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 .
Claim 8 has been canceled. Claims 1-7, 9-12 are pending.
Applicant's arguments filed 5-11-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicants elected Group I, claims 1-9, without traverse in the reply filed on 11-5-25. Claims 10-12 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-7, 9 are under consideration.
Claim Objections
Step d) of claim 1 does not have a nexus with the mouse ES cells made in step a) of claim 1. Step d) requires obtaining offspring from the surrogate mouse but does not require they are developed from the mouse ES cells obtained in step a).
The offspring mice do not have the “gene cassette” in the Rosa26 gene as required in step d) of claim 1 because the cassette has homology arms that are part of the naturally occurring Rosa26 gene. Only items ii)-vi) in step a) are inserted into the endogenous Rosa26 gene.
Step f) in claim 1 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene.
Step f) in claim 1 does not clearly set forth using a genetically modified mouse whose genome comprises a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter.
Step g) in claim 1 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene and a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter.
It is unclear how the mouse obtained in step g) is a “mouse model for bio-imaging of inflammatory signals”.
The term UBC in claim 2 should be spelled out before being abbreviated.
Claim 4 does not make sense because the cells are treated with a reagent that binds the selection marker; the selection marker is expressed in the cell and is not added to the cell by “treating” as claimed.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 7. It requires the mouse expresses Cre “in certain cells or tissues”, but it does not set forth any function of that mating, any change in the genetic makeup of the mouse, or any function that is lost or imparted to the mouse. The claim does not require obtaining a genetically modified mouse whose genome comprises an exogenous transgene encoding Cre operably linked to a tissue specific promoter. It does not require the mouse has a genome comprising a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence encoding NF-κB RE and an exogenous nucleic acid sequence encoding a reporter gene AND an exogenous nucleic acid sequence encoding Cre operably linked to a tissue specific promoter. It does not require the exogenous sequences encoding NF-κB RE or the reporter gene are operably linked to a promoter or have a new configuration after recombination. It does not result in a genetically modified mouse that expresses Cre, NF-κB RE, luciferase and tdTomato or that expression of luciferase is only in specific tissues as a result of a tissue specific promoter driving expression of Cre.
Claim Rejections - 35 USC § 112
Claims 1-7, 9 remain 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 making a mouse model for bioimaging of inflammatory signals as required in claim 1.
Claim 1 is drawn to a method for preparing a mouse model for bio-imaging of inflammatory signals comprising the following steps:[AltContent: rect]
a) introducing a targeting vector into mouse embryonic stem cells, wherein the targeting vector comprises a gene cassette comprising from 5' to 3':
(i) a first nucleic acid sequence from a ROSA26 locus;
(ii) a first promoter operably linked to a transcription stop cassette flanked by loxP sites;
(iii) a nuclear factor kappa-light-chain-enhancer of activated B cells response element (NF-icB RE) operably linked to a second promoter operably linked to a nucleic acid sequence encoding a first reporter protein;
(iv) a third promoter operably linked to a nucleic acid sequence encoding a second reporter protein;
(v) a polyadenylation (poly A) signal;
(vi) a selection marker gene; and
(vii) a second nucleic acid sequence from a ROSA26 locus;
b) a step of inserting the mouse embryonic stem cells clone prepared in after step a) into a blastocyst isolated from a wild-type mouse;
c) implanting the blastocyst into the uterus of a surrogate mouse;
d) selecting an offspring born from the surrogate mouse, wherein the offspring comprises the gene cassette at a ROSA26 locus; and
e) mating the offspring with a wild-type mouse;
f) selecting a heterozygous offspring from the mating in e) that comprises the gene cassette at a ROSA26 locus;
g) mating the heterozygous offspring with a genetically engineered mouse expressing Cre recombinase specifically in certain cells or tissues; and
h) selecting an offspring from the mating in g) that comprises the gene cassette at a ROSA26 locus and expresses Cre recombinase specifically in certain cells or tissues, thereby obtaining the mouse model for bio-imaging of inflammatory signals.
