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 .
Claims 1-3, 5, 6, 8, 12, 13, 23, 28, 29 have been canceled. Claims 4, 7, 9-11, 14-22, 24-27 are pending.
Election/Restrictions
Applicant’s election without traverse of Group IV, claims 4, 7-11, 14, 15, in the reply filed on 8-10-26 is acknowledged.
Groups I and VIII has been recombined with Group IV.
Claim 17 has been withdrawn.
Claims 4, 7, 9-11, 14-16, 18-22, 24-27 are under consideration as they relate to:
Group I) a mammalian cell whose genome comprises modified BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes, wherein the cell exhibits reduced expression of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1;
Group IV) a mammalian cell whose genome comprises modified BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1 genes and an exogenous nucleic acid sequence encoding a product of interest, wherein the cell exhibits reduced expression of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1, and expresses the product of interest; and
Group VIII) a method of using the cells of Group IV to produce the product of interest.
Claim 4 as originally filed fails to capture the lowest common denominator for the inhibited genes required to have the desired function, i.e. improved expression of an exogenous nucleic acid sequence (exogenous mAb3 expression in CHO cells on pg 39, line 32, through pg 40, line 1; pg 155, lines 16-19; pg 156, Table 8). Claim 2 (now canceled) lists all the possible genes for inhibition, but claim 4 fails to use such a format. Claim 16 (withdrawn) also has a list of possible genes for inhibition. The genes in claim 2 and 16 all appear to have a role in apoptosis (pg 51, lines 16-18). Each of items a)-rrrr) as set forth in claim 4 as originally filed are not to be construed as patentably distinct.
Claim objections
The means by which the cell of claim 4 has been modified are irrelevant because they do not impart any structures/functions to the cells that distinguish them from cells made by other means (having the same structures/functions). Invoking product-by-process language in claim 4 does not further limit the structures/functions of the claim beyond what already occurs, i.e. modified BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1 genes and incorporation of an exogenous nucleic acid sequence into the genome, and reduced expression of BAX,…PPT1 and expression of the product of interest.
Claim 4 fails to say the cell is isolated.
Claim 4 can be written more clearly as ---An isolated mammalian cell whose genome comprises a modified BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1 gene and an exogenous nucleic acid sequence encoding a product of interest, wherein the cell exhibits reduced expression of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1 and expresses the product of interest---.
Claim 4 as originally filed fails to capture the lowest common denominator for the inhibited genes required to have the desired function, i.e. improved expression of an exogenous nucleic acid sequence. The format in claim 2 (now canceled) lists all the possible genes for inhibition. Claim 16 (withdrawn) also has a list of possible genes for inhibition. The format in claims 2 or 16 are preferred if embodiments other than item c) in claim 4 as originally filed are to be pursued.
Claim 7 can be written more clearly ---wherein the reduced expression is no detectable expression---.
Claim 9 can be written more clearly as ---wherein the product is a protein---.
Claim 10 can be written more clearly as ---wherein the protein is an antibody or antigen-binding fragment thereof---.
Claim 11 can be written more clearly as ---wherein the exogenous nucleic acid sequence is integrated into the genome at targeted location---.
Claim 14 can be written more clearly as ---wherein the cell is a CHO cell---.
Claim 16 should be dependent upon claim 4 and can be written more clearly as ---A method of producing a product of interest, the method comprising:
culturing the mammalian cell of claim 4; and
recovering the product of interest from the cultured mammalian cell---.
Claims 18 and 19 should be canceled because they does not further limit claim 16 or 4.
Claim 20 should be canceled because claim 4 requires the cell contains an exogenous nucleic acid.
Claim 21 can be written more clearly as ---wherein the exogenous nucleic acid sequence is integrated into the genome at targeted location---.
Claim 22 can be written more clearly as ---wherein the exogenous nucleic acid sequence is integrated into the genome at a random location---.
Claim 24 can be written more clearly as ---wherein the product is a protein---.
Claim 25 can be written more clearly as ---wherein the protein is an antibody or antigen-binding fragment thereof---.
Claim 26 can be written more clearly as ---further comprising purifying or formulating the product of interest---.
