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 2, 4 have been canceled. Claims 1, 3, 5-8 remain pending and are pending and under consideration.
Applicant's arguments filed 12-17-25 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.
Term Confusion
The specification says the term PTGDS in claim 1 is prostaglandin D2 synthase (pg 2, para 5), also known as PGD2 synthase or PGD2. However, pg 8-10 discusses gene sequencing of the ptgds gene and shows SEQ ID NO: 11 (4299 bp) in paragraph 90. A sequence search of SEQ ID NO: 11 says it is in a rat prostaglandin-H-2 D-isomerase gene:
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For examination purposes is assumed “prostaglandin-H-2 D-isomerase” and “prostaglandin D2 synthase” are synonyms.
It is assumed prostaglandin D2 synthase is not the same as rat spleen prostaglandin D synthetase or brain prostaglandin D synthetase described by Urade (J. Biolog. Chem., 1987, Vol. 262, No. 8, pg 3820-3825).
Response to applicants’ comments
Applicants reiterate part of para 89 (pg 8) of the specification in addressing this issue (pg 5, 3rd full paragraph of the response filed 12-17-25), but applicants do not include the SEQ ID NOs in para 89 or 90. Applicants’ discussion under “Term Confusion” fails not address the fact that SEQ ID NO: 11 in paragraph 90 pulls up sequences named prostaglandin-H-2 D-isomerase. SEQ ID NO: 11 does not pull up anything called “prostaglandin D2 synthase”.
Applicants state the PTGDS sequence here is NCBI 25526, i.e. rat prostaglandin-H-2 D-isomerase (pg 5, end of 3rd full paragraph of the response filed 12-17-25), but NCBI 25526 is “prostaglandin D2 synthase”:
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RGD:3433 shows synonyms for prostaglandin-D synthase include prostaglandin-H2 D-isomerase .
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This confirms “prostaglandin-H-2 D-isomerase” and “prostaglandin D2 synthase” are synonyms.
Claim Objections
The phrase “designing two different sgRNAs, PTGDS-sgRNA1 and PTGDS-sgRNA2, wherein the two different sgRNAs target two different sequences of a rat Ptgds gene” in step a) of claim 1 followed by other limitations of the sgRNAs in step b) of claim 1 makes the claim confusing. Put everything related to the structure/function of the sgRNAs together in one step.
The phrase “obtaining purified Cas9mRNA, purified Ptgds-sgRNA1, and purified Ptgds-sgRNA2 by in vitro transcription” in step b) of claim 1 is possibly two different steps, i.e. “providing purified mRNA encoding Cas9” and “purifying the sgRNAs obtained in step a)”.
Steps a) and b) of claim 1 never require introducing the two sgRNAs into any cell or animal.
Steps a)-d) of claim 1 can be combined and written more succinctly as ---introducing: i) mRNA encoding Cas9; ii) a single guide RNA (sgRNA) comprising the nucleic acid sequence of SEQ ID NO: 1; and iii) an sgRNA comprising the nucleic acid sequence of SEQ ID NO: 3 into a rat embryo such that an endogenous Ptgds gene is inactivated in germ cells of the embryo---
The phrase “knocking out a 2,944 bp sequence fragment in the rat Ptgds gene using a CRISPR/Cas9 system to obtain an inactivated Ptgds gene” in step c) of claim 1 does not make sense because the “CRISPR/Cas9 system” does not refer to the mRNA encoding Cas9 or the two sgRNAs in steps a) and b). There are no rat cells or rat DNA present in step c), so there is nothing to “knock out”. This step is also out of order with step 4) which DOES require injecting mRNA encoding Cas9 and the two sgRNAs into a rat embryo. If this step is intended to create a donor sequence for integration into an endogenous rat PTGDS gene, then much clarification is required.
The phrase “d) injecting the purified mRNA encoding Cas9, the purified Ptgds-sgRNA1, the purified Ptgds-sgRNA2, and the inactivated Ptgds gene into rat embryos, and e) transplanting the embryos into fallopian tubes of surrogate recipient rats to obtain neonatal rats” in claim 1 is unclear because it appears to infer a donor sequence with an inactivated PTGDS gene is injected into the rat embryo, but step a-c) never results in a donor sequence with an inactivated PTGDS gene.
