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
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 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.
Election/Restrictions
Applicant’s election without traverse of Invention I, Group I, claims 1-18, 20-22 and 29-33, in the reply filed on Jun. 8, 2028 is acknowledged.
Claims 1-50 remain pending in the current application, claims 19, 23-28, and 34-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
The requirement for the restriction of Inventions I-V is still deemed proper and is therefore made FINAL.
Claims 1-18, 20-22 and 29-33 have been considered on the merits.
Status of the Claims
Claims 1-50 are currently pending.
Claims 19, 23-28, and 34-50 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claim 1-18, 20-22 and 29-33 have been considered on the merits.
Drawings
The disclosure is objected to because of the following informalities:
The drawings are objected to because of the following informalities: in Fig. 19D the images are completely black.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: the use of trademarks.
The use of the terms Yokogawa CSU-1X® on pg. 28 lines 23, pg. 30 lines 10 and 17, pg. 48 line 7, pg. 48 line 7; iXon3® EMCCD camera on pg. 28 line 24, pg. 30 line 11, pg. 48 line 8-9; MetaMorph® software on pg. 28 line 25, pg. 30 line 12, pg. 48 line 10; Alexa Fluor® 568-phalloidin on pg. 28 line 31, pg. 31 line 27; Lipofectamine™ 2000 on pg. 29 lines 16, 20; BD FACS Aria™ III cell sorter on pg. 29 line 25; X-tremeGENE® 9 DNA on pg. 30 lines 2-3; MycoAlert® on pg. 30 line 5; Nikon® Eclipse® Ti-U confocal microscope on pg. 30 line 16; Photometrics Evolve® Delta EMCCD camera on pg. 30 lines 17-18; REPS® on pg. 39 line 29; Branson Sonifier® on pg. 46 line 29; Slide-A-Lyzer® membrane cassettes on pg. 47 line 3; Amicon® filter concentrators on pg. 47 line 20, which are a trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are 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 commercial marks.
Appropriate correction is required.
Claim Interpretation
Claim 1 is directed to a synthetic organelle containing two nucleic acid sequences. The claim is being interpreted to mean a composition containing the two described nucleic acids. This is based on the description in the published specification in 0005, which describes the synthetic organelle only containing the claimed two nucleic acid sequences. From the description in the specification and the prior art it is the proteins encoded by these nucleic acids form the synthetic organelles.
Claim Objections
The disclosure is objected to because of the following informalities: minor grammatical error in claims.
Claim 2 is objected to because of the following informalities: the first time an acronym is utilized in a claim-set, said acronym should be spelled out in its entirety followed by said acronym in parenthesis (e.g. SYNZIP1 (SZ1), SYNZIP2 (SZ2), thermo-sensitive CC (A) (TsCC(A)), thermo-sensitive CC (B) (TsCC(B))).
Claim 30 is objected to because of the following informalities: the first time an acronym is utilized in a claim-set, said acronym should be spelled out in its entirety followed by said acronym in parenthesis (e.g. reverse tetracycline-controlled transactivator (rtTA)).
Claim 31 objected to under 37 CFR 1.75 as being a substantial duplicate of claim 21. Claim 32 objected to under 37 CFR 1.75 as being a substantial duplicate of claim 22. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Appropriate corrections are appreciated.
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 4, 6, and 12 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.
In claim 4, the phrase "wherein when TsCC(A) interacts with TsCC(B), the client protein is sequestered in the synthetic organelle, and wherein when temperature is raised, the client protein is released from the synthetic organelle" lacks sufficient antecedent basis and renders the claim and its dependents indefinite. There are no proteins in the composition/synthetic organelle of claim 1 from which the claim depends from. Furthermore, the claims are to a composition and not to a method of releasing a cargo protein from an organelle. For the purposes of compact prosecution, this phrase will be interpreted to mean that nucleic acid encodes for a TsCC(A) and TsCC(B) that are capable of interacting when expressed.
