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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8-27-26 has been entered.
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 Claims 9-11, 14-16 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 8-27-26 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/interpretation
It is assumed the term DsRed2 in claim 1 was well-known in the art.
The nucleic acid sequence in item ii) of claim 1 can be written more simply 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---.
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.
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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If applicants are attempting to indicate the nucleic acid encoding DsRed2, GFP, kanaR, or NeoR is capable of being expressed under the control of the promoter but TSHR is not, then that concept is missing from the claim.
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.
If applicants are attempting to indicate the nucleic acid encoding DsRed2, GFP, kanaR, or NeoR is excised after recombination, then that concept is missing from the claim.
The meaning of 250-750U of a TAT-Cre recombinase fusion protein in claim 1 cannot be determined. The specification and the art at the time of filing do not teach the structure/function of TAT-Cre recombinase fusion protein or when an amount of the fusion protein is “250-750U” as claimed. 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”.
Accordingly, claim 1 lacks written description as claimed.
Response to arguments
Applicants point to Fig. 1 and 2A and somehow conclude claim 1 captures every element of the figures. Applicants’ argument is not persuasive. Claim 1 is so blurry in its original form and in the form provided on 8-27-26 that the structures cannot be discerned. Furthermore, there is no function in the claim saying the nucleic acid encoding DsRed2, GFP, kanaR, or NeoR is capable of being expressed under the control of the promoter but TSHR is not. There is nothing in the claim that says the nucleic acid is capable of expressing TSHR but not DsRed2, GFP, kanaR, or NeoR after recombination. There is nothing in the claim that says the nucleic acid encoding DsRed2, GFP, kanaR, or NeoR is excised after recombination, then that concept is missing from the claim. There is nothing in the claim about the nucleic acid sequence having homology arms that make the sequence capable of integration into a Rosa26 gene.
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 specification does not enable using the nucleic acid as broadly encompassed by claim 1 without the nucleic acid encoding DsRed2, GFP, kanaR, or NeoR being capable of being expressed under the control of the promoter. It is not capable of expressing TSHR until recombination occurs.
The specification does not enable using the nucleic acid as broadly encompassed by claim 1 without the nucleic acid being capable of expressing TSHR but not DsRed2, GFP, kanaR, or NeoR after recombination.
The specification does not enable using the nucleic acid as broadly encompassed by claim 1 without the nucleic acid encoding DsRed2, GFP, kanaR, or NeoR being capable of being excised during recombination.
The meaning of 250-750U of a TAT-Cre recombinase fusion protein in claim 1 cannot be determined. The specification and the art at the time of filing do not teach the structure/function of TAT-Cre recombinase fusion protein or when an amount of the fusion protein is “250-750U” as claimed. 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”.
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.
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 meaning of 250-750U of a TAT-Cre recombinase fusion protein in claim 1 cannot be determined. The specification and the art at the time of filing do not teach the structure/function of TAT-Cre recombinase fusion protein or when an amount of the fusion protein is “250-750U” as claimed. 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”.
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) was 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.
The art at the time of filing did not reasonably teach or suggest a nucleic acid sequence comprising from 5’ to 3’: a promoter, a nucleic acid sequence encoding DsRed2, GFP, KanaR, or NeoR in reverse orientation flanked on both sides by loxP sites, and a nucleic acid sequence encoding TSHR or combining it with a TAT-Cre fusion protein.
Conclusion
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
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