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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 31, 2025 has been entered.
Application Status
Applicant’s amendments filed July 31, 2024, amending claims 1, 11, 13-14, 27, 46, 57 and 68 and cancelling claim 12 is acknowledged. Accordingly, claims 1-11, 13-14, 27, 46, 57 and 68 are pending and under examination.
Withdrawn Rejections
The amendments to the claims 14, 46 and 57 requiring a lack of expression of one or more tRNAs and the foreign nucleic acid to contain codons that would have been recognized by the missing tRNA overcomes the §102 rejections over Issacs and Liebl, and the §101 rejection for subject matter eligibility.
Any other rejection or objection not reiterated herein has been overcome by amendment. Applicant's amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Interpretations
For claims 46, 57 and 68 directed to cells, “an altered cell” and a “cell [that] is genomically recoded” are interpreted as a product-by-process limitations that are not limited by the steps in the process to arrive at the final cell. See MPEP 2113. The cells will be examined based on the structure that would result if a cell is generically “altered” or is “recoded”. The Specification does not define “genomically recoded” but does indicate that “[c]ells may be genomically recoded as is known in the art by creating unassigned codons. Unassigned codons do not have a cognate tRNA associated with the codon.” (page 3, ¶1). Additionally, the Specification teaches that cells can be recoded by eliminating a release factor (RF) rendering a stop codon unassigned (page 6). Therefore “genomically recoded cells” are ones that lack a tRNA or a release factor thereby rendering either a sense codon or a stop codon unassigned.
As indicated in the previous office action, “A canonical codon” is interpreted as a standard codon according to the generally-accepted and nearly universal genetic code (https://en.wikipedia.org/wiki/Genetic_code).
“A toxic polypeptide” and “a toxic protein” are interpreted as any polypeptide that when expressed reduces the growth, either directly or indirectly, of the cell that expresses it.
Claim Objections
Claims 27, 46 and 68 are objected to because of the following informalities:
Claims 27, 46 and 68 recite “wherein the foreign nucleic acid sequence comprising the canonical codons whose recognition by the one or more cognate tRNAs is absent due to the lack of expression of the one or more cognate tRNAs”, which does not make grammatical sense, since the wherein clause lacks a verb. The following is suggested for the above wherein clause: ‘wherein the foreign nucleic acid sequence comprises the canonical codons whose recognition by the one or more cognate tRNAs is absent due to the lack of expression of the one or more cognate tRNAs.”
Claim 46 also recites “wherein the cells within the population of cells comprises a foreign…” in lines 4-5, which is also grammatically correct. The claim should recite “wherein the cells within the population of cells comprise[[s]] a foreign…”
Appropriate correction is required.
Claim Rejections - 35 USC § 101 - AIA
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.
Claims 46, 57 and 68 are 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). This is a new rejection.
The claims are drawn to “a population of genomically recoded cells” and “a population of altered cells”. The specification does not provide a limiting definition of a cell, and does not expressly exclude cells within a human organism. The Specification does disclose that the recoded cell can be a human cell (page 8, ¶1). Thus, the term “cell” could reasonably be interpreted as encompassing cells within a human organism, which is non-statutory subject matter. The rejection may be obviated by requiring that the cell be a non-human cell.
Response to Arguments - § 101
Applicant’s arguments on page 8-10, filed July 31, 2025, with respect to the rejection(s) of claim 47 under §101 as directed to a judicial exception have been fully considered in view of the claim amendments, and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made in view of Section 33(a) of the America Invents Act.
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.
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 1-7, 13-14, 27, 46, 57 and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Isaacs (US 20210123064 A1, priority to at least November 30, 2020; of record). Claims 14 and 57 are evidenced by Genbank2 (Gen Bank: M62654.1, Aequorea victoria green-fluorescent protein mRNA, complete eds, https://www.ncbi.nlm.nih.gov/nuccore/155662, [retrieved July 3, 2024]; of record). This is an updated rejection necessitated by amendment.