In claim 6, line 2, the “wherein the RGG domains are RGG1, RGG2, and RGG3 from the Caenorhabditis elegans LAF-1 protein”, renders the claim and its dependents indefinite, since the LAF-1 protein does not have three different RRG domains. For the purposes of compact prosecution, this phrase in the claims will be interpreted to mean all three RGG domains are the RGG domain from Caenorhabditis elegans.
In claim 12, the phrase "wherein when the synthetic organelle is exposed to light, the photocleavable protein is cleaved and the client is released" lacks sufficient antecedent basis and renders the claim and its dependents indefinite. There are no proteins in the composition/synthetic organelle of claim 1 from which the claim depends from. Furthermore, the claims are to a composition and not to a method of releasing a client protein from an organelle by exposing the organelle to light. For the purposes of compact prosecution, this phrase will be interpreted to mean that nucleic acid encodes a photocleavable protein that is capable of being photocleaved when expressed and exposed to light.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 29 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 21. Claim 21 includes the nucleic acid of claim 1 which comprises a nucleic acid encoding a client protein, a second CC tag, and a second promoter. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 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.
Claims 1-2, 6, 10-11, 20-22, 31 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Schuster et al. (Nature Communications, 2018) (ref. of record) as evidenced by Agilent Technologies (“pET System Vector and Hosts: Instruction Manual”, 2017) and Rakhmawati et al. (Makara Journal of Science, 2018).
With respect to claim 1, Schuster teaches a synthetic organelle (Abstract). With respect to the first nucleic acid of claim 1 and claim 2, Schuster teaches a nucleic acid encoding a intrinsically disordered protein (IDP) containing two arginine/glycine-rich (RGG) protein domains and a coiled-coil pair tag that is SYNZIP1 and SYNZIP2 (SZ1 and SZ2) (high-affinity coiled-coil (CC) tag) (pg. 6 Col. 1 para. 2 and pg. 10 Col. 1 para. 5 and Fig. 1b).
Schuster is silent with respect to whether the nucleic acid contains a first promoter. However, Schuster teaches the genes were cloned into pET vectors in frame and cloned into pcDNA3.1 plasmids (pg. 10 Col. 1 para. 5 and pg. 11 Co 1 para. 4). However, the pET vector and pcDNA3.1 contain promoters as evidenced by Aligent Technologies and Rakhmawati. Agilent Technologies reports that the pET vector contains the T7 promoter and the gene of interest is cloned downstream of the promoter (pg. 6 para. 1). Rakhmawati reports that the pcDNA3.1 vector contains the cytomegalovirus (CMV) promoter and the gene of interest is cloned downstream of the promoter (pg. 6 para. 2).
Schuster does not explicitly teach the nucleic acid encoding three RGG protein domains. However, Schuster teaches the IDP containing a triplet RGG protein domain (pg. 2-3 bridging para. and Fig. 1b). Since Shuster teaches a sequence containing two RGG domains and a CC tag and teaches three RGG domains can be used, it would have been obvious to one of ordinary skill in the art to modify the nucleic acid sequence as taught by Schuster to include a nucleic acid encoding an IDP scaffold with three RGG domains, a CC tag and a promoter, since this would allow construction of an expression plasmid for a triplet RGG with a terminal CC tag for recruitment and concentration of cargo proteins conjugated to a corresponding paired CC tag. One of ordinary skill in the art would understand that this would improve or alter cargo recruitment or separation. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Schuster, since teaches three RGG domains can be used.
With respect to the second nucleic acid of claim 1 and claims 2 and 29, Schuster teaches the nucleic acid encoding a cargo protein, GFP or RFP (client protein) with a second CC tag that is SZ2 (Fig. 4b and Fig. 5).
Schuster is silent with respect to whether the nucleic acid contains a second promoter. However, Schuster teaches the genes were cloned into pET vectors in frame and cloned into pcDNA3.1 plasmids (pg. 10 Col. 1 para. 5 and pg. 11 Co 1 para. 4). However, the pET vector and pcDNA3.1 contain promoters as evidenced by Aligent Technologies and Rakhmawati. Agilent Technologies reports that the pET vector contains the T7 promoter and the gene of interest is cloned downstream of the promoter (pg. 6 para. 1). Rakhmawati reports that the pcDNA3.1 vector contains the cytomegalovirus (CMV) promoter and the gene of interest is cloned downstream of the promoter (pg. 6 para. 2).
