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 .
Response to Amendment
The preliminary amendment filed 04/25/2024 is acknowledged. Claims 1-45 are canceled and claims 46-81 are new. No restriction is being imposed in this case. Claims 46-81 are under examination.
Priority
The priority date of claims 46-81 is 12/11/2013.
Claim Rejections - 35 USC § 112(b)
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 46-81 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 46 recites “at least about” and claims 47-48 recite “about”. The MPEP instructs that when determining the range encompassed by the term “about,” one must consider the context of the term as it is used in the specification and claims of the application (see MPEP 2173.05(b)(III)(A). The specification discloses that the term about “may mean ±5% of the value being referred to”, but does not limit it to ±5%. In the absence of a clear indication as to what range of specific activity is covered by the term “about”, the metes and bounds of the claims cannot be known.
Claims 47-81 are also rejected for depending upon and indefinite claims without resolving the indefiniteness.
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 46-48, 50-66 and 68-81 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 the claimed methods comprising administering a viral vector comprising one or more regulatory elements operatively linked to a nucleic acid encoding a Mullerian Inhibiting Substance (MIS) protein, wherein said MIS is a wild-type feline MIS or wherein said MIS protein is set forth in amino acid residues 25-559 of SEQ ID NO: 4, does not reasonably provide enablement for the claims as broadly recited. 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 or use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The claims are broad with respect to the recited nucleic acid encoding the MIS protein. Independent claims 46 and 64 are drawn to a method of permanent contraception comprising administering a nucleic acid encoding MIS. The instant specification defines MIS variants broadly. See, for instance, p. 17, paragraph [0074]:
In some embodiments, a recombinant human MIS protein is at least 75%, at least 80%, at least 85%, at least 90% or at least 95% similar to the homologous recombinant human MIS protein…By way of example, a first amino acid sequence can be considered similar to a second amino acid sequence when the first amino acid sequence is at least 50%, 60%, 70%, 75%, 80%, 90%, or even 95% identical, or conservatively substituted, to the second amino acid sequence when compared to an equal number of amino acids as the number contained in the first sequence, or when compared to an alignment of polypeptides that has been aligned by a computer similarity program known in the art, as discussed below.
Thus, the specification encompasses MIS variants with as little as 50% similarity with the wild-type protein, as well as fragments and derivatives thereof (paragraphs [0073]-[0075]).
The specification discloses a single example of an MIS variant capable of carrying out the claimed contraception methods. Specifically, the instant specification discloses that the Q residue at position 450 of SEQ ID NO: 3 can be substituted with an R (see p. 81). The specification does not disclose, other than the Q→R mutation at residue 450 of SEQ ID NO: 3, how the MIS can be modified while maintaining the ability to act as a contraceptive. The evidence of record, which teaches only a single MIS variant capable of acting as a contraceptive, is not commensurate with the claims.
Applicant does not teach how up to 50% of residues can be mutated in in MIS which results in nucleic acids encoding for proteins capable of providing permanent contraception. The number of mutations generally possible in any given protein that can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g., such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. The art provides evidence that mutations can be destabilizing and their effects unpredictable. Bhattacharya et al. (PLoS ONE 12(3): e0171355. https://doi.org/10.1371/journal.pone. 0171355; 22 pages total—on IDS filed 08/07/2024) teach even single nucleotide variations have a “range of effects at the protein level that are significantly greater than assumed by existing software prediction methods, and that correct prediction of consequences remains a significant challenge” (p. 18, 1st and 2nd paragraphs). In addition, Fenton et al. (Medicinal Chemistry Research (2020) 29:1133–1146—on IDS filed 08/30/2024) review the unpredictability of making substitutions at non-conserved positions in a protein, which can have significant effects on protein function, that computational algorithms cannot predict very well (p. 1134, right column, middle paragraph).
Although machine learning algorithms have improved the ability to predict protein 3D structure from sequences, methods based on artificial intelligence for predicting the impact of mutations on protein stability still face challenges, including prediction biases towards “generalization”, “data set”, “destabilizing mutations” and the inability to predict the effects of multiple mutations. See Figure 1, at p. 162 and the discussion at pages 165-166 of Pucci et al. (Current Opinion in Structural Biology 2022, 72: 161-168). Even in the case of single mutations, artificial intelligence programs do not accurately “predict the impact of mutation on protein stability” or function (see p. 2, 2nd paragraph and p. 7, 1st full paragraph of Pak et al., PLoS ONE 18(3): e0282689. https://doi.org/10.1371/ journal.pone.0282689).
