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 .
Status of the Claims
Claims 1-2, 5, 7, 16-17, 21, 26, 30, 33-36, 40, 44, 49-50, 54, 61, 63, and 85 are pending.
Claim Rejections - 35 USC § 112
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.
Claim 49 is 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 49 recites the limitation "the rAAV5 vector". There is insufficient antecedent basis for this limitation in the claim. For purposes of examination, this will be interpreted as “the vector” of claim 1.
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.
Bougneres
Claims 1-2, 5, 7, 16-17, 21, 26, 30, 33-36, 40, 44, 49-50, 54, 61, 63, and 85 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bougneres (WO2019143803A1) (Published 25 July 2019).
Regarding claim 1, Bougneres teaches a method of expressing 21 -hydroxylase (21 OH) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a rAAV particle comprising a rAAV vector comprising a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleotide sequence encoding a 21 -hydroxylase (21 OH) protein, the non-AAV nucleotide sequence operably linked to a promote. (Bougneres [0015]). Bougneres teaches that in some embodiments, rAAV vectors or rAAV particles comprising a nucleic acid sequence encoding 21 OH are administered to a subject at a dose ranging from about 1011 to about 1014 vg/kg body weight of the subject.
(Bougneres [00144]).
Regarding claim 2, Bougneres teaches that their method may be used to treat a subject with 21 -hydroxylase deficiency (Bougneres [00123, 00125, claim 22]).
Regarding claim 5, Bougneres teaches that their method may be used to treat a subject that is affected with congenital adrenal hyperplasia (CAH). (Bougneres [0018]).
Regarding claim 7, Bougneres teaches that their method may result in transgene expression of 21OH in the adrenal cortex of a subject. (Bougneres [0024])
Regarding claim 16, As discussed in MPEP § 2112, citing In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594), the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, there is reason to believe that Bougneres teaches the method claim 16 since Bougneres teaches each positively recited step of the method of claim 16, (see rejection of claim 1) but Bougneres simply did not make a record of the resulting increased levels of cortisol or aldosterone in their subjects to verify the claimed intended results. Just based on the identical method taught by Bourneres alone, there is reason to believe that the administration of the claimed 21OH rAAV vector to a subject would result in increasing the level of cortisol and/or aldosterone in that subject.
However, Bougneres does provide some indirect evidence that aldosterone did increase in their subjects. Bougneres teaches that 21 -hydroxylase (210H) is a cytochrome P450 enzyme, encoded by the CYP21A2 gene, that is involved with the biosynthesis of the steroid hormones aldosterone and cortisol. (Bougneres [0004]). Thus, it stands to reason that introducing a functioning 21OH gene to a subject would increase the production of aldosterone to at least some degree.
Bougneres did happen to measure the level of a related enzyme, aldosterone synthase, which is involved in producing aldosterone. Bougneres teaches that the expression of aldosterone synthase (Cypllb2) showed a 40-fold increase in the adrenals of Cyp21 / mice (i.e. mice that had been administered the claimed 21 OH vector) located in the zona glomerulosa (FIG. 3 A) (Bougneres [00179]). So, it is further reasonable that an increase in the expression of aldosterone synthase would result in the increase of aldosterone in a subject that had been administered the 21OH vector of claim 16 to at least some degree.
Regarding claim 17, Bougneres teaches a method of expressing 21 -hydroxylase (21 OH) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a rAAV particle comprising a rAAV vector comprising a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleotide sequence encoding a 21 -hydroxylase (21 OH) protein, the non-AAV nucleotide sequence operably linked to a promote. (Bougneres [0015]). Bougneres teaches that in some embodiments, rAAV vectors or rAAV particles comprising a nucleic acid sequence encoding 21 OH are administered to a subject at a dose ranging from about 1011 to about 1014 vg/kg body weight of the subject.
(Bougneres [00144]).
Bougneres teaches that within 5 weeks following injection of the CYP21 vector, the progesterone level decreased by 42% in a subject. (Bougneres, Example 6, [00184]).