The method of claim 1 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. Step a) does not result in the genome of the mouse ES cells being genetically modified. Step d) of claim 1 does not have a nexus with the mouse ES cells made in step a) of claim 1. Step d) requires obtaining offspring from the surrogate mouse but does not require they are developed from the mouse ES cells obtained in step a). Step d) requires the offspring have “the gene cassette at a Rosa26 locus”; however, “the gene cassette” has homology arms that are part of the naturally occurring Rosa26 gene and are not incorporated into the endogenous Rosa26 gene, i.e. only items ii)-vi) in step a) are “at a Rosa26 locus”. Step f) in claim 1 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene. Step f) in claim 1 does not clearly set forth using a genetically modified mouse whose genome comprises a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter. Step g) in claim 1 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene and a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter.
Most importantly, it is unclear how the mouse obtained in step g) is a “mouse model for bio-imaging of inflammatory signals”. The structures/functions of the mouse obtained in claim 1 (despite making a vector and putting into a mouse ES cell) are still broad because the vector may not integrate, because wild-type mice can be used for bioimaging of inflammatory signals, and because genetically modified mice that are different that those made by applicants can be used for bioimaging of inflammatory signals.
Zhu (React. Oxyg. Species, Apex 2017, Vol. 4, No. 12, pg 382-388) taught bioluminescence imaging in a genetically modified mouse whose genome comprises NF κB activation-luciferase coding sequences inserted into its genome.
Lee (KR 20200108159) taught inserting a coding sequence of interest into the Rosa26 gene.
The specification teaches “targeting vector constructed by inserting a tissue-specific NF-xB (nuclear factor kappa-light- chain-enhancer of activated B cells) reporter cassette into the mouse ROSA26 gene” (pg 6; Fig. 1A). The “LSL cassette” within the targeting vector is a polyA “transcription stop” flanked by loxP sites.
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The reporter cassette is in Fig. 1B:
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Fig. 1C shows the final ROSA26 gene:
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Neomycin is expressed in the mouse ES cells, but NF-κB RE, luciferase, and tdTomato are not expressed because of the “LSL” polyA “transcription stop”. The ES cells were cloned, inserted into a blastocyst, implanted into a surrogate such that offspring were born (pg 16, 1st and 2nd full paragraphs; pg 16-17 “Confirmation of mouse gene by Southern blotting”.
The paragraph bridging pg 17-18 teaches: “Since the mouse for bio-imaging of inflammatory signals prepared in Example < 1-1 > contains a stop codon marked by a loxP site on the gene cassette structure, the mouse can express luciferase according to the activity of NF-KB, an inflammation-related factor, only when the stop codon is removed by mating with a mouse expressing Cre recombinase”.
The mice of example 1 were crossed with a mouse expressing Cre under the control of a lysozyme 2 (Lyz2) promoter which is specific for myeloid cells (pg 18, lines 4-8).
Inflammation was specifically induced using PSA in one ear of mice obtained after crossing and luciferase was specifically expressed in the specific ear (which resulted in removal of the LSL cassette and expression of NF-κB RE, luciferase, and tdTomato) (pg 18, 2.2). Colitis was induced using DSS in the mice and luciferase was strongly expressed in the large intestine (pg 19, 2.3). Macrophages from bone marrow were differentiated in vitro and expressed luciferase (pg 19, last para). Macrophages treated with LPS and optionally BAY 11-7082 (an NF-κB inhibitor), and luciferase expression was determined to be suppressed by the addition of BAY 11-7082 (pg 20-21, 2.4).
Example 3 (pg 21) describes crossing the mice with mice expressing “Cre recombinase specifically in hepatocytes”. Albumin-Cre mice that specifically express Cre in hepatocytes were well-known (Postic, J. Biol. Chem., 1999, Vol. 274, No. 1, pg 305-315). Pg 21-22, section 3.2, describes inducing hepatitis in mice obtained from the cross using LPS and D-gal. Luciferase was detected specifically in liver of the mice (pg 22).