In the instant case, the claims encompass nucleic acids encoding MIS proteins that are up to 50% divergent from wild-type MIS. Applicants have provided little or no guidance beyond the mere presentation of sequence data to enable one of ordinary skill in the art to determine, without undue experimentation, the positions in the protein which are tolerant to change by amino acid substitutions or deletions, and the nature and extent of changes that can be made in these positions. Although the specification outlines art-recognized procedures for producing and screening for active muteins, this is not adequate guidance as to the nature of active derivatives that may be constructed, but is merely an invitation to the artisan to use the current invention as a starting point for further experimentation. Thus, screening all of the possible MIS variants, fragments and derivatives for the ability to act as a contraceptive would require an undue amount of experimentation.
Due to the large quantity of experimentation necessary to test all of the encompassed MIS variants, fragments and derivatives for the ability to act as a contraceptive, the lack of direction/guidance presented in the specification regarding any additional mutations beyond the Q→R mutation at residue 450 of SEQ ID NO: 3, the absence of working examples directed to same, the unpredictability of the effects of mutation on protein structure and function, and the breadth of the claims which fail to recite limitations on mutations and alterations to the administered nucleic acid encoding MIS protein, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention in its full scope.
Written Description
Claims 46-48, 50-66 and 68-81 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 claims contain 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. This is a written description rejection.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. Independent claims 46 and 64 are drawn to a method of permanent contraception comprising administering a nucleic acid encoding MIS. The instant specification defines MIS variants broadly. See, for instance, p. 17, paragraph [0074]:
In some embodiments, a recombinant human MIS protein is at least 75%, at least 80%, at least 85%, at least 90% or at least 95% similar to the homologous recombinant human MIS protein…By way of example, a first amino acid sequence can be considered similar to a second amino acid sequence when the first amino acid sequence is at least 50%, 60%, 70%, 75%, 80%, 90%, or even 95% identical, or conservatively substituted, to the second amino acid sequence when compared to an equal number of amino acids as the number contained in the first sequence, or when compared to an alignment of polypeptides that has been aligned by a computer similarity program known in the art, as discussed below.
Thus, the specification encompasses MIS variants with as little as 50% similarity with the wild-type protein, as well as fragments and derivatives (see paragraphs [0073]-[0075]).
The MPEP 2163(A) states “‘[a]n invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.’” For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. (See MPEP 2163(II)(A)(3)(a)(i)). In deciding whether the application complies with the written description requirement of 35 USC 112(a) or 35 USC 112 (pre-AIA ), first paragraph, it is necessary to understand what Applicant is claiming (see above) and what Applicant has possession of. From the specification, it is clear that Applicant has possession of a single example of an MIS protein variant capable of carrying out the claimed contraception methods. Specifically, the instant specification discloses that the Q residue at position 450 of SEQ ID NO: 3 can be substituted with an R (see p. 81). The specification does not disclose, other than the Q→R mutation at residue 450 of SEQ ID NO: 3, how the MIS protein can be modified while maintaining the function as a contraceptive. Given the limited teachings, the instant specification does not provide sufficient evidence that the inventors are in possession of the genus of MIS variants that can be fragments or derivatives and/or differ from the wild-type protein by up to 50% and still be capable of acting as a contraceptive. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). With the exception of SEQ ID NO: 4, which incorporates the Q→R mutation at residue 450, the skilled artisan cannot envision the detailed chemical structure of the encompassed nucleic acids encoding MIS polypeptides, fragments, and variants, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, only isolated polypeptides comprising the amino acid sequence set forth in SEQ ID NO: 4, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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.
US Patent 11,998,590
Claims 46-51, 54-69 and 72-81 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 11,998,590 in view of Balance (EP2216409; application published 08/11/2010). The claims of the US Patent 11,998,590 are drawn to a method of permanent contraception in a female cat or arresting folliculogenesis in a female cat comprising administering an effective amount of a composition comprising a viral vector comprising one or more regulatory elements operatively linked to a nucleic acid encoding a wild-type feline Mullerian Inhibiting Substance (MIS), wherein the effective amount of the composition administered to the female cat increases the concentration of MIS protein in the blood of the female cat to a MIS serum concentration of about 0.3 μg/ml to about 5 μg/ml (claims 1, 2, 14, 15), or about 0.3 μg/ml to about 1.5 μg/ml (claim 20, 21), which also encompasses a concentration ranges of 2- to 5-fold higher or more than 5-fold higher, wherein the viral vector is an adenoviral vector, an adeno-associated virus (AAV) vector, a poxvirus vector, or a lentiviral vector (claims 3-5, 16, 17, 22, 23), wherein the one or more regulatory elements comprise a promoter element, an enhancer element and a constit11utively active promoter (claims 6-8, 24-26), wherein the composition further comprises a pharmaceutically acceptable carrier and the administering is intravenous, subcutaneous, or intramuscular administration and a one-time injection (claims 9-13, 18, 19, 27-31).