With respect to claim 2, Schuster teaches SZ1 and SZ2 were sufficient to recruit and concentrate exogenous cargo proteins (pg. 6 Col. 1 para. 2-3).
With respect to claim 6, Schuster teaches the RGG domains are from the Caenorhabditis elegans LAF-1 protein (pg. 2 Col. 2 para. 2). Although, Schuster does teach whether the RGG is RGG1, RGG2 and RGG3, the LAF-1 protein does not contain 3 different RGGs as explained in the rejection under 35 U.S.C. §112 (b) and the claim is being interpreted to mean that all three RGG domains is the RGG domain from the Caenorhabditis elegans LAF-1 protein.
With respect to claims 10 and 11, Schuster teaches the second nucleic acid encoding eGFP or RFP (fluorescent tags) (Fig. 4b, Fig. 5 and pg. 10 Col. 1 para. 5 and pg. 11 Co 1 para. 4).
With respect to claims 20-22, 31 and 32, Schuster teaches the composition containing nucleic acids encoding double RGG domains in human embryonic kidney cells (HEK), HeLa cells (human cell line) and U2OS cells (Fig. 6e).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 3-5 are rejected under 35 U.S.C. 103(a) as being unpatentable over Schuster as evidenced by Agilent Technologies and Rakhmawati (as applied to claim 1 above), and further in view of Piraner et al. (ACS Synthetic Biology, 2019) (ref. of record) Piraner et al. (US 2021/0040161 A1, published Jul. 13, 2020) (Piraner ‘161) and Watanabe et al. (US 2014/0335539 A1).
The teachings of Schuster can be found in the previous rejection above.
Schuster does not teach the nucleic acid where the first CC tag is thermo-sensitive CC (A) (TsCC(A)) and the second CC tag is thermo-sensitive CC (B) (TsCC(B)) as recited in claim 3. Similarly, Schuster does not teach the nucleic acid where when TsCC(A) interacts with TsCC(B), the client protein is sequestered in the synthetic organelle and when the temperature is raised, the client protein is released from the synthetic organelle as recited in claim 4. As explained in the rejections under 35 U.S.C. §112 (b), claim 4 is being interpreted to mean that the nucleic acids encode for a TsCC(A) and a TsCC(B) that are capable of interacting. Likewise, Schuster does not teach the nucleic or amino acid sequences of the CC tag as recited in claim 5.
Piraner teaches a CC tag that is tsCC(A) and a CC tag that is tsCC(B) (temperature sensitive coiled-coil tag) that are capable of interacting (abstract and Fig. 2). Piraner discloses these temperature sensitive CC tags for the controllable association of cargo proteins (abstract, pg. 2258 Col. 1 para. 1 to Col. 2 para. 3). Piraner teaches the temperature sensitive coiled-coil tag is TlpA coils (pg. 2257 Col. 1 last para.). It is noted that in the published specification TlpA is used to engineer the tsCC (Fig. 1 and 0100). Piraner teaches that temperature as a mechanism for controlling biological signaling has several advantages over chemicals and light such as that it can be applied globally with simple heat sources or electromagnetic radiation, can be targeted locally deep within scattering media providing spatial and temporal resolution (pg. 1 para. 2).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster so that the CC tags are TsCC(A) and TsCC(B) tags for the benefit of temperature-specific association and release of target cargoes which would allow for improved control of protein release and/or activity such as conditionally controlling enzymatic activity as taught by Piraner. It would have been obvious to one of ordinary skill in the art to modify the composition/synthetic organelle taught by Schuster, to include or instead use TsCC(A) and TsCC(B) tags, as disclosed by Piraner, since Schuster discloses using paired CC tags to associate two macromolecule cargoes, and where the system may be used for temperature-dependent cargo assembly and release (pg. 3 Col. 1 para. 2 to pg. 4 Col. para. 1 and Fig. 1), and Piraner discloses temperature dependent CC tags used for assembly of cargo molecules. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Schuster, since Schuster teaches the composition where the nucleic acid encodes for CC tags and cargo proteins and Piraner teaches temperature sensitive CC tags, TsCC(A) and TsCC(B), for controlling cargo proteins using temperature.
