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 .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Status
Claims 1-19 are pending and under review with an effective filing date of October 27, 2022.
Claim Rejections - 35 USC § 112(b)
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 1-19 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.
Claims 1, 12 and 13 recite the limitation "the stop sequence" in lines 12 and 21 of Claim 1, lines 9 and 12 in Claim 12 and lines 12 of Claim 13. There is insufficient antecedent basis for this limitation in each claim. Applicant may amend the first instance of “the stop sequence” to “a stop sequence” in each claim to overcome this rejection.
Regarding Claims 1, 12 and 13, Claims 1, 12 and 13 recite “CRE/Lox inversion of the transposase to forward orientation”. Transposase is a protein, while the CRE/Lox inversion occurs on a nucleotide sequence. It is not clear if this should be read as “transposase sequence” or the protein itself is being inverted by CRE/Lox.
Claims 2-11, dependent on Claim 1, and Claims 14-19, dependent on Claim 13, are rejected for depending from the rejected claims above but fail to remedy the indefiniteness therein.
Claim 2 contains the trademark/trade name “Sleeping Beauty”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to describe a transposase and, accordingly, the description is indefinite.
Regarding Claims 8 and 19, Claims 8 and 19 incorporate Table 3. 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’”. To overcome this rejection, applicant may list the appropriate sequences or structures to be claimed within the claim itself.
Regarding Claim 10, the phrase "(e.g., ...) " renders the claim indefinite because it is unclear whether the limitation following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 1-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ngo, K. et. al., WO 2021/146666 A2, published July 22, 2021.
Regarding Claim 1, Ngo teaches in Claim 1 of Ngo, “A system for conditional control of gene copy number amplification in an expression host cell, the system comprising: 1) a nucleic acid master regulatory construct comprising: a transposase sequence in reverse orientation downstream from a promoter sequence, which promoter sequence is controlled by an inducing agent; a Cre recombinase sequence with expression controlled by the inducing agent; and, wherein the transposase sequence is upstream from a reverse oriented heterotypic first Lox sequence and downstream from a second Lox sequence, which second lox sequence is forward oriented between the promoter sequence and the transposase sequence; and, wherein the stop sequence is bracketed by a pair of forward oriented lox sequences; 2) an expression transposon nucleic acid construct comprising: a transposon sequence encoding a protein sequence of interest flanked by inverted terminal repeats (ITRs), which ITRs are the binding target of the transposase; and, a binding site (BS) for the first transcriptional activator upstream from the ITRs; wherein the presence of the inducing agent induces expression of Cre, resulting in CRE/Lox inversion of the transposase to forward orientation and resulting in excision of the stop sequence, thus resulting in expression of the transposase; enabling insertion of the transposon at particular sate harbor loci (SHL) of interest for expression of the protein of interest.” (p. 69), which is Claim 1 of the instant application. Therefore, Claim 1 is anticipated by Ngo.
Regarding Claim 2, Ngo teaches in Claim 2 of Ngo, “The system of claim 1, wherein the transposase is a Sleeping Beauty transposase” (p. 69) , which is Claim 2 of the instant application. Therefore, Claim 2 is anticipated by Ngo.
Regarding Claim 3, Ngo teaches in Claim 3 of Ngo, “The system of claim 1, further comprising one or more second transcriptional activators in the form of a ligand/receptor inducing agent” (p. 69), which is Claim 3 of the instant application. Therefore, Claim 3 is anticipated by Ngo.
Regarding Claim 4, Ngo teaches in Claim 4 of Ngo, “The system of claim 3, wherein one or more of the master regulatory control construct promoter sequences is a TRE3G promoter and the inducing agent is doxycycline/reversible tetracycline transcriptional activator (Dox/rtTA)” (p. 69), which is Claim 4 of the instant application. Therefore, Claim 4 is anticipated by Ngo.
Regarding Claim 5, Ngo teaches in Claim 5 of Ngo “The system of claim 1, wherein the protein of interest is an antibody heavy chain or an antibody light chain”(p. 70), which is Claim 5 of the instant application. Therefore, Claim 5 is anticipated by Ngo.
Regarding Claim 6, Ngo teaches in Claim 6 of Ngo “The system of claim 1, wherein the host cell is selected from the group consisting of: SP2/0, NS0, HEK293T, Vero, and CHO” (p. 70), which is Claim 6 of the instant application. Therefore, Claim 6 is anticipated by Ngo.
Regarding Claim 7, Ngo teaches in Claim 7 of Ngo “The system of claim 1, wherein insertion of the transposon is enabled by knock-in into one or more Safe Harbor Loci (SHL) by AAV and CRISPR enzymes Cas9, Cas12a (Cpfl), Cas12b, CasX, or CasY” (p. 70) which is Claim 7 of the instant application. Therefore, Claim 7 is anticipated by Ngo.
Regarding Claim 8, Ngo teaches in Claim 8 of Ngo “The system of claim 7, wherein the SHL is selected from the SHLs of Table 3” (p. 70), which is Claim 8 of the instant application. Table 3 is on pages 28-30 of the instant application is identical to Table 3 on pages 28-30 of Ngo. Therefore, Claim 8 is anticipated by Ngo.