The differences between the instant claims and the claims of the reference patent are as follows. As noted above, the MIS concentration range increases recited in the claims of the reference patent suggest between a 2- to 5-fold increase or a more than 5-fold increase in MIS concentration. Further, the claims of the reference patent, which recite a wild-type MIS, are narrower in scope than the instant claims, and are therefore anticipatory. The claims of the reference patent do not recite that the MIS protein comprises an albumin leader sequence. Ballance teaches how to construct a fusion protein conjugated to an albumin leader sequence (see paragraph [0716]). It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the MIS protein by fusing to an albumin leader sequence because Ballance teaches that albumin fusions are stabilizing (see paragraph [0002]). The person of ordinary skill in the art would have been motivated to attach an albumin leader sequences because albumin is “a carrier molecule and its inert nature are desirable properties for use as a carrier and transporter of polypeptides” (see paragraph [0004]). Furthermore, the person of ordinary skill in the art could have reasonably expected success for this reason. Therefore, when read in light of the prior art of Ballance, the instant claims are not patentably distinguishable from those of the prior art.
US Patent 11,135,269
Claims 46-81 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,135,269 in view of Durlinger et al. (Endocrinology 140: 5789–5796, 1999—on IDS filed 08/07/2024), Grootegoed (EP1074265—on Applicant IDS filed 08/07/2024), Donahoe et al. (WO 01/19387—on IDS filed 08/07/2024), Zincarelli et al. (Mol Ther. 2008;16(6):1073-80—on IDS filed 08/07/2024) and Ballance (EP2216409—cited above). The claims of the reference patent are drawn to administering (I) recombinant MIS protein for reducing a decline in functional ovarian reserve (claims 1-7) and (II) a method of contraception comprising administering to the female cat or dog a recombinant MIS protein or a viral vector comprising a promoter, operatively linked to a nucleic acid encoding a recombinant MIS protein, wherein the nucleic acid comprises SEQ ID NO: 1 (LR-MIS) or having at least 95% sequence identity to the nucleic acid sequence of SEQ ID NO: 1 (LR-MIS), or a comprises nucleic acid sequence of at least 95% sequence identity to nucleotides 79-1680 of SEQ ID NO: 1, where nucleic acids 1-78 of SEQ ID NO: 1 are replaced by nucleic acid sequences encoding leader sequences corresponding to SEQ ID NOs: 8-20 (claims 8-12). The claims of the reference patent and the instant claims are both drawn to a method of contraception in a cat or dog comprising administering a viral vector comprising a promoter, operatively linked to a nucleic acid encoding the MIS protein, wherein the viral vector is selected from the group consisting of; an adenoviral vector, an AAV vector, a poxvirus vector and a lentiviral vector.
The second factor to consider is to ascertain the differences between the claims of the reference patent and those of the instant claims. The claims of the reference patent are narrower with respect to the recited MIS protein/nucleic acid, and are therefore anticipatory. Further, the claims of the reference patent recite that the MIS protein/nucleic acid has improved cleavage properties with respect to wild-type, and therefore, one having ordinary skill in the art would be motivated to substitute the wild-type for the variant recited in the reference patent.
(i) While the claims of the reference patent recite the MIS serum concentration achieved by administration of the protein (a 2 to 5-fold higher or more than 5-fold higher in claim 6(c) or between 1 µg/ml-5µg/ml in claim 6(d)) in order to reduce a decline in the functional ovarian reserve (FOR), they do not recite the serum concentration achieved by administration of the protein or nucleic acid in order to achieve contraception. (ii) In addition, the claims of the reference patent do not specify a permanent method of contraception, nor the type of vector, promoter or regulatory elements. (iii), Finally, the claims of the reference patent do not recite that the MIS protein comprises an albumin leader sequence.