The final product in step f) (“obtaining the offspring rats of the surrogate recipient rats as neonatal rats”) is unclear because the phrase does not result in a genetically modified rat whose genome comprise an inactivated PTGDS gene.
The phrase “identifying neonatal rats with a heterozygous inactivated PTGDS gene” in step g) of claim 1 is unclear because the phrase does not result in identifying a genetically modified rat whose genome comprise an inactivated PTGDS gene.
The term “inactived” in steps g) and h) in claim 1 should be ---inactivated---.
The phrase “h) conducting breeding on the neonatal rats with a heterozygous inactivated PTGDS gene with wild-type rats for multiple generations, and identifying offspring rats obtained from each generation until obtaining homozygous rats, the obtained homozygous rats are Ptgds gene knockout rat model” in step h) claim 1 is confusing because it is actually at least two steps and because it does not have a nexus with the preamble. The preamble requires making PTGDS knockout rats which seems to have already occurred in step h). Breeding the rats to obtain more genetically modified rats that have increased susceptibility to kidney yin deficiency in step h) is beyond what is in the preamble. There also seems to be some inference that the rats in step h) may be limited to rats with a heterozygous inactivated PTGDS which is missing from the final lines. If the point of step h) is to make homozygous rats from heterozygous rats, then step h) need clarified. Regardless, step h) should also result in obtaining a genetically modified rat whose genome comprises an inactivated PTGDS gene. Finally, step h) does not make sense because the meaning of “kidney yin deficiency” in the last two lines of claim 1 makes the claim unclear. It is unclear how the term “yin” further limits the type of kidney deficiency or when they have “increased susceptibility” without having “kidney yin deficiency” (see 112/2nd).
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 112
Enablement
Claims 1, 3, 5-8 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 genetically modified rat whose genome comprises an inactivated prostaglandin-H gene, wherein the rat has a kidney deficiency, does not reasonably provide enablement for claim 1 as 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.
Withdrawn rejections
The rejection regarding modifying an endogenous PTGDS “locus” in claim 1 has been withdrawn in view of the amendment.
The rejection regarding knocking out “a 2944 bp sequence” as specifically required in step 3 of claim 1 using any “sgRNA1” and “sgRNA2” as broadly encompassed by step 1 of claim 1 other than SEQ ID NO: 1 and 3 has been withdrawn in view of the amendment.
Pending rejections
A) The specification does not enable making/using any knockout rat with “increased susceptibility to kidney yin deficiency as compared to wild-type rats” as broadly encompassed by claim 1 other than a genetically modified rat whose genome comprises an inactivated PTGDS gene, wherein the rat has a kidney deficiency.
Claim 1 is drawn to A method for constructing a prostaglandin D2 synthase (Prgds gene knockout rat model, comprising the following steps:
a) designing two different sgRNAs, Ptgds-sgRNA1 and Ptgds-sgRNA2, wherein the two different sgRNAs target two different sequences of a rat Ptgds gene;
b) providing purified mRNA encoding Cas9mRNA, purified Ptgds-sgRNA1, and purified Ptgds-sgRNA2, wherein the Ptgds-sgRNA1 has a nucleotide sequence set forth in SEQ ID NO: 1; and the Ptgds-sgRNA2 has a nucleotide sequence set forth in SEQ ID NO: 3;
c) knocking out a 2,944 bp sequence fragment in the rat Ptgds gene using a CRISPR/Cas9 system to obtain an inactivated Ptgds gene;
d) injecting the purified mRNA encoding Cas9mRNA, the purified Ptgds-sgRNA1, the purified Ptgds-sgRNA2, and the inactivated Ptgds knockout gene into rat embryos,
e) transplanting the embryos into fallopian tubes of surrogate recipient rats;
f) obtaining the offspring rats of the surrogate recipient rats as neonatal rats;
g) identifying the neonatal rats with a heterozygous inactived Ptgds gene; and
h) conducting breeding on the neonatal rats with a heterozygous [inactivated] Ptgds gene with wild-type rats for multiple generations, and identifying offspring rats obtained from each generation to gene identification until obtaining homozygous rats, the obtained homozygous rats are Ptgds gene knockout rat model with increased susceptibility to kidney yin deficiency as compared to wild-type rats.