Claim 27 can be written more clearly as ---wherein the cell is a CHO cell---.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
Claims 4, 7, 9-11, 14-16, 18-22, 24-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification lacks written description for any mammalian cell with expression of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 reduced/eliminated as broadly encompassed by claim 4 other than an isolated mammalian cell whose genome comprises inactivated BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes, wherein the cell does not express BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1. The claim encompasses a cell in vivo or in vitro; however, the specification and the art at the time of filing is limited to inactivating BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes in mammalian cells in vitro. The claim encompasses cells that have been treated with a compound or iRNA or whose genomes comprise a genetic modification that results in reduced/eliminated expression of the genes; however, the elected subject matter is limited to a cell whose genome comprises genetically modified genes. The claim encompasses cells with any genetic modification that reduces or eliminates expression of the genes; however, the specification is limited to inactivating the genes (Example 1, pg 138). The specification does not correlate inactivating the genes to genetically modifying the genes such that slight or modest reduced expression occurs. Accordingly, the concept lacks written description for the full breadth of genetic modifications and function of those modifications encompassed by claim 4.
The specification lacks written description for a mammalian cell “transfected to express a recombinant product of interest” as broadly encompassed by claim 4 other than a cell whose genome comprises an exogenous nucleic acid sequence encoding a product of interest. The phrase “to express” is an intended use and does not necessarily have to occur. The claim fails to clearly set forth the genome of the cell is genetically modified with an exogenous nucleic acid sequence or that the sequence encodes a product of interest. Accordingly, the concept lacks written description for the full breadth of “transfected to express” encompassed by claim 4.
The specification lacks written description for the comparison in the last 3 lines of claim 4. The claim requires expression of the genes is “reduced or eliminated relative to the expression of the endogenous products in an unmodified cell”; however, the control must have wild-type BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes and express wild-type levels of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 which is missing from the claim. If the claim ends up saying expression of the genes are inactivated, then no comparison is required.
The specification lacks written description for the “process” portion of the “product” in the last 2 lines of claim 4. The claim requires “the modification comprises applying a nuclease-assisted and/or nucleic acid targeting each expression product in said grouping” which is grammatically indiscernible. The means by which the cell of claim 4 has been modified are irrelevant because they do not impart any structures/functions to the cells that distinguish them from cells made by other means (having the same structures/functions). Invoking product-by-process language in claim 4 does not further limit the structures/functions of the claim beyond what already occurs, i.e. modified BAX,… …and PPT1 genes and incorporation of an exogenous nucleic acid sequence into the genome, and reduced expression of BAX,…and PPT1 and expression of the product of interest. Moreover, the specification and the art at the time of filing are limited to using CRISPR technology or homology vectors for inactivating genes which require specific reagents and “process” steps that are missing from claim 4. The phrase “nuclease-assisted [ ] targeting” fails to capture the steps/reagents of CRISPR technology. The phrase “nucleic acid targeting” fails to capture the steps/reagents of homology vector technology. Accordingly, the concept lacks written description.
Enablement
Claims 4, 7, 9-11, 14-16, 18-22, 24-27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an isolated mammalian cell whose genome comprises a modified BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1 gene and an exogenous nucleic acid sequence encoding a product of interest, wherein the cell exhibits reduced expression of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1 and expresses the product of interest, does not reasonably provide enablement for the claims as broadly written. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The specification does not enable making/using any mammalian cell with expression of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 reduced/eliminated as broadly encompassed by claim 4 other than an isolated mammalian cell whose genome comprises inactivated BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes, wherein the cell does not express BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, or PPT1. The claim encompasses a cell in vivo or in vitro; however, the specification and the art at the time of filing is limited to inactivating BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes in mammalian cells in vitro. The claim encompasses cells that have been treated with a compound or iRNA or whose genomes comprise a genetic modification that results in reduced/eliminated expression of the genes; however, the elected subject matter is limited to a cell whose genome comprises genetically modified genes. The claim encompasses cells with any genetic modification that reduces or eliminates expression of the genes; however, the specification is limited to inactivating the genes (Example 1, pg 138). The specification does not correlate inactivating the genes to genetically modifying the genes such that slight or modest reduced expression occurs. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make/use cells within the full breadth of claim 4.
The specification does not enable making/using a mammalian cell “transfected to express a recombinant product of interest” as broadly encompassed by claim 4 other than a cell whose genome comprises an exogenous nucleic acid sequence encoding a product of interest. The phrase “to express” is an intended use and does not necessarily have to occur. The claim fails to clearly set forth the genome of the cell is genetically modified with an exogenous nucleic acid sequence or that the sequence encodes a product of interest. Given the lack of guidance in the specification taken with the art at the time of filing, it would have required those of skill undue experimentation to determine how to make/use cells within the full breadth of “transfected to express” encompassed by claim 4.