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that the concentration of MIS protein in the blood in order to achieve contraception should be the same or similar to that of reducing a decline in the FOR for the following reason. First, it was well known in the art that the FOR was the stock of primordial follicles. Durlinger et al. teach that “[p]rimordial follicles can be considered the ovarian follicle stock, and this reserve of dormant follicles is not renewable”, thereby defining the FOR (see p. 5795, left column, 2nd paragraph). Durlinger et al. teach that in AMH (aka MIS) null mice, the primordial follicle pool is more quickly depleted than in wild-type mice (see abstract; p. 5791, right column, penultimate paragraph; Figure 1; p. 5793, Figure 3A-3C). Thus, lack of AMH in the null mice leads to premature depletion of FOR.
The person of ordinary skill in the art upon reading the claims of the reference patent in light of what was known about the depletion of FOR would have recognized that MIS concentration in the blood capable of reducing the decline in FOR would be similar to the concentration necessary for contraception because keeping the ovarian follicle stock in a quiescent state would also achieve the goal of blocking primordial follicles from growing into primary, preantral and then antral (mature) follicles capable of being ovulated and fertilized. This was also recognized in the patent publication of Grootegoed, who taught therein that administration of AMH/MIS to inhibit recruitment of primordial follicles, would serve as contraception or delay menopause (i.e., reduce the decline in the FOR—see abstract; paragraph [0016]; [0018]; [0039]; claim 2). In summary, the person of ordinary skill in the art, upon reading all of the claims of the reference patent in light of what was known in the art with respect to FOR could have reasonably expected that achieving an MIS concentration of between 1 µg/ml-5µg/ml as recited in claim 6, would also achieve contraception.
(ii) Regarding the type of vector, promoter or regulatory elements, the ‘387 document teaches administering a viral vector comprising regulatory elements operatively linked to a nucleic acid encoding the wild-type MIS (see p. 17, lines 12-17; p. 18, lines 20-30 through p. 19, lines 1-6; p. 26, lines 14-30 through p. 27, lines 1-10). The ‘387 document contemplates pharmaceutically acceptable carriers (p. 11, lines 1-14 of the ‘387 document) and various types of injection (intravenous, intramuscular, subcutaneous) as well as “continuous infusion, or by single or multiple boluses”, thus encompass a “one-time injection” (p. 14, lines 23-25; p. 27, lines 1-4; lines 18-22). The ‘387 document also teaches a CMV promoter (see p. 18, last paragraph), thus encompassing a constitutively active promoter. The person of ordinary skill in the art could have reasonably expected success because the ‘387 document contemplates treatment of polycystic ovarian disease comprising administering the viral vector encoding the MIS protein, thus the targeted organ, the ovary, is the same in both of the applied prior art references.
Regarding the AAV9 viral vector, Zincarelli et al. teach an evaluation of the AAV serotypes 1-9 in gene expression in mice. Zincarelli et al. note that using the AAV9 viral vector resulted in “the best viral genome distribution and highest protein levels” (see abstract). Zincarelli et al. also show a schematic of promoter/enhancer structure (p. 1074, Figure 1a). It would have been obvious to the person of ordinary skill in the art, upon reading the claims of the reference patent to use the AAV9 vector, because Zincarelli et al. teach that “AAV9-injected animals show the maximum vector expression” (see p. 1075, left column, 1st paragraph). See also Figure 3 at p. 1075 of Zincarelli and colleagues. The person of ordinary skill in the art would have been motivated to use the AAV9 vector because of its high expression sustained over a long period of time, which is practical when delivering MIS for the purpose of contraception. Furthermore, for the same reason, namely good protein expression for an extended period of time, the person of ordinary skill in the art could have reasonably expected success in using the AAV9 viral vector to deliver MIS for the purpose of contraception. Finally, the difference between administering a viral vector to a cat/dog to achieve “permanent contraception” vs. “contraception” is not a patentably distinguishable difference. The use of the AAV9 viral vector, which can deliver good protein expression for an extended period of time could be expected to approach a long term or permanent contraception.
(iii) Regarding the albumin leader sequence, Ballance teaches how to construct a fusion protein conjugated to an albumin leader sequence (see paragraph [0716]). It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the MIS protein by fusing to an albumin leader sequence because Ballance teaches that albumin fusions are stabilizing (see paragraph [0002]). The person of ordinary skill in the art would have been motivated to attach an albumin leader sequences because albumin is “a carrier molecule and its inert nature are desirable properties for use as a carrier and transporter of polypeptides” (see paragraph [0004]). Furthermore, the person of ordinary skill in the art could have reasonably expected success for this reason.
