DETAILED ACTION
Claims 1-33 are pending and being examined on the merits in this office 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 .
Priority
The filing receipt dated 8/06/2024 provides the following information:
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Specification
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See e.g., paras. [0092], [0140], and [0147].
Claim Objections
Claims 1-3, 10, 16, and 23 are objected to because of the following informalities:
Claims 1, 16, and 23 should be amended to recite:
“the step of administering to said subject in need thereof a composition comprising”….
(SEQ ID NO:1)
For each of the recited peptides, the SEQ ID NOs should be placed in parentheses after each peptide sequence. The claim should further be amended to not include applicant’s internal nomenclature for the peptides. Peptide should only be associated with a SEQ ID NO: that identifies a specific peptide in a defined amino acid sequence, per the Sequence Listing.
Further regarding claim 1, the acronym CNP should be written out in full name in the first appearance in the claims, e.g., “C-type natriuretic peptide (CNP)”.
Regarding claim 2, the acronym “QCT” should be written out in full name in the first appearance in the claims.
Claim 3 should be amended to recite “is selected from campomelic
Claim 10 should be amended to recite “the CNP peptide” for consistency with claim 1.
Appropriate correction is required.
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.
Claims 2, 7, 10-13, 15, 20, 22, 28, 30, and 31 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 2 recites the limitation "the treatment". There is insufficient antecedent basis for this limitation in the claim.
The term “about” in claims 7, 10, 12, 13, 15, 20, 22, 28, and 30 is a term of approximation which renders these claims indefinite. The term “about” is not defined by the claim, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification defines “about” as meaning an acceptable error for a particular value as determined by one of ordinary skill in the art, and provides several percentage ranges “about” may mean, but does not provide an objective numerical standard for assessing “about”.
The metes and bounds of claim 11 are deemed to be indefinite dues to alternate claim interpretation. Claim 11 recites “wherein the formulation comprises citric acid monohydrate or sodium citrate dihydrate, trehalose dihydrate or D-mannitol, L-methionine and polysorbate 80”. Multiple recitation of the terms “or” and “and” lead to alternative claim interpretation. The skilled artisan in not apprised of the exact components of the claimed formulation.
Because claims 12 and 13 depend from indefinite claim 11 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112(b).
Examiner recommends that claim 11 be amended to delete the multiple “or” within the claim and insert commas instead. Alternatively, Applicant should amend the claim to insert Roman numerals, e.g., a formulation comprising i) citric acid monohydrate or sodium citrate dihydrate, ii) trehalose dihydrate or D-mannitol, iii) L-methionine and iv) polysorbate 80. Claims 12 and 13 should be amended to include semi-colons to separate the distinct claim elements, and improve claim clarity.
Claim 31 recites the limitation "the upper body". There is insufficient antecedent basis for this limitation in the claim. Examiner recommends that claim 31 be amended to recite “change in [[the]] upper body length” at ll. 2, 4, and 6.
Claim Rejections - 35 USC § 102
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.
Claims 1-11, 14-21, 23-29, and 31-33 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wendt et al (U.S. 2010/0297021- cited in IDS filed 7/26/2024).
Wendt teaches C-type natriuretic peptide (CNP) pharmaceutical compositions comprising CNP variants, which are stated to be useful as therapeutic agents for skeletal dysplasias, such as achondroplasia and hypochondroplasia (abstract; paras. [0569]-0571], claims 1-3, 7). The reference teaches methods of treating a bone-related disorder or skeletal dysplasia comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the CNP variant peptide. Wendt discloses several doses at which CNP variants may be administered which are over 7.5 µg/kg (para. [0156]). CNP variants of SEQ ID NO:182, 192, 186, 181, 145, 191 and 75 have 100% identity with instantly claimed SEQ ID NOs:1-7, respectively. Accordingly, the limitations of instant claims 1 and 3 are satisfied.
Regarding claim 2, treatment comprising administration of the claimed CNP can yield an improvement in symptoms of increased growth velocity, increases long bone growth, and increased bone mineral density (paras. [[0155], [0567]-[0602], [0753], [0776], Ex 15-16, Figs 69-70). Regarding claims 4 and 5, the peptide can be administered daily, e.g., at least 6 months (paras. [[0156]-[0158], [0597]-[0602]). Regarding claim 6, the peptide can be administered subcutaneously or parenterally (paras. [0151]-[0158], [0333], [0590], [0602]-[0613], Ex 10). Regarding claim 7, the peptide can be administered at daily doses of 20, 30, 40, … 800 ug/kg, or about 1 mg/kg, 1.25 mg/kg, 1.5 mg/kg, 2 mg/kg or other dose deemed appropriate by the treating physician. The doses of CNP variants described herein can be administered according to the dosing frequency/frequency of administration described herein, including without limitation daily (para. [0156]).
Regarding claim 8, Wendt teaches that the pharmaceutical compositions can comprise a buffering agent, and isotonicity agent, a stabilizer, and anti-adsorbent agent (paras. [0577]-[0602]). Regarding claim 9, the formulations can be lyophilized, is a liquid form or reconstituted form (paras. [0589]-[0595]). Regarding claim 10, the formulation can comprise 2.0 mg/ml of the CNP peptide (para. [0581]). Regarding claim 11, Wendt teaches that a lyophilized formulation can be prepared that comprises any combinations of the gradients and their amounts or concentrations in tables 16 or 17; for example, a buffer can be a citric acid/citrate buffer at a concentration range of 10 mg/ml ± 9.9 mg/ml, pH 4 to 6; an isotonically-adjusting agent/bulking agents such as mannitol at a concentration range of 5%±3%, a stabilizer can be methionine at a concentration range of 0.01%-0.02%; and an antibiotic bent can be polysorbate 80 at a concentration range of 0.001%-0.5%.