Claims 46, 57 and 68 are directed to altered cells, whereas claims 1-11, 13 and 27 are directed to methods of making the altered cells. For the sake of logic, the claims directed to cells (46, 57 and 68) are addressed first.
Regarding claim 46, Isaacs teaches recoded E. coli cells (i.e., a population of cells) that lack expression of RF1 which recognizes the UAG stop codon (Fig 1B; [0022]), leaving UAG an unassigned codon in the cell ([0022], [0064]). Isaacs teaches introducing plasmids (i.e., foreign nucleic acids) encoding GFP (i.e., a polypeptide) in the RF1- E. coli cells ([0245]). Isaacs teaches the pUAG-GFP plasmid has a UAG codon to stop translation of the GFP polypeptide (i.e., the foreign nucleic acid sequence comprises the canonical codon whose recognition by the release factor RF1 is absent due to the lack of expression of RF1 ([0245]). Isaacs teaches the genomically recoded cells were transformed with the plasmid and grown (i.e., the population of genomically recoded cells is grown from a genomically recoded cell including the foreign nucleic acid sequence of canonical codons encoding the polypeptide) ([0245]). Isaacs teaches that genetic recoding to create unassigned codons can also be done by eliminating or mutating tRNA genes instead of release factors ([0022], [0064]; Fig 1A). Isaacs teaches that an eliminated codon/tRNA from a host can be utilized by an organism to reduce expression of genes on foreign DNA that arrive via horizontal gene transfer ([0081], [0085]).
Isaacs does not teach in a single embodiment a recoded cell lacking expression of a tRNA cognate to one or more unassigned codons to cells and comprising a foreign nucleic sequence comprising canonical codons encoding a polypeptide.
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have deleted one of the tRNA genes in Isaacs’s E. coli cells instead of the RF1 gene to create an unassigned codon for the foreign GFP plasmid. It would have amounted to the simple substitution of one means of recoding cells by another known means to yield predictable results. Isaacs indicates that creating unassigned nonsense codons (i.e., UAG) and creating an unassigned sense codon (i.e., a tRNA codon) are two means to recode a cell to prevent horizontal gene transfer like transformation or phage infection from killing cells. Because the prior art recognizes the equivalence of deleting an RF gene and deleting a tRNA gene for the purpose of recoding cells to create an unassigned codon, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP 2144.06.II.
Regarding claim 57, the teachings of Isaacs regarding the recoded RF1- E. coli cells comprising GFP-encoding plasmids are recited as for claim 46. As noted above, Isaac’s pUAG-GFP includes a UAG codon as the stop codon at the 3’ end of the coding sequence. Genbank2 teaches GFP normally comprises a UAA codon at the end of the coding sequence (page 1 indicates that the eds ends at nucleotide position 2523; page 2 indicates the last the three nucleotides of the eds are TAA, which when transcribed would be UAA). Therefore, the pUAG-GFP plasmid in Isaacs is a foreign nucleic acid sequence which has been recoded (UAA>UAG) to include the unassigned UAG codon in the RF1 E. coli cell. Issacs teaches determining the protein produced by the pUAG-GFP plasmid in the absence of RF1 ([0245], Table 2). Issacs teaches that the polypeptide produced from pUAG-GFP has additional amino acids attached at the C-terminal end, which indicates that the presence of the unassigned UAG reduced or otherwise prevented expression of the intended polypeptide, i.e., GFP-His6 (Table 2).
The obviousness of having deleted one of the tRNA genes in Isaacs’s E. coli cells instead of the RF1 gene to create an unassigned sense codon is recited as for claim 46. It would have been obvious to one skilled in the art that including the unassigned codon in the polypeptide coding sequence for which the cognate tRNA gene was deleted would also prevent or otherwise reduce the expression of the polypeptide based on Isaac’s results with the unassigned stop codon. The skilled artisan would expect either that the ribosome would stall once the unassigned sense codon was encountered, or a different tRNA would restart the stall. In either case, the result would either be reduced polypeptide expression or the expression of a polypeptide other than what was intended/coded by the plasmid.