Therefore, when read in light of the supporting prior art documents, the instant claims are not patentably distinct from those of the reference patent.
Application No. 18/283,556
Claims 46-81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-6, 8, 11, 14, 16-18, 20, 23-25, 27-29, 31, 32, 34, 35, 39, 42, 43, 46, 47, 49, 50 and 62 of copending Application No. 18/283,556 in view of Zincarelli et al. (Mol Ther. 2008;16(6):1073-80—cited above) and Ballance (EP2216409—cited above). The claims of the reference application are drawn to a method of reducing fertility or providing long term sterility in a prepubescent non-human subject (e.g., kitten or puppy) comprising administering to the subject an effective amount of a composition comprising a stable, injectable vector comprising a nucleic acid encoding a Mullerian Inhibiting Substance (MIS) protein operatively linked to one or more regulatory elements, wherein the MIS protein comprises: a wild-type feline MIS protein, a feline MIS protein comprising a non-MIS leader sequence in place of amino acids 1-21 of SEQ ID NO: 1 or of SEQ ID NO: 18, or a chimeric feline MIS protein comprises a protein having at least 85% sequence identity to amino acids 22-572 of SEQ ID NO: 3, and wherein amino acid residue Q at position 465 of SEQ ID NO: 3 is changed from a Q to a R (arginine),wherein the vector is an adenoviral vector, an adeno-associated virus (AAV) vector, a poxvirus vector, or a lentiviral vector, wherein the one or more regulatory elements comprise; a) a promoter element; b) a promoter element and an enhancer element; and/or c) a constitutively active promoter, wherein the composition comprises a pharmaceutically acceptable carrier and the administering is via intravenous, subcutaneous, intramuscular administration or via a single one-time injection. The claims of the reference application also recite a vector comprising a nucleic acid encoding a feline Mullerian Inhibiting Substance (MIS) protein operatively linked to one or more regulatory elements.
The difference between the instant claims and those of the reference application are as follows. The claims of the reference application do not recite the effects of administering on serum MIS concentrations, however, the same agent is administered to the same patient population in order to achieve contraception (reduced fertility) or sterility, thus the effects on serum concentration would be expected to be the same. The claims of the reference application are more specific with respect to the encompassed MIS proteins/nucleic acids, and thus are anticipatory. The claims of the reference patent do not recite (i) the vector is AAV9 or that the (ii) leader sequence is an albumin leader sequence.
(i) Regarding the AAV9 viral vector, Zincarelli et al. teach an evaluation of the AAV serotypes 1-9 in gene expression in mice. Zincarelli et al. note that using the AAV9 viral vector resulted in “the best viral genome distribution and highest protein levels” (see abstract). Zincarelli et al. also show a schematic of promoter/enhancer structure (p. 1074, Figure 1a). It would have been obvious to the person of ordinary skill in the art, upon reading the claims of the reference application to use the AAV9 vector, because Zincarelli et al. teach that “AAV9-injected animals show the maximum vector expression” (see p. 1075, left column, 1st paragraph). See also Figure 3 at p. 1075 of Zincarelli and colleagues. The person of ordinary skill in the art would have been motivated to use the AAV9 vector because of its high expression sustained over a long period of time, which is practical when delivering MIS for the purpose of contraception. Furthermore, for the same reason, namely good protein expression for an extended period of time, the person of ordinary skill in the art could have reasonably expected success in using the AAV9 viral vector to deliver MIS for the purpose of contraception. The use of the AAV9 viral vector, which can deliver good protein expression for an extended period of time could be expected to approach a long term or permanent contraception.
(ii) Regarding the albumin leader sequence, Ballance teaches how to construct a fusion protein conjugated to an albumin leader sequence (see paragraph [0716]). It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the MIS protein by fusing to an albumin leader sequence because Ballance teaches that albumin fusions are stabilizing (see paragraph [0002]). The person of ordinary skill in the art would have been motivated to attach an albumin leader sequences because albumin is “a carrier molecule and its inert nature are desirable properties for use as a carrier and transporter of polypeptides” (see paragraph [0004]). Furthermore, the person of ordinary skill in the art could have reasonably expected success for this reason. Therefore, when read in light of the prior art of Ballance, the instant claims are not patentably distinguishable from those of the prior art.
Therefore, when read in light of the prior art the instant claims are not patentably distinct from those of the reference application. This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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