Regarding Claim 9, Ngo teaches in Claim 9 of Ngo “The system of claim 1, wherein the master regulatory construct and expression transposon construct are on the same nucleic acid” (p. 70), which is Claim 9 of the instant application. Therefore, Claim 9 is anticipated by Ngo.
Regarding Claim 10, Ngo teaches in Claim 10 of Ngo “The system of claim 1, wherein the master regulatory construct further comprises a ubiquitous promoter controlling expression of the reversible tetracycline transcriptional activator (rtTA) and a selective pressure resistance factor (e.g., Bsd)” (p. 70), which is Claim 10 of the instant application. Therefore, Claim 10 is anticipated by Ngo.
Regarding Claim 11, Ngo teaches in Claim 11 of Ngo “The system of claim 10, wherein the ubiquitous promoter is selected from the group consisting of: EF1a, CAG, Cbh, SV40, UBC, CMV, EFS, and CMV promoter combined with CMV immediate early enhancer elements” (p. 70), which is Claim 11 of the instant application. Therefore, Claim 11 is anticipated by Ngo.
Regarding Claim 12, Ngo teaches in Claim 12 of Ngo “A nucleic acid master regulatory construct comprising: a transposase sequence in reverse orientation downstream from a promoter sequence, which promoter sequence is controlled by an inducing agent; a Cre recombinase sequence with expression controlled by the inducing agent; wherein the transposase sequence is upstream from a reverse oriented first heterotypic Lox sequence and downstream from a second Lox sequence, which second Lox sequence is forward oriented between the promoter sequence and the transposase sequence; and, wherein the stop sequence is bracketed by a pair of forward oriented lox sequences whereby the presence of the inducing agent induces expression of Cre, resulting in CRE/Lox inversion of the transposase to forward orientation and resulting in excision of the stop sequence, thus resulting in expression of the transposase” (p. 70), which is Claim 12 of the instant application. Therefore, Claim 12 is anticipated by Ngo.
Regarding Claim 13, Ngo teaches in Claim 13 of Ngo “A method for conditional control of gene copy number amplification in an expression host cell, the method comprising: 1) providing a nucleic acid master regulatory construct comprising: a transposase sequence in reverse orientation downstream from a promoter sequence, which promoter sequence is controlled by an inducing agent; a Cre recombinase sequence with expression controlled by the inducing agent; and, wherein the transposase sequence is upstream from a reverse oriented first Lox sequence and downstream from a second Lox sequence, which second Lox sequence is forward oriented between the promoter sequence and the transposase sequence; and, wherein the stop sequence is bracketed by a pair of forward oriented Lox sequences; 2) providing an expression transposon nucleic acid construct comprising: a transposon sequence encoding a protein sequence of interest flanked by inverted terminal repeats (ITRs), which ITRs are the binding target of the transposase; and, a binding site (BS) for the first transcriptional activator upstream from the ITRs; 3) applying the inducing agent to the cell, thereby inducing expression of Cre; 4) inverting the transposase to forward orientation by a CRE/Lox inversion, thus allowing expression of the transposase; 5) inserting the transposon at one or more safe harbor loci (SHL); and, 6) expressing the protein of interest in the host cell from the one or more SHL sites” (p. 70-71), which is Claim 13 of the instant application. Therefore, Claim 13 is anticipated by Ngo.
Regarding Claim 14, Ngo teaches in Claim 14 of Ngo “The method of claim 13, wherein the promoter sequence is a TRE3G promoter and the inducing agent is Dox/rtTA” (p. 71), which is Claim 14 of the instant application. Therefore, Claim 14 is anticipated by Ngo.
Regarding Claim 15, Ngo teaches in Claim 15 of Ngo “The method of claim 13, further comprising controlling a copy number of inserted transposons by adjusting the concentration of the inducing agent” (p. 71), which is Claim 15 of the instant application. Therefore, Claim 15 is anticipated by Ngo.
Regarding Claim 16, Ngo teaches in Claim 16 of Ngo “The method of claim 13, further comprising selecting host cells for blasticidin (Bsd) or II puromycin (Puro) resistance” (p. 71), which is Claim 16 of the instant application. Therefore, Claim 16 is anticipated by Ngo.
Regarding Claim 17, Ngo teaches in Claim 17 of Ngo “The method of claim 13, further comprising enabling the insertion of the transposon by knock-in into the SHL by AAV and CRISPR enzymes Cas9, Cas12a (Cpfl), Cas12b, CasX, or Cas Y” (p. 72), which is Claim 17 of the instant application. Therefore, Claim 17 is anticipated by Ngo.
Regarding Claim 18, Ngo teaches in Claim 18 of Ngo “The method of claim 13, wherein the protein of interest is an antibody protein” (p. 72), which is Claim 18 of the instant application. Therefore, Claim 18 is anticipated by Ngo.
Regarding Claim 19, Ngo teaches in Claim 19 of Ngo “The method of claim 13, wherein the SHL is a SHL of Table 3” (p. 72), which is Claim 19 of the instant application. Table 3 is on pages 28-30 of the instant application is identical to Table 3 on pages 28-30 of Ngo. Therefore, Claim 19 is anticipated by Ngo.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Krishna Nuggehalli Ravindra whose telephone number is (571)272-2758. The examiner can normally be reached M-Th, alternate F, 8a-5p est.
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/K.N.R./Examiner, Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636