Regarding claim 68, the teachings of Isaacs regarding the recoded RF1- E. coli cells comprising GFP-encoding plasmids are recited as for claim 46. Isaacs also teaches providing the RF1- E. coli cells infected with lambda phage DNA (i.e., foreign nucleic acid) and transformed with a plasmid encoding prfA (i.e., an expression plasmid encoding the release factor RF1) (Fig. 5A-B; [0026]). Issacs teaches providing the plasmid encoding the missing RF1 factor, the cells are able to translate the foreign DNA (Fig. 5B).
The obviousness of deleting a tRNA gene instead of the RF1 gene in the E. coli cells comprising foreign DNA is recited above for claim 46. It also would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have provided the missing tRNA gene on a plasmid to the obvious cells with the deleted tRNA genes for the purpose of controlling transgene translation. It would have amounted to a simple combination of known steps to recode cells to test the prevention and then allowance of expression of the genes on foreign DNA for horizontal transfer. The skilled artisan would have been motivated to do so to test the model put forward by Issacs that prevention and then permissiveness of horizontal gene transfer can also occur through deletion of tRNA genes and subsequent reintroduction of the tRNA genes as was shown for deletion of an RF1 factor that recognizes UAG. The skilled artisan would have predicted that the tRNA genes could be reintroduced to the recoded cells because it would have merely required standard genetic engineering methods known in the art and Issacs demonstrates providing previously deleted genes on a plasmid.
Regarding claims 1 and 3-4, the teachings of Isaacs regarding the RF1- E. coli cells (i.e., microbial cells, bacterial cells) comprising GFP-encoding plasmids are recited as for claim 46. Isaacs teaches introducing the pUAG-GFP plasmid (i.e., foreign nucleic acid sequences of canonical codons encoding a polypeptide) into the RF1- E. coli cells and growing them to sufficient quantities to isolate the polypeptide (i.e., wherein the cell is grown to produce a population of cells including the foreign nucleic acid sequence) ([0245]). Isaacs also teaches the RF1- cells comprising pUAG-GFP (i.e., cells with an unassigned codon) had a doubling time of at least 50 minutes, indicating that a population of those cells had been produced (Fig 3A). Isaacs teaches that in the absence of the RF1 release factor, the proteins/peptides that were produced from the pUAG-GFP plasmid were a result of frameshifting, tmRNA targeting, and near-cognate suppression ([0248]), indicating that production of the GFP polypeptide itself was prevented.
The obviousness of deleting a tRNA gene instead of the RF1 gene in the E. coli cells comprising foreign DNA is recited above for claim 46. The skilled artisan would have expected that a GFP having a canonical codon for which there was no tRNA to recognize it would prevent expression of the GFP because Issacs teaches unassigned codons prevent expression of intended cloned gene having the unassigned codon.
Regarding claims 2, 5-6, Isaacs also teaches that the recoded cells can be eukaryotes, including yeast cells, plant cells, mammalian cells and human cells ([0019]). Isaacs teaches that CHO cells (i.e., a eukaryotic cell) are well known in the art to be useful for producing polypeptides ([0114], [0116]). Isaacs teaches that HEK293 cells and HUVEC cells (i.e., human cells) are useful for expression of recombinant proteins ([0116]).
It would have also been obvious to one skilled in the art before the effective filing date of the claimed invention to have deleted a tRNA gene in a eukaryotic, yeast or human cell to generate unassigned codons in a cell and then introduce a transgene comprising the unassigned codon. It would have amounted to applying an obvious method to known cell types to yield predictable results. The skilled artisan would have predicted that genomic recoding for the purpose of controlling expression of a transgene could be performed in the claimed cell types, and been motivated to do so, because Isaacs suggests it.