Regarding claim 21, Bougneres teaches that in some embodiments, rAAV vectors or rAAV particles comprising a nucleic acid sequence encoding 21 OH are administered to a subject at a dose ranging from about 1011 to about 1014 vg/kg body weight of the subject.
(Bougneres [00144]).
Regarding claim 26, Bougneres teaches intravenous injection of their vector. (Bougneres, Example 5 [00180, 00181])
Regarding claim 30, Bougneres teaches that their rAAV vector may encode a 21 OH protein that is human 21 OH protein. (Bougneres, [0008]).
Regarding claim 33, Bougneres teaches the method of claim 1 wherein the non-AAV nucleotide sequence encodes the amino acid sequence of Seq ID NO:1 which is a 100% match for the claimed SEQ ID NO:1. (Bougneres, claim 6, SEQ ID NO:1).
Regarding claim 34, Bougneres teaches that their non- AAV nucleotide sequence is operably linked to a promoter, wherein the promoter directs expression of the 21 OH protein in a host cell ( e.g ., an adrenal gland cell or an adrenal cortex cell). (Bougneres [0009]).
Regarding claim 36, Bougneres teaches that non-limiting examples of suitable promoters include a cytomegalovirus/b- actin hybrid promoter, PGK promoter or a promoter specific for expression in an adrenal cortex cell. (Bougneres [0009]).
Regarding claim 40, Bougneres teaches that in certain cases, a rAAV vector of the invention is an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV 12, rhlO or rh74 serotype. (Bougneres [0011]).
Regarding claim 44, Bougneres teaches a method of expressing 21 -hydroxylase (21 OH) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a rAAV particle comprising a rAAV vector comprising a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleotide sequence encoding a 21 -hydroxylase (21 OH) protein, the non-AAV nucleotide sequence operably linked to a promote. (Bougneres [0015]). Bougneres teaches that in some embodiments, rAAV vectors or rAAV particles comprising a nucleic acid sequence encoding 21 OH are administered to a subject at a dose ranging from about 1011 to about 1014 vg/kg body weight of the subject.
(Bougneres [00144]).
Bougneres teaches that in certain cases, a rAAV vector of the invention may be AAV5. (Bougneres [0011]).
Bougneres teaches that the the non-AAV nucleotide sequence may encode the amino acid sequence of Seq ID NO:1 which is a 100% match for the claimed SEQ ID NO:1. (Bougneres, claim 6, SEQ ID NO:1).
Regarding claim 49, Bougneres teaches intravenous injection of their vector. (Bougneres, Example 5 [00180, 00181])
Regarding claim 50, Bougneres teaches that their method may be used to treat a subject with 21 -hydroxylase deficiency (Bougneres [00123, 00125, claim 22]).
Regarding claim 54, Bougneres teaches that non-limiting examples of suitable promoters include a cytomegalovirus/b- actin hybrid promoter, PGK promoter or a promoter specific for expression in an adrenal cortex cell. (Bougneres [0009]).
Regarding claim 61, Bougneres teaches that their method may be used to treat a subject that is affected with congenital adrenal hyperplasia (CAH). (Bougneres [0018]).
Regarding claim 63, Bougneres teaches that any type of inducible promoter which is tightly regulated and is specific for the particular target cell type in which 21 OH expression is desired may be used. Examples of inducible promoters regulated by exogenously supplied compounds, include the dexamethasone (Dex)-inducible mouse mammary tumor virus (MMTV) promoter. (Bougneres [00102]).
Bougneres teaches that Homozygous (Cyp21 / ) mice, heterozygous (Cyp2I ) and wild-type ( Cyp21+/+ ) littermates were used for the experiments and analyses. All dams received injections of 5 pg dexamethasone from gestational day 20 until postnatal day 7 of newborns. Pups were treated every 2 days with corticosterone (5 pg per day) and fludrocortisone (0.025 pg per day) until day 14. (Bougneres [00151]). Bougneres later subjected these steroid-administered mice to the method of claim 1 in later experiments (Bougneres Example 3, Example 5, Example 6).