Neither Schuster or Piraner teach the composition/synthetic organelle where the nucleic or amino acid sequences of the CC tag is one of those listed in claim 5.
However, Piraner ‘161 teaches dimerization thermoswitches (0003) and teaches a thermoswitch, SEQ ID NO. 66, has 100% homology with SEQ ID NO. 20 (see supplemental sequence search for Published Appl. for SEQ ID NO. 20). Piraner ‘161 further discloses these temperature sensitive CC tags for the controllable association of cargo moieties including proteins (abstract, 0107, 0115 and 0217-0218).
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Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster and Piraner so the amino acid sequence of the TsCC is that of SEQ ID No. 20 for the benefit of using a known sequence that confers the desired temperature sensitivity. It would have been obvious to one of ordinary skill in the art to make such a modification, since the sequence is simply the wild-type TlpA. For these reasons one of ordinary skill in the art would have had a reasonable expectation of success in making such modification to the nucleic acid sequence of Schuster and Piraner.
Schuster does not teach the nucleic acid where the first and/or second nucleic acid encodes a drug-induced dimerization domain as recited in claim 14. Schuster does not teach the nucleic acid where the drug-induced dimerization domain is FRB or FKBP as recited in claim 15. Schuster does not teach the nucleic acid where the drug-induced dimerization domain is encoded by the nucleotide sequence of any of SEQ ID NOs: 14 or 15; or comprises the amino acid sequence of any of SEQ ID NOs: 24 or 25 as recited in claim 16.
However, Piraner teaches chemically inducible dimerization domains such as FKBP/FRB have been used for a vast array of applications such as studying protein function and is effective in culture and for deep tissues (pg. 2256 para. 1).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster so that the first and/or second nucleotide encodes for chemically inducible dimerization domains including FKBP or FRB the benefit of studying protein function or controlling protein activity as taught by Piraner. It would have been obvious to one of ordinary skill in the art to modify the composition/synthetic organelle taught by Schuster, to include a chemically inducible dimerization domains including FKBP or FRB in nucleic acids, since Piraner discloses controlling proteins by chemically inducible dimerization domains. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Schuster, since Piraner teaches controlling proteins by chemically inducible dimerization domains is well known and effective.
Neither Schuster or Piraner teach the composition/synthetic organelle where the nucleic or amino acid sequences of the drug-induced dimerization domain is one of those listed in claim 16.
However, Watanabe teaches the human FRB domain of mTOR with SEQ ID NO. 21 (0194), which has 100% homology with SEQ ID NO. 15 (see supplemental sequence search for Published Appl. for SEQ ID NO. 15).
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Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster and Piraner so the nucleic acid sequence of the FRB domain is that of SEQ ID No. 15 for the benefit of using a known sequence that is a FRB domain. It would have been obvious to one of ordinary skill in the art to make such a modification, since the sequence is simply the wild-type FRB domain of mTOR. For these reasons one of ordinary skill in the art would have had a reasonable expectation of success in making such modification to the nucleic acid sequence of Schuster and Piraner.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 7 is rejected under 35 U.S.C. 103(a) as being unpatentable over Schuster as evidenced by Agilent Technologies and Rakhmawati (as applied to claim 1 above), and further in view of Arosio et al. (WO 2020/048996 A1).
The teachings of Schuster can be found in the previous rejection above.
Schuster does not teach the nucleic or amino acid sequences of the RGG domains as recited in claim 7.
However, Arosio teaches the wild-type RGG from Caenorhabditis elegans Laf-1, SEQ ID NO. 11, has 100% homology with SEQ ID NO. 16 (pg. 30 lines 15-20) (see supplemental sequence search for GeneSeq. for SEQ ID NO. 16).