Regarding claims 7, Isaacs teaches the recoded cells comprising pUAG-GFP coding for GFP (i.e., a protein).
Regarding claim 13, the obviousness of deleting a tRNA gene instead of the RF1 gene in the E. coli cells comprising foreign DNA is recited above for claims 1 and 46. Isaacs also teaches providing the RF1 gene on a plasmid and restoring GFP expression ([0270]). Isaacs teaches that providing the RF1 deleted gene in trans allows the researcher to control the level of RF1 to study ribosome stalling and control in the level of resistance to horizontal gene transfer (Example 4, [0267]-[0274]).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have provided the deleted tRNA gene to the cell in the method rendered obvious for claim 1. It would have amounted to known means of genetic complementation to yield predictable results. The skilled artisan would have been motivated to provide an inducible cognate tRNA gene on a plasmid to the tRNA negative cells, in the same fashion that Isaacs provided the inducible RF1 gene on a plasmid, for the purpose of recovering non-resistant viral particles or understanding the mechanism of ribosome stalling. The skilled artisan would have predicted that the tRNA gene could be provided to the cells in trans because Isaacs demonstrates such a method for the RF1 release factor, which is also a genetically encoded codon-recognition factor.
Regarding claims 14, the teachings of Isaacs and Genbank2 regarding the RF1- E. coli cells (i.e., microbial cells, bacterial cells) comprising the recoded GFP-encoding plasmids are recited as for claims 1, 46 and 57. Briefly, Isaacs teaches introducing the pUAG-GFP plasmid (i.e., providing a foreign nucleic acid sequences of canonical codons encoding a polypeptide in which the stop codon was altered to produce one or more unassigned codons within the cell) into the RF1- E. coli cells (i.e., genomically recoded cells wherein the cell lacks a release factor that recognizes the canonical UAG codon) and growing them to sufficient quantities to isolate the polypeptide (i.e., wherein the cell is grown to produce a population of cells including the foreign nucleic acid sequence) ([0245]). Isaacs teaches that in the absence of the RF1 release factor, the proteins/peptides that were produced from the pUAG-GFP plasmid were a result of frameshifting, tmRNA targeting, and near-cognate suppression ([0248]), indicating that production of the GFP polypeptide itself was prevented. Isaacs teaches that genetic recoding to create unassigned codons can also be done by eliminating or mutating tRNA genes instead of release factors ([0022], [0064]; Fig 1A). Isaacs teaches that an eliminated codon/tRNA from a host can be utilized by an organism to reduce expression of genes on foreign DNA that arrive via horizontal gene transfer ([0081], [0085]).
The obviousness of deleting a tRNA gene instead of the RF1 gene in the E. coli cells comprising foreign DNA is recited above for claims 1 and 46. The skilled artisan would have expected that a GFP having a canonical codon for which there was no tRNA to recognize it would prevent expression of the GFP because Issacs teaches unassigned codons prevent expression of intended cloned gene having the unassigned codon.
Regarding claim 27, the teachings of Isaacs regarding the RF1- E. coli cells comprising GFP-encoding plasmids are recited as for claims 1 and 46. Briefly, Isaacs teaches expressing GFP or mutated GFP (i.e., a polypeptide) from pUAG-GFP (i.e., the foreign nucleic acid) (Fig 3C). Isaacs teaches providing the pUAG-GFP plasmid to the RF1- E. coli cells (i.e., recoded cells that cannot recognize the unassigned UAG due to lack of expression of RF1) by transformation ([0245]). Additionally, Isaacs teaches providing the RF1- E. coli cells infected with lambda phage DNA (i.e., foreign nucleic acid to produce polypeptides in the cell) with a plasmid encoding prfA under the influence of the VA-inducible promoter (i.e., an expression plasmid encoding the release factor RF1 under the influence of an inducible promoter) (Fig. 5A-B; [0026]). Isaacs teaches growing the RF1- cells with the pUAG-GFP plasmid ([0245]) or the lambda phage ([0026]).