The specification does not enable the comparison in the last 3 lines of claim 4. The claim requires expression of the genes is “reduced or eliminated relative to the expression of the endogenous products in an unmodified cell”; however, the control must have wild-type BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes and express wild-type levels of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 which is missing from the claim. If the claim ends up saying expression of the genes are inactivated, then no comparison is required.
The specification does not enable the “process” portion of the “product” in the last 2 lines of claim 4. The claim requires “the modification comprises applying a nuclease-assisted and/or nucleic acid targeting each expression product in said grouping” which is grammatically indiscernible. The means by which the cell of claim 4 has been modified are irrelevant because they do not impart any structures/functions to the cells that distinguish them from cells made by other means (having the same structures/functions). Invoking product-by-process language in claim 4 does not further limit the structures/functions of the claim beyond what already occurs, i.e. modified BAX,… …and PPT1 genes and incorporation of an exogenous nucleic acid sequence into the genome, and reduced expression of BAX,…and PPT1 and expression of the product of interest. Moreover, the specification and the art at the time of filing are limited to using CRISPR technology or homology vectors for inactivating genes which require specific reagents and “process” steps that are missing from claim 4. The phrase “nuclease-assisted [ ] targeting” fails to capture the steps/reagents of CRISPR technology. The phrase “nucleic acid targeting” fails to capture the steps/reagents of homology vector technology. Accordingly, the concept is not enabled.
Indefiniteness
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, 7, 9-11, 14-16, 18-22, 24-27 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.
The concept of a mammalian cell “transfected to express a recombinant product of interest” in claim 4 makes the claim indefinite. The phrase “to express” is an intended use and does not necessarily have to occur. The claim fails to clearly set forth the genome of the cell is genetically modified with an exogenous nucleic acid sequence or that the sequence encodes a product of interest which are essential to the cells.
The comparison in the last 3 lines of claim 4 makes the claim indefinite. The claim requires expression of the genes is “reduced or eliminated relative to the expression of the endogenous products in an unmodified cell”; however, the control must have wild-type BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes and express wild-type levels of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 which is missing from the claim. If the claim ends up saying expression of the genes are inactivated, then no comparison is required.
The “process” portion of the “product” in the last 2 lines of claim 4 makes the claim indefinite. The claim requires “the modification comprises applying a nuclease-assisted and/or nucleic acid targeting each expression product in said grouping” which is grammatically indiscernible. It is unclear how the means by which the cell of claim 4 have impart any structures/functions to the cells that distinguish them from cells made by other means (having the same structures/functions). It is unclear how product-by-process language in claim 4 further limits the structures/functions of the claim beyond what already occurs, i.e. modified BAX,… …and PPT1 genes and incorporation of an exogenous nucleic acid sequence into the genome, and reduced expression of BAX,…and PPT1 and expression of the product of interest. Moreover, the specification and the art at the time of filing are limited to using CRISPR technology or homology vectors for inactivating genes which require specific essential reagents and “process” steps that are missing from claim 4. The phrase “nuclease-assisted [ ] targeting” fails to capture the essential steps/reagents of CRISPR technology. The phrase “nucleic acid targeting” fails to capture the essential steps/reagents of homology vector technology. Accordingly, the concept makes the claim indefinite.
Claims 16, 18-22, 24-27 are indefinite because they are dependent upon claim 1 which has been canceled.
Assuming claims 18 and 19 are intended to be dependent upon claim 4, they are indefinite because the scope of inactivated genes listed in claims 18 and 19 is broader than those in claim 4. Therefore, claims 18 and 19 cannot further limit claim 4.
Cost (Biotech. & Bioengineering, 2009, Vol. 105, No. 2, pg 330-340) taught mammalian cells with inactivated BAX and BAK genes; however, the art at the time of filing did not reasonably teach or suggest a mammalian cell whose genome comprises genetically modified BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 genes, wherein expression of BAX, BAK, ICAM1, SIRT1, MYC, GGTA1, CMAH, LPL, LPLA2, and PPT1 is reduced in the cell as required in claim 4.
Conclusion
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
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