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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-9, in the reply filed on 11-5-25 is acknowledged.
Claims 10-12 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11-5-25.
Claim Objections
The numbering in claim 1 should use “a)”, “b)”, “c)” or i), ii), iii) instead of 1, 2, 3 for ease of reference so as not to be confused with claim 1, 2, 3….
The abbreviation of NF-κB RE in claim 1 should be spelled out before being abbreviated.
The phrase “the step of preparing [ ]by inserting” in step 1 of claim 1 can be more simply written as ---inserting an exogenous nucleic acid sequence encoding nuclear factor kappa light chain enhancer response element (NF-κB RE) and an exogenous nucleic acid sequence encoding a marker protein into a targeting vector---. Applicants did not insert an entire “reporter gene” including its promoter and 3’ elements; they just inserted the coding sequence.
The phrases “the step of preparing [ ]by inserting” in steps 2-5 of claim 1 can be more simply written as above.
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. 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 phrase “locus of X over P1” in claim 2 can be deleted because the structures/function of “loxP” sites were well-known. Just use “loxP” sites.
Claim 2 item c) should clearly refer to ---the nucleotide sequence encoding NF-κB RE---.
It is unclear how/whether the sequences encoding luciferase and tdTomato in items e) and g) of claim 2 are the reporter genes in claim 1 (although applicants do not teach putting the whole luciferase and tdTomato genes including their promoters and 3’ elements into the targeting vector).
Claim 8 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. It requires mating the mouse of claim 1 with a Cre mouse, 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. 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.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 8. 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.
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 1-9 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 making the 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]
1) a step of preparing a targeting vector by inserting a gene cassette including a nucleotide sequence encoding NF-KB RE (nuclear factor kappa-light-chain-enhancer of activated B cells response element) and a reporter gene into a mouse ROSA26 locus;
2) a step of preparing a mouse embryonic stem cell clone by inserting the targeting vector prepared in step 1) into mouse embryonic stem cells;
3) a step of inserting the mouse embryonic stem cell clone prepared in step 2) into the blastocyst isolated from a wild-type mouse;
4) a step of implanting the blastocyst into which the clone of step 3) is inserted into the uterus of a surrogate mouse; and
5) a step of preparing a heterozygous mouse by mating the mouse born from the surrogate mouse of step 4) with a wild-type mouse.
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. 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.
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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.
It is unclear how/whether the sequences encoding luciferase and tdTomato in items e) and g) of claim 2 are the reporter genes in claim 1. Applicants do not teach putting the whole luciferase and tdTomato genes including their promoters and 3’ elements into the targeting vector, so the concept in claim 2 lacks written description.
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 and a nucleic acid sequence encoding a reporter protein (see Fig. 1A and 1B).
Claim 8 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. It requires mating the mouse of claim 1 with a Cre mouse, 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. 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, or tdTomato or that luciferase are expressed. Much clarification will be required, but those mice after recombination in claim 8 have different structures and functions that those obtained in claim 7. Therefore, the mice in claim 8 lack written description as broadly claimed.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 8. 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.
Enablement
Claims 1-9 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 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.
It is unclear how/whether the sequences encoding luciferase and tdTomato in items e) and g) of claim 2 are the reporter genes in claim 1. Applicants do not teach putting the whole luciferase and tdTomato genes including their promoters and 3’ elements into the targeting vector, so the concept in claim 2 lacks written description.
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 and a nucleic acid sequence encoding a reporter protein (see Fig. 1A and 1B).
Claim 8 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. It requires mating the mouse of claim 1 with a Cre mouse, 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. 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, or tdTomato or that luciferase are expressed. Much clarification will be required, but those mice after recombination in claim 8 have different structures and functions that those obtained in claim 7.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 8. 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.
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 1-9.
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 1-9 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.
Claim 1 is missing essential elements, steps, and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 1. Claim 1 is missing obtaining a genetically modified mouse whose genome comprises an exogenous transgene. It missing the fact that 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 missing the fact that the exogenous sequences encoding NF-κB RE or the reporter gene are operably linked to a promoter. It missing the fact that the genetically modified mouse expresses neomycin but not NF-κB RE or the reporter genes.
The metes and bounds of an ROSA26 “locus” in claim 2 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 is missing the fact that the mouse is genetically modified mouse and has a genome comprising an exogenous transgene. It missing the fact that 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 missing the fact that the exogenous sequences encoding NF-κB RE or the reporter gene are operably linked to a promoter. It missing the fact that the genetically modified mouse expresses neomycin but not NF-κB RE, luciferase, and tdTomato. It is missing the fact that it is capable of recombination allowing expression of NF-κB RE, luciferase, and tdTomato.
In particular, claim 8 is missing essential elements for the “mouse model for bioimaging of inflammatory signals” as required in claim 1. It requires mating the mouse of claim 1 with a Cre mouse, 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. 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.
Claim 9 is missing steps and reagents for obtaining a “mouse model for bioimaging of inflammatory signals” as required in claim 8. 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.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 7 is 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 and 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. Therefore, claim 1 is extremely broad and encompasses any mouse capable of bioimaging of inflammatory signals because none of the transgenes in steps 1-5 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.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claim 7 is 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 and 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. Therefore, claim 1 is extremely broad and encompasses any mouse capable of bioimaging of inflammatory signals because none of the transgenes in steps 1-5 necessarily remain.
Zhu taught bioluminescence imaging in a genetically modified mouse whose genome comprises NF κB activation-luciferase coding sequences inserted into its genome.
Zhu did not teach inserting the NF-κB-luciferase sequence into the 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.
Thus, Applicants' claimed invention as a whole is prima facie obvious in the absence of evidence to the contrary.
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
Those of ordinary skill in the art at the time of filing would have been motivated to insert the transgene into the Rosa26 gene because it is a “safe-harbor” for transgenes.