The obviousness of deleting a tRNA gene instead of the RF1 gene in the E. coli cells comprising foreign DNA that is altered in a codon for the deleted tRNA is recited above for claims 1 and 46.
Claims 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Isaacs (US 20210123064 A1, priority to at least November 30, 2020; of record) as applied to claims 1-7, 13-14, 27, 46, 57 and 68, and in further view of Lajoie (Lajoie et al., Science (2013), 342: 357-360; of record). This is an updated rejection necessitated by amendment.
The teachings of Isaacs are recited above and applied as for claims 1-7, 13-14, 27, 46, 57 and 68. Isaacs also teaches infecting the RF1- E. coli cells (i.e., genomically recoded organisms, GROs) with lambda phage DNA (i.e., introducing into the cell a foreign nucleic acid to produce polypeptides in the cell) (Fig 4D; [0261]). Isaacs teaches that phage propagation measured as plaque forming units (PFUs) was greatly reduced in RF1- E. coli cells (i.e., reduced bacterial cell toxicity) compared to the wildtype strain ECNR2 (Fig 4D, [0025], [0261]). Isaacs teaches that doubling time is determined by a change in optical density at 600 nm (i.e., cell growth rate) ([0024]).
Isaacs does not expressly teach that phage proteins are toxic. Isaacs does not expressly teach that deletion of a tRNA gene cognate to a canonical codon would prevent expression of the toxic polypeptide thereby reducing toxicity in the cell.
Similar to Isaacs, Lajoie teaches recoding E. coli cells by eliminating the RF1 release factor (Fig 1). Lajoie teaches that RF1- cells have increased resistance to the T7 bacteriophage (i.e., reduce toxicity of the phage polypeptide) (page 359, ¶2-3). Lajoie teaches that viruses rely on their host to express proteins necessary for virus propagation (page 359, ¶2). Lajoie teaches that hosts with recoded genetic codes mistranslate viral proteins (i.e., prevent production of a polypeptide that is toxic to the host cell) (page 359, ¶2).
Regarding claims 8, and 10-11, the obviousness of deleting a tRNA gene instead of the RF1 gene in the E. coli cells comprising foreign DNA that is altered in a codon for the deleted tRNA is recited above for claims 1 and 46. It also would have been obvious to one skilled in the art before the effective filing date of claimed invention that the obvious method of deleting a tRNA gene would reduce the toxicity of the invading phage foreign DNA by reducing the expression of the toxic phage proteins. Isaacs teaches that removing machinery that recognizes a codon reduced phage plaque formation in Isaacs’s RF1- E. coli cells. Lajoie teaches that the reduced phage plaque formation (i.e., reduced toxicity) results in reduced phage protein expression and production. Therefore, the art recognizes that reduced toxicity of phage proteins is due to lower expression of the phage genes. Because Isaacs teaches that deleting a tRNA gene such that codons become unassigned is also a means to reduce horizontal gene transfer, of which phage-mediated transduction is one type, the skilled artisan would predict that the method rendered obvious for claim 1 would also reduce toxicity of the phage proteins by reducing its expression.
Regarding claim 9, Isaacs teaches that phage propagation was reduced by nearly 100% (i.e., by at least 90%) in RF1- E. coli cells compared to the wildtype strain ECNR2 (Fig 4D, [0025], [0261]). Because Lajoie teaches that phage propagation is toxic to the cells, and Isaacs teaches that cell growth rate can be measured by optical density, the skilled artisan would have expected that the growth rate of cells infected with phage could be measured and would have been at least at least 1% or at least 90% lower than the growth rate of a wild-type cell.
