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 3-8, 12, 13 have been canceled. Claims 1, 2, 9-11, 14-16 remain pending.
Election/Restrictions
Applicants elected Group I, claims 1, 2, 6, without traverse in the reply filed on 11-24-25. Claims 9-11, 14-16 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicants elected the species of “thyroid antigens”; however, the only “thyroid antigen” described by applicants that is an “autoantigen” as required in claim 1 is “thyroid stimulating hormone receptor” (TSHR) (claim 6; pg 2, lines 1-5; pg 8, lines 1-5).
Claims 1 and 2 are under consideration as they relate to TSHR as the autoantigen.
Applicant's arguments filed 3-16-26 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.
Claim objections
The phrase “for preparing an animal in which an autoimmune response disease is induced” in claim 1 is an intended use and bears no patentable weight on the structure or function of the kit.
It is unclear whether the phrase “red fluorescent protein DsRed2” in claim 1 is limited to DsRed2 or if it encompasses any RFP including DsRed2. Perhaps the abbreviation DsRed2 is adequate if it was well-known in the art what it means.
The Markush Group in claim 1 is a mixed bag of proteins and genes, but it should be limited to proteins, i.e. “a protein selected from the group consisting of…”.
The nucleic acid sequence in item ii) of claim 1 can be written more clearly as ---a nucleic acid sequence encoding DsRed2, green fluorescence protein, kanamycin resistance protein, or neomycin resistance protein in reverse orientation flanked on both sides by loxP sites---.
The capability of the nucleic acid sequence encoding TSHR being operably linked to the promoter after Cre-recombination in claim 1 is unclear.
The meaning of 250-750U of TAT-Cre recombinase in claim 1 cannot be determined.
The configuration of the TAT-Cre recombinase “to be administered to the animal after the isolated nucleic acid is introduced into the animal” makes no sense because this is a product claim. The intended use has no bearing on the structure or function of the TAT-Cre recombinase.
Claim Rejections - 35 USC § 112
Written Description
Claims 1, 2 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 using any regulatory sequence in item a) of claim 1 has been withdrawn because item a) has been limited to a promoter.
The rejection regarding any thyroid protein that is an autoantigen as broadly encompassed by claim 1 has been withdrawn because claim 1 has been limited to TSHR.
Pending rejections
The specification lacks written description for the isolated nucleic acid molecule of claim 1 other than one comprising from 5’ to 3’: a) a promoter; b) a nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR in reverse orientation flanked by a pair of loxP sites; c) a nucleic acid sequence encoding thyroid stimulation hormone receptor (TSHR). Expression of TSHR is blocked in the molecule because of the sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites. Upon removal of the loxP cassette by recombinase, the molecule has the TSHR coding sequence operably linked to the promoter and allows expression of TSHR.
Claim 1 is drawn to
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The claim says the nucleotide encoding TSHR is not operably linked to the promoter or expressed prior to Cre-mediated recombination, but the claim is drawn to a kit. It is not a method that involves Cre-mediated recombination. The claim does not require expression of DsRed2, GFP, kanaR, or NeoR or TSHR.
If applicants are attempting to indicate the nucleic acid in item b) of claim 1 AS IS is capable of expressing DsRed2, GFP, kanaR, or NeoR but not TSHR, then that concept is missing from the claim. However, it is unclear how the nucleic acid in item b) could express DsRed2, GFP, kanaR, or NeoR because it is in reverse orientation and not operably linked to a promoter in that direction. When a recombinase removes the nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites, the TSHR coding sequence becomes operably linked to the promoter and expression of TSHR may occur; however, this capability is missing from the claims.
If applicants are attempting to indicate the nucleic acid is capable of expressing TSHR but not DsRed2, GFP, kanaR, or NeoR after recombination, then that concept is missing from the claim.
The specification fails to correlate a molecule in which the TSHR coding sequence becomes operably linked to the promoter and capable of expressing TSHR upon removal of the nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites to any nucleic acid molecule as broadly claimed.
The meaning of 250-750U of TAT-Cre recombinase in claim 1 cannot be determined. It is unclear when Cre recombinase is “TAT-Cre recombinase”. If applicants are attempting to refer to a fusion protein comprising TAT and Cre-recombinase, then that should be clearly set forth. The specification and the art at the time of filing do not teach the structure of 250-750U of TAT-Cre recombinase. If “U” refers to units, then the metes and bounds of how much fusion protein is in one unit. While a TAT-Cre fusion protein may have a molecular weight in mg/ml, it is unclear how much is in a “unit”.
The configuration of the TAT-Cre recombinase “to be administered to the animal after the isolated nucleic acid is introduced into the animal” is an intended use has no bearing on the structure or function of the TAT-Cre recombinase. In particular, the “configuration” of TAT-Cre for use “after the isolated nucleic acid is introduced into” an animal is different that the “configuration” of TAT-Cre for use before “the isolated nucleic acid is introduced into” an animal.