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Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster so the amino acid sequence of the RGG is that of SEQ ID No. 16 for the benefit of using the known sequence of RGG from LAF-1. It would have been obvious to one of ordinary skill in the art to make such a modification, since the sequence is simply the wild-type RGG of LAF-1. For these reasons one of ordinary skill in the art would have had a reasonable expectation of success in making such modification to the nucleic acid sequence of Schuster.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 8, 9 and 33 are rejected under 35 U.S.C. 103(a) as being unpatentable over Schuster as evidenced by Agilent Technologies and Rakhmawati (as applied to claim 1 above), and further in view of Dzuricky et al. (US 2023/0086188 A1, priority to Mar. 4, 2020).
The teachings of Schuster can be found in the previous rejection above.
Schuster does not teach the nucleic acid where the client protein is an endogenous protein as recited in claim 8.
Schuster does not teach the nucleic acid where the client protein regulates a cellular function as recited in claim 9.
However, Dzuricky teaches peptide biopolymers with IDP sequences that have controlled phase separation based on their amino acid sequence, aromatic:aliphatic ratio, hydrophobicity, temperature, molecular weight and concentration (0005-0007). Dzuricky teaches the polypeptide with controlled reversible phase separation can be include an enzyme (0007). Dzuricky further teaches the composition modulates enzymatic, metabolic or physiological functions within cells or organisms (0008).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster so the client protein is an endogenous enzyme or a protein that regulates a cellular function for the benefit of being able to control the expression of such proteins within cells as taught by Dzuricky. It would have been obvious to one of ordinary skill in the art to make such a modification, since Dzuricky teaches similar fusion proteins containing IDP sequences fused to client proteins that are endogenous enzymes and those that control cellular function. For these reasons one of ordinary skill in the art would have had a reasonable expectation of success in making such modification to the nucleic acid sequence of Schuster so that the client protein encodes and enzyme or a protein that regulates cellular function.
Schuster does not teach the cell further containing a packaging plasmid and/or envelop plasmid as recited in claim 33.
Dzuricky teaches the nucleic acids encoding the peptides in a lentivirus particle (0009). Lentivirus particles would be readily be understood by one of ordinary skill in the art to include a packaging plasmid and an envelope plasmid.
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster so the cell contain a packaging plasmid and/or an envelope for the benefit of being able to introduce the exogenous nucleic acids to the cell as taught by Dzuricky. It would have been obvious to one of ordinary skill in the art to make such a modification, since Dzuricky teaches similar fusion proteins containing IDP sequences fused to client proteins that are endogenous enzymes and those that control cellular function which are encoding by nucleic acid in a lentivirus. For these reasons one of ordinary skill in the art would have had a reasonable expectation of success in making such modification to the nucleic acid sequence of Schuster so that the nucleic acid is in a lentivirus in the cell.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 12 is rejected under 35 U.S.C. 103(a) as being unpatentable over Schuster as evidenced by Agilent Technologies and Rakhmawati (as applied to claim 1 above), and further in view of Lu et al. (Chemical Science, May 31, 2021).
The teachings of Schuster can be found in the previous rejection above.
Schuster does not teach the nucleic acid where when the synthetic organelle exposed to light, the photocleavable protein is cleaved and the client is released as recited in claim 12. As explained in the rejections under 35 U.S.C. §112 (b), claim 12 is being interpreted to mean that nucleic acid encodes a photocleavable protein that is capable of being photocleaved when expressed and exposed to light.
Lu teaches photocleavable proteins that can be introduced into cells in the form of its corresponding gene to enable optogenetic control of biomolecular activities (abstract). Lu teaches nucleic acids encoding the photocleavable protein which is PhoCl1 and PhoCl 2F (abstract). Lu teaches that PhoCl can be used a versatile tool for covalent caging of a protein of interest and which can be subsequently activated irreversibly by light (pg. 9658 para. 2).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster so nucleic acid encodes a photocleavable protein such as PhoCl or PhoCl 2F for the benefit of being able to control the activity of such proteins within cells as taught by Lu. It would have been obvious to one of ordinary skill in the art to make such a modification, since Lu teaches caging proteins of interest by fusing a photocleavable protein sequence to the protein of interest or client protein to control the protein’s function. One of ordinary skill in the art would have had a reasonable expectation of success in making such modification to the nucleic acid sequence of Schuster so that the first and/or second nucleic acid encodes a photocleavable protein, since Lu teaches proteins of interested can be successfully tagged with photocleavable proteins.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 13 is rejected under 35 U.S.C. 103(a) as being unpatentable over Schuster as evidenced by Agilent Technologies and Rakhmawati (as applied to claim 1 above), and further in view of Chan et al. (US 2011/0083202 A1).