Response to Arguments - § 103
Applicant explains 1) the claims were amended to recite a population of cells grown from a cell that has been genomically recorded and includes a foreign nucleic acid so that the foreign nucleic acid is not expressed during the growing into a population of cells, and 2) the advantages of the claimed methods and cells (Remarks, ¶ spanning pages 13-14). Applicant then argues that none of Issacs, GenBank2 or Lajoie teaches or suggests 1) cells lacking expression of one or more tRNAs, 2) unassigned codons reduces or prevents expression of the foreign nucleic acid sequence into the polypeptide, or 3) growing the genomically recoded cells without expression of the foreign nucleic acid (Remarks, page 14, ¶2-4). This argument has been fully considered but is not persuasive because Isaacs does teach and/or suggest each element. As indicated in the rejection above Isaacs teaches 2) recoding a cell by deleting an RF1 and provides a foreign nucleic acid encoding GFP with the UAG stop codon (i.e., the unassigned codon), and then demonstrates the effect of having the unassigned stop codon on production of the polypeptide – namely GFP had additional amino acids, and so, in effect, “the polypeptide” encoded by the nucleic acid was not expressed as coded. Isaacs teaches 3) transforming the RF1-negative cells with the GFP-UAG-encoding plasmid and growing up the population of cells. Then Isaacs 1) suggests that the same effect could be brought about by deleting a tRNA gene instead of deleting the RF1. Because Isaacs teaches that cells can also be recoded by deleting tRNA genes that recognize a sense codon, in a similar manner as deleting a release factor that recognizes a stop codon, it would have been obvious to do so with a reasonable expectation of success. Finally, the skilled artisan would predict that if a tRNA that recognizes a codon is deleted, any mRNA comprising that codon would not be expressed since the ribosome would stall at the unassigned codon. This conclusion is based on the understanding of protein translation, which is taught in most introductory undergraduate biology courses. See e.g., Chapter 15: Genes and Proteins. In Biology 2e, Houston, TX: Open Stax, Published March 28, 2018; Fig 15.16 and 15.18.
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 46, 57 and 68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 40 of copending Application No. 17611010 (reference application). Claim 57 is evidenced by OpenStax (Chapter 15: Genes and Proteins. In Biology 2e, Houston, TX: Open Stax, Published March 28, 2018). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Copending claim 40 recites A population comprising a plurality of the genetically engineered bacterial organisms, wherein the genetically engineered bacterial organisms each comprise: (i) at least one genetically engineered codon (i.e., a recoded codon), wherein the at least one genetically engineered codon comprises a sense codon, (ii) at least one deletion of a nucleic acid sequence encoding a transfer RNA cognate to the sense codon (i.e., lacks expression of one or more tRNAs cognate to one or more canonical codons) and (iii) at least one exogenous nucleic acid sequence encoding a therapeutic polypeptide or portion thereof, wherein the at least one exogenous nucleic acid sequence comprises the at least one genetically engineered codon (i.e., wherein the foreign nucleic acid sequence comprises the canonical codons whose recognition by the one or more cognate tRNAs is absent due to the lack of expression of the one more cognate tRNAs). The copending claim does not recite that the population of cells is grown from a genomically recoded cell; however, the recited clause is interpreted as a product-by-process clause. The claim is examined based on the product of the claimed process, which is recited in examined claim 46 before the product-by-process clause. The structure of the population of cells in examined claims 46 and 68 and copending claim 40 are not distinct as each of the claims require lack of a tRNA expression and the presence of a polypeptide-encoding nucleic acid that comprises a codon that would have been recognized by the missing tRNA.
Regarding examined claim 57, it would have been obvious to one skilled in the art that including the unassigned codon in the polypeptide coding sequence for which the cognate tRNA gene was deleted in copending claim 40 would also prevent or otherwise reduce the expression of the polypeptide based on the basic understanding in the art of protein synthesis as taught in OpenStax (Fig 15.16 and 15.18). The skilled artisan would expect either that the ribosome would stall once the unassigned sense codon was encountered, or a different tRNA would restart the stall. In either case, the result would either be reduced polypeptide expression or the expression of a polypeptide other than what was intended/coded by the plasmid.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable.
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/CATHERINE KONOPKA/Examiner, Art Unit 1635