The specification lacks written description for a kit “for preparing an animal in which an autoimmune response disease is induced” in claim 1. The specification fails to teach how to use the kit to induce an autoimmune disease in any animal. The concept encompasses inducing an autoimmune disease in a human which is not contemplated or disclosed. The concept encompasses inducing an autoimmune disease in non-human lab animals, but the specification fails to teach how to express TSHR or DsRed2, GFP, kanaR, or NeoR such that an autoimmune disease is induced in non-human lab animals.
Applicants are reminded that if a nucleic acid molecule comprising a) a promoter; b) a nucleic acid sequence encoding a marker protein in reverse orientation flanked by a pair of loxP sites; c) a nucleic acid sequence encoding a protein of interest was known in the art, then it is incumbent upon applicants to disclose such a reference.
Accordingly, claim 1 lacks written description as claimed.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Enablement
Claims 1, 2 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 comprising from 5’ to 3’: a) a promoter; b) a nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR in reverse orientation flanked by a pair of loxP sites; c) a nucleic acid sequence encoding thyroid stimulation hormone receptor (TSHR). Expression of TSHR is blocked in the molecule because of the sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites. Upon removal of the loxP cassette by recombinase, the molecule has the TSHR coding sequence operably linked to the promoter and allows expression of TSHR.
The specification does not reasonably provide enablement for the nucleic acid molecule of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
The specification does not enable making/using any isolated nucleic acid molecule of claim 1 other than one comprising from 5’ to 3’: a) a promoter; b) a nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR in reverse orientation flanked by a pair of loxP sites; c) a nucleic acid sequence encoding thyroid stimulation hormone receptor (TSHR). Expression of TSHR is blocked in the molecule because of the sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites. Upon removal of the loxP cassette by recombinase, the molecule has the TSHR coding sequence operably linked to the promoter and allows expression of TSHR.
Claim 1 is recited above.
The claim says the nucleotide encoding TSHR is not operably linked to the promoter or expressed prior to Cre-mediated recombination, but the claim is drawn to a kit. It is not a method that involves Cre-mediated recombination. The claim does not require expression of DsRed2, GFP, kanaR, or NeoR or TSHR.
If applicants are attempting to indicate the nucleic acid in item b) of claim 1 AS IS is capable of expressing DsRed2, GFP, kanaR, or NeoR but not TSHR, then that concept is missing from the claim. However, it is unclear how the nucleic acid in item b) could express DsRed2, GFP, kanaR, or NeoR because it is in reverse orientation and not operably linked to a promoter in that direction. When a recombinase removes the nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites, the TSHR coding sequence becomes operably linked to the promoter and expression of TSHR may occur; however, this capability is missing from the claims.
If applicants are attempting to indicate the nucleic acid is capable of expressing TSHR but not DsRed2, GFP, kanaR, or NeoR after recombination, then that concept is missing from the claim.
The specification fails to correlate a molecule in which the TSHR coding sequence becomes operably linked to the promoter and capable of expressing TSHR upon removal of the nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites to any nucleic acid molecule as broadly claimed.
The meaning of 250-750U of TAT-Cre recombinase in claim 1 cannot be determined. It is unclear when Cre recombinase is “TAT-Cre recombinase”. If applicants are attempting to refer to a fusion protein comprising TAT and Cre-recombinase, then that should be clearly set forth. The specification and the art at the time of filing do not teach the structure of 250-750U of TAT-Cre recombinase. If “U” refers to units, then the metes and bounds of how much fusion protein is in one unit. While a TAT-Cre fusion protein may have a molecular weight in mg/ml, it is unclear how much is in a “unit”.
The configuration of the TAT-Cre recombinase “to be administered to the animal after the isolated nucleic acid is introduced into the animal” is an intended use has no bearing on the structure or function of the TAT-Cre recombinase. In particular, the “configuration” of TAT-Cre for use “after the isolated nucleic acid is introduced into” an animal is different that the “configuration” of TAT-Cre for use before “the isolated nucleic acid is introduced into” an animal.
The specification does not enable making/using a kit “for preparing an animal in which an autoimmune response disease is induced” in claim 1. The specification fails to teach how to use the kit to induce an autoimmune disease in any animal. The concept encompasses inducing an autoimmune disease in a human which is not contemplated or disclosed. The concept encompasses inducing an autoimmune disease in non-human lab animals, but the specification fails to teach how to express TSHR or DsRed2, GFP, kanaR, or NeoR such that an autoimmune disease is induced in non-human lab animals.