A GenBank search using SEQ ID NO: 11 says the sequence is in a rat prostaglandin H-2 D-isomerase gene which is a synonym for prostaglandin 2D synthase gene. See “Claim Confusion” above.
CN111647628 taught a rat whose genome comprises an inactivated CES2 gene and a method of making it by
i) identifying CRISPR target sequences in a rat CES2 gene,
ii) making two sgRNAs that binds two different CES2 target sequences;
iii) administering a vector encoding Cas9 and the sgRNAs to a rat embryo such that the CES2 gene is inactivated in the embryo;
iv) transplanting the embryo into recipient females such that a genetically modified rat whose genomes comprise an inactivated CES2 gene are obtained, wherein the offspring rats have increased susceptibility to kidney deficiency as compared to wild-type rats (claim 1).
Eguchi (PNAS, 1999, Vol. 96, pg 726-730) created a targeting vector encoding a mutant PGDS gene (exons 2-5 replaced with a Neo marker gene), transfecting mouse ES cells with the vector, identifying ES cells with an inactivated PTGDS gene, using the ES cells to make chimeric males that were bred to C57BL6 females to obtain heterozygous mice, interbreeding the mice to obtain a mouse whose genome comprised a homozygous inactivated PGDS gene (pg 727, col. 1, lines 1-10; pg 727, col. 2, 1st full para).
The specification is limited to making a rat whose genome comprises an inactivated PTGDS gene and a method of making it by
i) introducing two sgRNAs that binds the two different CES2 target sequences and mRNA encoding Cas9 into a rat embryo such that the PTGDS gene is inactivated in the embryo;
ii) transplanting the embryo into recipient females such that a genetically modified rat whose genomes comprise an inactivated PTGDS gene are obtained, wherein the offspring rats have increased susceptibility to kidney deficiency as compared to wild-type rats (Examples).
The specification does not correlate
i) identifying CRISPR target sequences in a rat PTGDS gene,
ii) making two sgRNAs that binds two different PTGDS target sequences;
iii) administering a vector encoding Cas9 and the sgRNAs to a rat embryo such that the PTGDS gene is inactivated in the embryo;
iv) transplanting the embryo into recipient females such that a genetically modified rat whose genomes comprise an inactivated PTGDS gene are obtained, wherein the offspring rats have increased susceptibility to kidney deficiency as compared to wild-type rats as described in the specification and the steps in CN111647628 to the steps as broadly encompassed by claim 1.
B) The specification does not enable injecting mRNA encoding Cas9 and the sgRNA1 and sgRNA2 into rat embryos, transplanting the embryos into recipient females, and “obtaining the offspring rats of the surrogate recipient rats as neonatal rats” as required in step f) of claim 1 without obtaining a rat whose genome has a heterozygous inactivated PTGDS gene. The rats are bred in step h) without clearly obtaining homozygous rats whose genomes comprise a homozygous disruption in a PTGDS gene. Each rat must be genetically modified and have at least one inactivated PTGDS allele.
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 perform the method of claim 1 as broadly written.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Written Description
Claims 1, 3, 5-8 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.
Withdrawn rejections
The rejection regarding modifying an endogenous PTGDS “locus” in claim 1 has been withdrawn in view of the amendment.
The rejection regarding knocking out “a 2944 bp sequence” as specifically required in step 3 of claim 1 using any “sgRNA1” and “sgRNA2” as broadly encompassed by step 1 of claim 1 other than SEQ ID NO: 1 and 3 has been withdrawn in view of the amendment.
