832 with earlier filing date of 08/25/2015) is withdrawn because Havranek et al. do not teach the use of non-identical naturally occurring half sites (they used engineered lox sites).
Conclusion
Claims 27-46, 49 and 51 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
THIS ACTION IS MADE FINAL. 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (5712720939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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