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 any nucleic acid molecule as broadly encompassed by claim 1 other than one comprising from 5’ to 3’: a) a promoter; b) a nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR in reverse orientation flanked by a pair of loxP sites; c) a nucleic acid sequence encoding TSHR having the functions discussed above.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above. Applicants are reminded that if a nucleic acid molecule comprising a) a promoter; b) a nucleic acid sequence encoding a marker protein in reverse orientation flanked by a pair of loxP sites; c) a nucleic acid sequence encoding a protein of interest was known in the art, then it is incumbent upon applicants to disclose such a reference.
Indefiniteness
Claims 1, 2 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.
The functions of the elements in claim 1 cannot be determined. Claim 1 says the nucleotide encoding TSHR is not operably linked to the promoter or expressed prior to Cre-mediated recombination, but the claim is drawn to a kit. It is not a method that involves Cre-mediated recombination. The claim does not require expression of DsRed2, GFP, kanaR, or NeoR or TSHR.
If applicants are attempting to indicate the nucleic acid in item b) of claim 1 AS IS is capable of expressing DsRed2, GFP, kanaR, or NeoR but not TSHR, then that concept is missing from the claim. However, it is unclear how the nucleic acid in item b) could express DsRed2, GFP, kanaR, or NeoR because it is in reverse orientation and not operably linked to a promoter in that direction. When a recombinase removes the nucleic acid sequence encoding DsRed2, GFP, kanaR, or NeoR flanked by loxP sites, the TSHR coding sequence becomes operably linked to the promoter and expression of TSHR may occur; however, this capability is missing from the claims.
If applicants are attempting to indicate the nucleic acid is capable of expressing TSHR but not DsRed2, GFP, kanaR, or NeoR after recombination, then that concept is missing from the claim.
The meaning of 250-750U of TAT-Cre recombinase in claim 1 cannot be determined. It is unclear when Cre recombinase is “TAT-Cre recombinase”. If applicants are attempting to refer to a fusion protein comprising TAT and Cre-recombinase, then that should be clearly set forth. The specification and the art at the time of filing do not teach the structure of 250-750U of TAT-Cre recombinase. If “U” refers to units, then the metes and bounds of how much fusion protein is in one unit. While a TAT-Cre fusion protein may have a molecular weight in mg/ml, it is unclear how much is in a “unit”.
It is unclear how the “configuration” of the TAT-Cre recombinase “to be administered to the animal after the isolated nucleic acid is introduced into the animal” bears patentable weight on the structure or function of the TAT-Cre recombinase. In particular, the “configuration” of TAT-Cre for use “after the isolated nucleic acid is introduced into” an animal is different that the “configuration” of TAT-Cre for use before “the isolated nucleic acid is introduced into” an animal.
The metes and bounds of a kit “for preparing an animal in which an autoimmune response disease is induced” in claim 1. The specification fails to teach how to use the kit to induce an autoimmune disease in any animal. The concept encompasses inducing an autoimmune disease in a human which is not contemplated or disclosed. The concept encompasses inducing an autoimmune disease in non-human lab animals, but the specification fails to teach how to express TSHR or DsRed2, GFP, kanaR, or NeoR such that an autoimmune disease is induced in non-human lab animals. Accordingly, those of skill would not be able to determine what structures are associated with a kit having that function.
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
The rejection of claims 1, 2 under 35 U.S.C. 103 as being unpatentable over Hasegawa (Exp. Anim., 2013, Vol. 62, No. 4, pg 295-304) in view of Nagayama (Biochemical and Biophysical Research Communications, 1989, Vol.165, No.3, pg 1184-1190), Libert (Biochemical and Biophysical Research Communications, 1989, Vol.165, No.3, pg 1250-1255), Wadsworth (Science, 1990, Vol.249, pg 1349-1472), and Graves (The J. Clin. Endocrinology & Metabolism, 1999, Vol.84, No.6, pg 2177-2181) has been withdrawn.
Hasegawa taught an isolated nucleic acid molecule comprising from 5’ to 3’: a) a promoter; b) a nucleic acid sequence encoding GFP flanked by a pair of loxP sites; c) a nucleic acid sequence encoding tdsRed. Hasegawa did not teach the sequence encoding GFP was in reverse orientation relative to the promoter as required in claim 1. Claim 1 as written never requires the nucleic acid sequence is capable of expressing DsRed2, GFP, kanaR, neoR or any other marker protein when it is in reverse orientation and flanked by loxP sites. The nucleic acid in claim 1 is incapable of expressing DsRed2, GFP, kanaR, neoR or any other marker protein in reverse orientation flanked by loxP sites before recombination because it does not have a promoter. The nucleic acid in claim 1 is incapable of expressing DsRed2, GFP, kanaR, neoR or any other marker protein in reverse orientation flanked by loxP sites AFTER recombination because it has been deleted.
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