Pending rejections
A) The specification lacks written description for any knockout rat with “increased susceptibility to kidney yin deficiency as compared to wild-type rats” as broadly encompassed by claim 1 other than a genetically modified rat whose genome comprises an inactivated PTGDS gene, wherein the rat has a kidney deficiency.
Claim 1 is recited above.
A GenBank search using SEQ ID NO: 11 says the sequence is in a rat prostaglandin H-2 D-isomerase gene which is a synonym for prostaglandin 2D synthase gene. See “Claim Confusion” above.
CN111647628 taught a rat whose genome comprises an inactivated CES2 gene and a method of making it by
i) identifying CRISPR target sequences in a rat CES2 gene,
ii) making two sgRNAs that binds two different CES2 target sequences;
iii) administering a vector encoding Cas9 and the sgRNAs to a rat embryo such that the CES2 gene is inactivated in the embryo;
iv) transplanting the embryo into recipient females such that a genetically modified rat whose genomes comprise an inactivated CES2 gene are obtained, wherein the offspring rats have increased susceptibility to kidney deficiency as compared to wild-type rats (claim 1).
Eguchi (PNAS, 1999, Vol. 96, pg 726-730) created a targeting vector encoding a mutant PGDS gene (exons 2-5 replaced with a Neo marker gene), transfecting mouse ES cells with the vector, identifying ES cells with an inactivated PTGDS gene, using the ES cells to make chimeric males that were bred to C57BL6 females to obtain heterozygous mice, interbreeding the mice to obtain a mouse whose genome comprised a homozygous inactivated PGDS gene (pg 727, col. 1, lines 1-10; pg 727, col. 2, 1st full para).
The specification is limited to making a rat whose genome comprises an inactivated PTGDS gene and a method of making it by
i) introducing two sgRNAs that binds the two different CES2 target sequences and mRNA encoding Cas9 into a rat embryo such that the PTGDS gene is inactivated in the embryo;
ii) transplanting the embryo into recipient females such that a genetically modified rat whose genomes comprise an inactivated PTGDS gene are obtained, wherein the offspring rats have increased susceptibility to kidney deficiency as compared to wild-type rats (Examples).
The specification does not correlate
i) identifying CRISPR target sequences in a rat PTGDS gene,
ii) making two sgRNAs that binds two different PTGDS target sequences;
iii) administering a vector encoding Cas9 and the sgRNAs to a rat embryo such that the PTGDS gene is inactivated in the embryo;
iv) transplanting the embryo into recipient females such that a genetically modified rat whose genomes comprise an inactivated PTGDS gene are obtained, wherein the offspring rats have increased susceptibility to kidney deficiency as compared to wild-type rats as described in the specification and the steps in CN111647628 to the steps as broadly encompassed by claim 1.
B) The specification lacks written description for injecting mRNA encoding Cas9 and the sgRNA1 and sgRNA2 into rat embryos, transplanting the embryos into recipient females, and “obtaining the offspring rats of the surrogate recipient rats as neonatal rats” as required in step f) of claim 1 without obtaining a rat whose genome has a heterozygous inactivated PTGDS gene. The rats are bred in step h) without clearly obtaining homozygous rats whose genomes comprise a homozygous disruption in a PTGDS gene. Each rat must be genetically modified and have at least one inactivated PTGDS allele. Accordingly, the concept lacks written description.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Indefiniteness
Claims 1, 3, 5-8 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.
A) The term “yin” in claim 1 makes the phrase “kidney yin deficiency” in claim 1 indefinite. It is unclear whether it encompasses any kidney deficiency or not. If the phrase limits the type of kidney deficiency, then it is unclear how or what types of kidney deficiencies are being excluded/included. Therefore, those of skill would not be able to determine when they were infringing on the claim.
Response to arguments
Applicants argue the phrase “kidney yin deficiency” was well-known as described by references 4 and 5. Applicants’ argument is not persuasive. The references do not define the phrase. It is unclear whether it encompasses any kidney deficiency or not. If the phrase limits the type of kidney deficiency, then it is unclear how or what types of kidney deficiencies are being excluded/included. Therefore, those of skill would not be able to determine when they were infringing on the claim.