The specification does not correlate the intricate transgene specifically inserted into the ROSA26 gene to any other configuration as broadly encompassed by claim 1 or 7. Nor does it correlate the mouse that expresses neomycin but not NF-κB RE, luciferase, or tdTomato to any expression of any transgene as broadly encompassed by claim 1. The function of the mouse, the tissue specific expression of Cre, and as a result, the tissue specific expression of luciferase or tdTomato is completely missing from the claim. It is also unclear how tissue specific expression of luciferase or tdTomato after tissue specific recombination makes the mouse a model of bioimaging of inflammatory signals.
Claim 7 is drawn to a mouse model for bioimaging made by the method of claim 1. The mouse model “for bio-imaging of inflammatory signals” in claim 7 is a product-by-process dependent upon claim 1. Claim 7 does not require the final mouse has any genetic modification of any gene for reasons set forth above.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 7. It requires the mouse expresses Cre “in certain cells or tissues”, but it does not set forth any function of that mating, any change in the genetic makeup of the mouse, or any function that is lost or imparted to the mouse. The claim does not require obtaining a genetically modified mouse whose genome comprises an exogenous transgene encoding Cre from the mating. It does not require the mouse has a genome comprising a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence encoding NF-κB RE and an exogenous nucleic acid sequence encoding a reporter gene AND an exogenous nucleic acid sequence encoding Cre operably linked to a tissue specific promoter. It does not require the exogenous sequences encoding NF-κB RE or the reporter gene are operably linked to a promoter or have a new configuration after recombination. It does not result in a genetically modified mouse that expresses Cre, NF-κB RE, luciferase and tdTomato or that expression of luciferase is only in specific tissues as a result of a tissue specific promoter driving expression of Cre. Much clarification will be required, but those mice after recombination in claim 9 each have different structures and functions than each other. Therefore, the mice in claim 9 lack written description as broadly claimed.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Enablement
Claims 1-7, 9 remain 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 a method of making a genetically modified mouse whose genome comprises a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence comprising from 5’ to 3’: a ubiquitous promoter, a stop cassette, a nucleic acid sequence encoding NF-κB RE, a nucleic acid sequence encoding a marker protein operably linked to a minimal TA promoter, and a nucleic acid sequence encoding a neomycin operably linked to a promoter, wherein the mouse expresses neomycin but not NF-κB RE or the marker protein, does not reasonably provide enablement for claim 1 or 7 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 the mouse model for bioimaging of inflammatory signals as required in claim 1.
Claim 1 is recited above and is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. The claim does not require obtaining a genetically modified mouse whose genome comprises an exogenous transgene. It does not require the mouse has a genome comprising a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence encoding NF-κB RE and an exogenous nucleic acid sequence encoding a reporter gene. It does not require the exogenous sequences encoding NF-κB RE or the reporter gene are operably linked to a promoter. It does not result in a genetically modified mouse that expresses neomycin but not NF-κB RE, luciferase, or tdTomato. The structures/functions of the mouse obtained in claim 1 (despite making a vector and putting into a mouse ES cell) are extremely broad because the vector may not integrate, because wild-type mice can be used for bioimaging of inflammatory signals, and because genetically modified mice that are different that those made by applicants can be used for bioimaging of inflammatory signals.
Zhu (React. Oxyg. Species, Apex 2017, Vol. 4, No. 12, pg 382-388) taught bioluminescence imaging in a genetically modified mouse whose genome comprises NF κB activation-luciferase coding sequences inserted into its genome.
Lee (KR 20200108159) taught inserting a coding sequence of interest into the Rosa26 gene.
The specification teaches “targeting vector constructed by inserting a tissue-specific NF-xB (nuclear factor kappa-light- chain-enhancer of activated B cells) reporter cassette into the mouse ROSA26 gene” (pg 6; Fig. 1A). The “LSL cassette” within the targeting vector is a polyA “transcription stop” flanked by loxP sites (see Fig. 1A above).