Bougneres teaches the method of claim 1 further comprising the administration of a steroid (dexamethasone, corticosterone, fludrocortisone) to the subject.
Regarding claim 85, Bougneres teaches a method of expressing 21 -hydroxylase (21 OH) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a rAAV particle comprising a rAAV vector comprising a nucleic acid molecule comprising at least one AAV inverted terminal repeat (ITR) and a non-AAV nucleotide sequence encoding a 21 -hydroxylase (21 OH) protein, the non-AAV nucleotide sequence operably linked to a promote. (Bougneres [0015]). Bougneres teaches that in some embodiments, rAAV vectors or rAAV particles comprising a nucleic acid sequence encoding 21 OH are administered to a subject at a dose ranging from about 1011 to about 1014 vg/kg body weight of the subject.
(Bougneres [00144]).
Bougneres teaches that within 5 weeks following injection of the CYP21 vector, the progesterone level decreased by 42% in a subject. (Bougneres, Example 6, [00184]). (i.e., a lower level of progesterone in the subject after the administration of the rAAV, as compared to before administration of the rAAV).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
U.S. Patent No. 12195767 (US Application No. 16/962,552).
Claims 1-2, 5, 7, 21, 26, 30, 33, 34, 40, 44, 49-50, and 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 12, 14, 18, 22, 24, 26, 32, and 34, of U.S. Patent No. 12195767 (US Application No. 16/962,552). Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims recite administering a therapeutically effective amount of an rAAV particle to a subject, thereby treating 21OHD in the subject (Competing Claim22) intravenously (Competing Claim 24), where 21OH is expressed in the subjects adrenal cortex, adrenal stem cells, adrenal progenitor cells (Competing claim 21) where patient has CAH (Competing Claim 26).
The competing claims recite that the AAV comprises an ITR, and encodes 21OH with at least 95% identity to SEQ ID NO:1 (identical to SEQ ID NO:1 as the present case) (Competing Claim 1, 14, 18, 32, 34). The competing claims further recite that the 21OH protein is human and consists of SEQ ID NO: 1 (Competing Claim 2 -5), that the ITR may be AAV5 (Competing Claim 1, 12, 14).
Regarding the claimed dosage range in claim 1, and 21, the election of a particular therapeutically effective dosage would have been obvious to the skilled artisan as a part of routine optimization of adjusting a therapeutic dose to a particular patient. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Thus, these claims would be obvious in light of the competing claims for a therapeutically effective dosage of the 21OH rAAV.
Provisional Double Patenting
18/946,854
Claims 1, 2, 7, 30, 31, 34, 36, 40, 44, and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-7, 9, 10, 12-18, 20 and 22 of copending Application No. 18/946,854. Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims recite administering a therapeutically effective amount of rAAv 21OH vector to a subject (competing claim 20, 22). The competing claims recite that the rAAV may be an rAAV comprising an ITR and encoding a codon-optimized human 21OH operably linked to a promoter; where the 21OH protein may comprise SEQ ID NO:50 (the presently claim SEQ ID NO:50 is identical to the competing claim SEQ ID NO:50; that the promoter directs expression of the 21OH protein in a host cell; that the cell may be an adrenal cortex cell; that the promoter may be a CMV-beta-actin promoter; that the ITR or rAAV may be AAV1-12, (Competing claim 1-5, 7, 9, 10, 12-18). The competing claim recites the encoded 21OH may consist of SEQ ID NO:1, which is identical to the presently claimed SEQ ID NO:1 (Competing claim 6).
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-2, 5, 7, 16-17, 21, 26, 30, 33-36, 40, 44, 49-50, 54, 61, 63, and 85 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS RUSSE AMICK whose telephone number is (571)272-5474. The examiner can normally be reached 7:30-5 M-F.
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/THOMAS R. AMICK/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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