B) The phrase “designing two different sgRNAs, PTGDS-sgRNA1 and PTGDS-sgRNA2, wherein the two different sgRNAs target two different sequences of a rat PTGDS gene” in claim 1 is indefinite. It is unclear whether “PTGDS-sgRNA1 and PTGDS-sgRNA2” are just generic names for the two sgRNAs or if they carry any weight regarding the structure or function. The phrase reads as parenthetical, so it is also unclear whether the parenthetical thought is optional or whether the sgRNAs MUST be named PTGDS-sgRNA1 and PTGDS-sgRNA2. Therefore, it is unclear whether those of skill who decide to name the two sgRNAs something other than PTGDS-sgRNA1 and PTGDS-sgRNA2 would be infringing on the claim.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
C) It is unclear whether the phrase “providing purified mRNA encoding Cas9, purified Ptgds-sgRNA1, and purified Ptgds-sgRNA2” in claim 1 is one step, i.e. “providing purified mRNA encoding Cas9, providing purified sgRNA comprising the nucleic acid sequence of SEQ ID NO: 1, and providing purified sgRNA comprising the nucleic acid sequence of SEQ ID NO: 3”, or if it is two different steps, i.e. “providing purified mRNA encoding Cas9, and c) purifying the sgRNA comprising the nucleic acid sequence of SEQ ID NO: 1 and the sgRNA comprising the nucleic acid sequence of SEQ ID NO: 3 provided in step b)”.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
D) The phrase “knocking out a 2,944 bp sequence fragment in the rat Ptgds gene using a CRISPR/Cas9 system to obtain an inactivated Ptgds gene” in step c) of claim 1 makes the claim indefinite. The “CRISPR/Cas9 system” does not refer to the mRNA encoding Cas9 or the two sgRNAs in step a) or b). There are no rat cells or rat DNA present in step a-c), so there is nothing to “knockout”. This step is also out of order with step d) which DOES require injecting mRNA encoding Cas9 and the two sgRNAs into a rat embryo. If this step is intended to create a donor sequence for integration into an endogenous rat PTGDS gene, then that concept is missing from the step.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
E) The phrase “injecting the purified mRNA encoding Cas9, the purified Ptgds-sgRNA1, the purified Ptgds-sgRNA2, and the inactivated Ptgds knockout gene into rat embryos, e) transplanting the embryos into fallopian tubes of surrogate recipient rats to obtain neonatal rats” in step d-e) of claim 1 makes the claim indefinite. It appears to infer a donor sequence with an inactivated PTGDS gene is injected into the rat embryo, but the steps never results in a donor sequence capable of inactivating a PTGDS gene.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
F) The phrase “obtaining the offspring rats of the surrogate recipient rats as neonatal rats” in step f) of claim 1 makes the claim indefinite because the phrase does not result in a genetically modified rat whose genome comprise an inactivated PTGDS gene from the rat embryos transplanted into the fallopian tubes of recipient rats in step e).
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
G) The phrase “conducting breeding on the neonatal rats with a heterozygous inactived [sic] with wild-type rats for multiple generations, and identifying offspring rats obtained from each generation until obtaining homozygous rats, the obtained homozygous rats are Ptgds gene knockout rat model” in claim 1 makes the claim indefinite because it does not have a nexus with the preamble. The preamble requires making PTGDS knockout rats which seems to have already occurred in step g) and h). Breeding the rats to obtain more genetically modified rats in step h) is beyond what is in the preamble. There also seems to be some inference that the rats in step g) and h) may be limited to rats with a homozygous inactivated PTGDS gene which is missing from step h). Finally, “rat model with increased susceptibility to kidney yin deficiency” step h) does not have a nexus with simply making a PTGDS gene knockout rat in the preamble. Waiting to determine whether the rat has increased susceptibility to “kidney yin deficiency” as in step h) is beyond what occurs in the preamble.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
I) Claim 8 remains indefinite because the logic, reagents, breeding schedule, and resultant rats obtained in each step of claim 8 do not make sense or have a nexus with claim 1. The products, reagents, and labeling of the offspring required to arrive at a rat whose genome comprises a homozygous disruption in a PTGDS gene cannot be determined.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 103
Claims 1, 3, 5-8 are rejected under 35 U.S.C. 103 as being unpatentable over CN111647628 in view of Eguchi (PNAS, 1999, Vol. 96, pg 726-730), M94134 Igarashi (PNAS, 1992, Vol. 89, No. 12, pg 5376-5380), and Li (Oncotarget, 2018, Vol. 9, No. 41, pg 26586-26602).