The reporter cassette is in Fig. 1B (see above). Fig. 1C shows the final ROSA26 gene (see above). Neomycin is expressed in the mouse ES cells, but NF-κB RE, luciferase, and tdTomato are not expressed because of the “LSL” polyA “transcription stop”. The ES cells were cloned, inserted into a blastocyst, implanted into a surrogate such that offspring were born (pg 16, 1st and 2nd full paragraphs; pg 16-17 “Confirmation of mouse gene by Southern blotting”.
The paragraph bridging pg 17-18 teaches: “Since the mouse for bio-imaging of inflammatory signals prepared in Example < 1-1 > contains a stop codon marked by a loxP site on the gene cassette structure, the mouse can express luciferase according to the activity of NF-KB, an inflammation-related factor, only when the stop codon is removed by mating with a mouse expressing Cre recombinase”.
The mice of example 1 were crossed with a mouse expressing Cre under the control of a lysozyme 2 (Lyz2) promoter which is specific for myeloid cells (pg 18, lines 4-8).
Inflammation was specifically induced using PSA in one ear of mice obtained after crossing and luciferase was specifically expressed in the specific ear (which resulted in removal of the LSL cassette and expression of NF-κB RE, luciferase, and tdTomato) (pg 18, 2.2). Colitis was induced using DSS in the mice and luciferase was strongly expressed in the large intestine (pg 19, 2.3). Macrophages from bone marrow were differentiated in vitro and expressed luciferase (pg 19, last para). Macrophages treated with LPS and optionally BAY 11-7082 (an NF-κB inhibitor), and luciferase expression was determined to be suppressed by the addition of BAY 11-7082 (pg 20-21, 2.4).
Example 3 (pg 21) describes crossing the mice with mice expressing “Cre recombinase specifically in hepatocytes”. Albumin-Cre mice that specifically express Cre in hepatocytes were well-known (Postic, J. Biol. Chem., 1999, Vol. 274, No. 1, pg 305-315). Pg 21-22, section 3.2, describes inducing hepatitis in mice obtained from the cross using LPS and D-gal. Luciferase was detected specifically in liver of the mice (pg 22).
The specification does not correlate the intricate transgene specifically inserted into the ROSA26 gene to any other configuration as broadly encompassed by claim 1 or 7. Nor does it correlate the mouse that expresses neomycin but not NF-κB RE, luciferase, or tdTomato to any expression of any transgene as broadly encompassed by claim 1. The function of the mouse, the tissue specific expression of Cre, and as a result, the tissue specific expression of luciferase or tdTomato is completely missing from the claim. It is also unclear how tissue specific expression of luciferase or tdTomato after tissue specific recombination makes the mouse a model of bioimaging of inflammatory signals.
Claim 7 is drawn to a mouse model for bioimaging made by the method of claim 1. The mouse model “for bio-imaging of inflammatory signals” in claim 7 is a product-by-process dependent upon claim 1. Claim 7 does not require the final mouse has any genetic modification of any gene for reasons set forth above.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 7. It requires the mouse expresses Cre “in certain cells or tissues”, but it does not set forth any function of that mating, any change in the genetic makeup of the mouse, or any function that is lost or imparted to the mouse. The claim does not require obtaining a genetically modified mouse whose genome comprises an exogenous transgene encoding Cre from the mating. It does not require the mouse has a genome comprising a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence encoding NF-κB RE and an exogenous nucleic acid sequence encoding a reporter gene AND an exogenous nucleic acid sequence encoding Cre operably linked to a tissue specific promoter. It does not require the exogenous sequences encoding NF-κB RE or the reporter gene are operably linked to a promoter or have a new configuration after recombination. It does not result in a genetically modified mouse that expresses Cre, NF-κB RE, luciferase and tdTomato or that expression of luciferase is only in specific tissues as a result of a tissue specific promoter driving expression of Cre. Much clarification will be required, but those mice after recombination in claim 9 each have different structures and functions than each other. Therefore, the mice in claim 9 are not enabled as broadly claimed.
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 the mice as broadly encompassed by claims 1-7, 9.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Indefiniteness
Claims 1-7, 9 remain 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.