The teachings of Schuster can be found in the previous rejection above.
Schuster does not teach the nucleic acid where the photocleavable protein or fluorescent tag is encoded by a nucleotide sequence of any of SEQ ID NOs: 11, 12, or 13 as recited in claim 13.
However, Chan teaches the synthetic mCherry red fluorescent protein DsRed variant, SEQ ID NO. 104, has 100% homology with SEQ ID NO. 13 (pg. 69) (see supplemental sequence search for GeneSeq. for SEQ ID NO. 13).
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Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in art would have been motivated to modify the composition/synthetic organelle of Schuster so the nucleotide sequence of the fluorescent tag is that of SEQ ID No. 13 for the benefit of using the known sequence of a known fluorescent protein. It would have been obvious to one of ordinary skill in the art to make such a modification, since the sequence is simply the nucleotide sequence of mCherry. For these reasons one of ordinary skill in the art would have had a reasonable expectation of success in making such modification to the nucleic acid sequence of Schuster.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 17, 18 and 30 are rejected under 35 U.S.C. 103(a) as being unpatentable over Schuster as evidenced by Agilent Technologies and Rakhmawati (as applied to claim 1 above), and further in view of Romanova et al. (Biotechnology Journal, 2018).
The teachings of Schuster can be found in the previous rejection above.
Schuster does not teach the nucleic acid where the first promoter is an inducible promoter and the second promoter is a constitutive promoter as recited in claim 17. Schuster does not teach the nucleic acid where the second promoter is an endogenous promoter as recited in claim 18. Schuster does not teach the cell further containing a nucleic acid encoding a reverse tetracycline-controlled transactivator (rtTA) transactivator as recited in claim 30.
However, Romanova teaches that in mammalian cells transcription is a highly complex process and the promoter plays a pivotal role, therefore the choice of promoter and adjacent element can significantly influence transgene expression efficiency (pg. 1 para. 3). Romanova further teaches that there is substantial diversity in the structure and mechanism of action of promoters which impacts their ability to initiate transcription (pg. 2 para. 2). With respect to claims 17-18, Romanova teaches inducible promoters, constitutive promoters and endogenous promoters (abstract). Romanova teaches an advantage of inducible systems is controlling when the gene is expressed (pg. 7 Col. 1 para. 6). Romanova teaches constitutively active promotors are commonly used (pg. 2 Col. 1 para. 5, pg. 4 Col. 2 para. 3). Romanova teaches endogenous promotors are commonly used when transgene over-expression is not desired (pg. 5 Col. 1 para. 1). With respect to claim 33, Romanova teaches the Tet-On systems are well known and popular systems for control transgene expression and that rtTA transactivator is part of the Tet-On system (pg. 7 Col. 2 para. 2-3). Romanova teaches choosing suitable promoters to maximize transgene expression and long-term expression stability (abstract).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the nucleic acid taught by Schuster so that the first promoter is an inducible promoter, the second promoter is a constitutive promotor as recited in claim 17, so that the second promoter is an endogenous promoter as recited in claim 18, or so that the nucleic acid encodes a rtTA transactivator as recited in claim 30 for the benefit of control the level of expression and/or the timing of expression of the transgenes as taught by Romanova. It would have been obvious to one of ordinary skill in the art to modify the nucleic acids taught by Schuster to have appropriate promoters for the different transgenes depending on the desired level of expression and amount of control over expression needed, since it was known at the time to choose promoters according to the level of expression and control over transgene expression that was desired for the particular situation as taught by Romanova. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in modifying Schuster to include the claimed promoters and rtTA transactivator, since these promoter types and the rtTA transactivator were well-known to be used in transgene expression systems as taught by Romanova.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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