CN111647628 taught a rat whose genome comprises an inactivated CES2 gene and a method of making it by
i) identifying CRISPR target sequences in a rat CES2 gene,
ii) making two sgRNAs that binds two different CES2 target sequences;
iii) administering a vector encoding Cas9 and the sgRNAs to a rat embryo such that the CES2 gene is inactivated in the embryo;
iv) transplanting the embryo into recipient females such that a genetically modified rat whose genomes comprise an inactivated CES2 gene are obtained, wherein the offspring rats have increased susceptibility to kidney deficiency as compared to wild-type rats (claim 1).
‘628 did not teach inactivating the PTGDS gene as required in claim 1.
However, Eguchi (PNAS, 1999, Vol. 96, pg 726-730) created a targeting vector encoding a mutant PGDS gene (exons 2-5 replaced with a Neo marker gene), transfecting mouse ES cells with the vector, identifying ES cells with an inactivated PTGDS gene, using the ES cells to make chimeric males that were bred to C57BL6 females to obtain heterozygous mice, interbreeding the mice to obtain a mouse whose genome comprised a homozygous inactivated PGDS gene (pg 727, col. 1, lines 1-10; pg 727, col. 2, 1st full para).
The genomic sequence of the rat PTGDS gene was described by M94134 (see homology with SEQ ID NO: 1 and 3 above).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make a rodent with an inactivated gene using two sgRNAs and mRNA encoding Cas9 as described by ‘628 in a PTGDS gene as described by Eguchi and Igarashi. Those of ordinary skill in the art at the time of filing would have been motivated to disrupt the PTGDS gene in a rat to obtain larger kidneys for research purposes.
The limitation of 2944 bp sequence being deleted in claim 1 has been included because the genomic sequence of the rat PTGDS gene was described by M94134, and SEQ ID NO: 1 and 3 above cause a 2944 bp deletion as claimed.
Claim 1 has been included because the genomic sequence of the rat PTGDS gene was described by M94134 (see homology with SEQ ID NO: 1 and 3 above).
The concept of the rat having “increased susceptibility to kidney yin deficiency” in claim 1 has been included because CN111647628 taught the limitation of “increased susceptibility to kidney deficiency”, because the metes and bounds are unclear, and because Li taught prostaglandins and their synthases were known to be involved with kidney disease (see title; pg 26592, col. 2, “PGD2 in kidney disease”, specifically the discussion of prostaglandin D synthase “PGDS”).
Claim 3 has been included because the sequence between SEQ ID NO: 1 and 3 has an intron and an exon.
The concept of how to identify rats of interest in claim 5-7 are well-within the purview of the ordinary artisan at the time of filing.
The breeding strategy of claim 8 is obvious in view of the teachings of ‘628 and Eguchi.
Response to arguments
Applicants argue the references fail to teach all the limitations claimed. Applicants’ argument is not persuasive for reasons set forth above.
Applicants argue the references do not teach rats with increased susceptibility to kidney yin deficiency. Applicants’ argument is not persuasive. The concept of the rat having “increased susceptibility to kidney yin deficiency” in claim 1 has been included because CN111647628 taught the limitation of “increased susceptibility to kidney deficiency”, because the metes and bounds are unclear, and because Li taught prostaglandins and their synthases were known to be involved with kidney disease (see title; pg 26592, col. 2, “PGD2 in kidney disease”, specifically the discussion of prostaglandin D synthase “PGDS”).
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.
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