Claim 1 is missing essential elements, steps, and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. The method of claim 1 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. Step a) does not result in the genome of the mouse ES cells being genetically modified. Step d) of claim 1 does not have a nexus with the mouse ES cells made in step a) of claim 1. Step d) requires obtaining offspring from the surrogate mouse but does not require they are developed from the mouse ES cells obtained in step a). Step d) requires the offspring have “the gene cassette at a Rosa26 locus”; however, “the gene cassette” has homology arms that are part of the naturally occurring Rosa26 gene and are not incorporated into the endogenous Rosa26 gene, i.e. only items ii)-vi) in step a) are “at a Rosa26 locus”. Step f) in claim 1 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene. Step f) in claim 1 does not clearly set forth using a genetically modified mouse whose genome comprises a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter. Step g) in claim 1 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene and a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter. Most importantly, it is unclear how the mouse obtained in step g) is a “mouse model for bio-imaging of inflammatory signals”. The structures/functions of the mouse obtained in claim 1 (despite making a vector and putting into a mouse ES cell) cannot be determined. Therefore, those of skill would not know when they were infringing on the claim.
The metes and bounds of an ROSA26 “locus” in claim 1 are unclear. First, “locus” is singular, and “loci” is plural (Wikipedia definition of “locus”, 2023; National Human Genome Res. Institute definition of “locus”, 2023). Second, locus (singular) is a position in space or an address on a chromosome. Third, the specification does not define a ROSA26 “locus” (singular) as a ROSA26 gene (which must have a plurality of nucleotides) or as a plurality of nucleotides encoding a ROSA26 protein. Fourth, the specification is limited to replacing a plurality of endogenous nucleotides (at a plurality of contiguous “loci” (plural)) with a plurality of exogenous nucleotides. The specification does teach the exogenous nucleotides are present at a single locus, position, or address on the chromosome as claimed. Replacing pluralities of nucleotides is not replacing a nucleotide at a single locus as claimed. Fifth, the concept claimed does not accurately set forth the genetic modification because the addresses and positions of the human and endogenous ROSA26 nucleotides may change because of differences in the length of the exogenous and endogenous proteins and coding sequences. Accordingly, use of “ROSA26 locus” makes the claim unclear.
The mouse of claim 7 is missing essential elements for the “mouse model for bioimaging of inflammatory signals” obtained by the method of claim 1. Claim 7 does not result in the genome of the mouse being genetically modified. Claim 7 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene. Claim 7 does not clearly set forth using a genetically modified mouse whose genome comprises a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter. Claim 7 does not clearly set forth obtaining a genetically modified mouse whose genome comprises a heterozygous copy of the cassette in an endogenous Rosa26 gene and a nucleic acid sequence encoding Cre recombinase operably linked to a tissue specific promoter. Most importantly, it is unclear how the mouse obtained in claim 7 is a “mouse model for bio-imaging of inflammatory signals”. The structures/functions of the mouse obtained in claim 7 (despite making a vector and putting into a mouse ES cell) cannot be determined. Therefore, those of skill would not know when they were infringing on the claim.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 7. It requires the mouse expresses Cre “in certain cells or tissues”, but it does not set forth any function of that mating, any change in the genetic makeup of the mouse, or any function that is lost or imparted to the mouse. The claim does not require obtaining a genetically modified mouse whose genome comprises an exogenous transgene encoding Cre from the mating. It does not require the mouse has a genome comprising a replacement of an endogenous nucleic acid sequence encoding ROSA26 with an exogenous nucleic acid sequence encoding NF-κB RE and an exogenous nucleic acid sequence encoding a reporter gene AND an exogenous nucleic acid sequence encoding Cre operably linked to a tissue specific promoter. It does not require the exogenous sequences encoding NF-κB RE, luciferase, or tdTomato are operably linked to a promoter or have a new configuration after recombination. It does not result in a genetically modified mouse that has the LSL cassette removed or that it expresses Cre, NF-κB RE, luciferase, or tdTomato in specific tissues.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Applicants argue “locus” refers to a non-coding region. Applicants’ argument is not persuasive because it is unfounded. Use the term “gene”.
Claim Rejections - 35 USC § 102
Claim 7 remains rejected under 35 U.S.C. 102a1 as being anticipated by Zhu (React. Oxyg. Species, Apex 2017, Vol. 4, No. 12, pg 382-388).
Claim 7 is drawn to a mouse model for bioimaging made by the method of claim 1. The mouse model “for bio-imaging of inflammatory signals” in claim 7 is a product-by-process dependent upon claim 1. Claim 7 does not require the final mouse has any genetic modification of any gene, i.e. a genetically modified mouse whose genome comprises an endogenous Rosa26 gene comprising an exogenous nucleic acid sequence encoding NF-κB RE operably linked to a promoter operably linked to a nucleic acid sequence encoding a reporter protein (see Fig. 1A and 1B). Claim 1 does not impart any specific structures or functions into the mouse of claim 7. Therefore, claim 7 is extremely broad and encompasses any mouse capable of bioimaging of inflammatory signals because none of the transgenes in claim 1 necessarily remain.
Zhu taught bioluminescence imaging in a genetically modified mouse whose genome comprises NF κB activation-luciferase coding sequences inserted into its genome. This is all that is required to meet the structural and functional limitations of the mouse in claim 7.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above. Applicants fail to acknowledge the product-by-process of claim 7 is extremely broad because claim 1 never requires a mouse whose genome comprises the constructs in Fig. 1. Claim 7 encompasses a genetically modified mouse whose genome comprises an exogenous nucleic acid sequence encoding NF κB activation-luciferase coding sequences located anywhere which was taught by Zhu.
Claim Rejections - 35 USC § 103
Claim 7 remains rejected under 35 U.S.C. 103 as being unpatentable over Zhu (React. Oxyg. Species, Apex 2017, Vol. 4, No. 12, pg 382-388) in view of Lee (KR 20200108159).
Claim 7 is drawn to a mouse model for bioimaging made by the method of claim 1. The mouse model “for bio-imaging of inflammatory signals” in claim 7 is a product-by-process dependent upon claim 1. Claim 7 does not require the final mouse has any genetic modification of any gene, i.e. a genetically modified mouse whose genome comprises an endogenous Rosa26 gene comprising an exogenous nucleic acid sequence encoding NF-κB RE operably linked to a promoter operably linked to a nucleic acid sequence encoding a reporter protein (see Fig. 1A and 1B). Claim 1 does not impart any specific structures or functions into the mouse of claim 7. Therefore, claim 7 is extremely broad and encompasses any mouse capable of bioimaging of inflammatory signals because none of the transgenes in claim 1 necessarily remain.
Zhu taught bioluminescence imaging in a genetically modified mouse whose genome comprises a nucleic acid sequence comprising NF-κBRE operably linked to a promoter operably linked to a luciferase coding sequence.
Zhu did not teach inserting the nucleic acid sequence into a ROSA26 gene as encompassed by claim 7.
However, Lee taught inserting coding sequences into the ROSA26 gene (Examples).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a genetically modified mouse whose genome comprised an exogenous nucleic acid sequence encoding NF κB activation-luciferase coding sequences as described by Zhu and inserting them into the ROSA26 gene as described by Lee. Those of ordinary skill in the art at the time of filing would have been motivated to insert the sequence into the ROSA26 gene because it is a “safe harbor”. This is all that is required to meet the structural and functional limitations of the mouse in claim 7.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above. Applicants fail to acknowledge the product-by-process of claim 7 is extremely broad because claim 1 never requires a mouse whose genome comprises the constructs in Fig. 1. Claim 7 encompasses a genetically modified mouse whose genome comprises an endogenous Rosa26 gene comprsing an exogenous nucleic acid sequence encoding NF κB activation-luciferase coding sequences which was taught by the combined teachings of Zhu and Lee.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
Prosecution Insights