Regarding claim 14, the formulation can be preservative free. Specifically, Wendt teaches that the preservative is optional, not that the preservative is a required or critical element of the formulations. Regarding claim 15, the formulation can have a pH of between 5-6 (paras. [0582]).
Regarding claim 16, Wendt teaches C-type natriuretic peptide (CNP) pharmaceutical compositions comprising CNP variants, which are stated to be useful as therapeutic agents for skeletal dysplasias, such as achondroplasia (Abstract). Wendt further teaches that the disclosure provides methods of treating comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the same may be useful for treating conditions or disorders responsive to CNP, including utility for elongating a bone or increasing long bone growth (para. [0155], [0566-[0571]). Wendt further discloses several doses at which CNP variants may be administered which are over 7.5 µg/kg (para. [0156]). CNP variants of SEQ ID NO:182, 192, 186, 181, 145, 191 and 75 have 100% identity with instantly claimed SEQ ID NOs:1-7, respectively.
Regarding claim 23, Wendt teaches C-type natriuretic peptide (CNP) pharmaceutical compositions comprising CNP variants, which are stated to be useful as therapeutic agents for skeletal dysplasias, such as achondroplasia (abstract). Wendt further teaches that the disclosure provides methods of treating comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the same may be useful for increasing growth velocity (Ex 15, Table 14, Fig 69). Wendt further discloses several doses at which CNP variants may be administered which are over 7.5 µg/kg (para. [0156]). CNP variants of SEQ ID NO:182, 192, 186, 181, 145, 191 and 75 have 100% identity with instantly claimed SEQ ID NOs:1-7, respectively.
Regarding claims 17, 18, 25, and 26, the peptide can be administered daily, e.g., at least 6 months (paras. [[0156]-[0158], [0597]-[0602]). Regarding claims 19 and 27, the peptide can be administered subcutaneously or parenterally (paras. [0151]-[0158], [0333], [0590], [0602]-[0613], Ex 10). Regarding claims 20 and 28, the peptide can be administered at daily doses of 20, 30, 40, … 800 ug/kg, or about 1 mg/kg, 1.25 mg/kg, 1.5 mg/kg, 2 mg/kg or other dose deemed appropriate by the treating physician. The doses of CNP variants described herein can be administered according to the dosing frequency/frequency of administration described herein, including without limitation daily (para. [0156]). Regarding claims 21 and 29, Wendt teaches that the pharmaceutical compositions can comprise a buffering agent, and isotonicity agent, a stabilizer, and anti-adsorbent agent (paras. [0577]-[0602]).
Regarding claims 24 and 31, the claimed results of administration are not expressly taught by Wendt. However, the claimed effects would naturally flow from administering the same CNP variants to the same population in the same amounts as in the instant claims.
MPEP § 2112 states:
The express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983).
MPEP § 2112(II) further states:
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)
Applicant is reminded that chemical compounds and their properties are inseparable. See MPEP 2112.01(II).
Regarding claim 32, the peptide can be administered subcutaneously or parenterally (paras. [0151]-[0158], [0333], [0590], [0602]-[0613], Ex 10). Regarding claim 33, the peptide can be administered daily or multiple times per week) is for 3 days, 1 week, 2 weeks, 3 weeks, etc (paras. [[0156]-[0158], [0597]-[0602]).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wendt et al (U.S. 2010/0297021- cited in IDS filed 7/26/2024).
Wendt teaches C-type natriuretic peptide (CNP) pharmaceutical compositions comprising CNP variants, which are stated to be useful as therapeutic agents for skeletal dysplasias, such as achondroplasia and hypochondroplasia (abstract; paras. [0569]-0571], claims 1-3, 7) [instant claim 1]. The reference teaches methods of treating a bone-related disorder or skeletal dysplasia comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the CNP variant peptide [instant claim 1]. Wendt further teaches that the disclosure provides methods of treating comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the same may be useful for treating conditions or disorders responsive to CNP, including utility for elongating a bone or increasing long bone growth (para. [0155], [0566-[0571]) [instant claim 16]. Wendt further teaches that the disclosure provides methods of treating comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the same may be useful for increasing growth velocity (Ex 15, Table 14, Fig 69) [instant claim 23]. Wendt discloses several doses at which CNP variants may be administered which are over 7.5 µg/kg (para. [0156]). CNP variants of SEQ ID NO:182, 192, 186, 181, 145, 191 and 75 have 100% identity with instantly claimed SEQ ID NOs:1-7, respectively.
Wendt teaches that a formulation can be prepared that comprises any combinations of the gradients and their amounts or concentrations in tables 16 or 17; for example, a buffer can be a citric acid/citrate buffer at a concentration range of 10 mg/ml ± 9.9 mg/ml, pH 4 to 6; an isotonically-adjusting agent/bulking agents such as mannitol at a concentration range of 5%±3%, a stabilizer can be methionine at a concentration range of 0.01%-0.02%; and polysorbate 80 at a concentration range of 0.001%-0.5%. Wendt further teaches that trehalose can be a bulking agent (e.g., para [0591]).
Wendt does not expressly teach the concentrations recited in claims 12, 13, 22, and 30.
It would have been obvious to one of ordinary skill in the art to optimize result effective variables such as concentration of recited components within the formulation (e.g., citric acid, mannitol, methionine). The MPEP states the following: 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 re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Therefore, it would have been obvious to optimize the concentrations of citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80 to achieve optimal activity and therapeutic effectiveness of the CNP in patients. There is a motivation to optimize since it is normal desire of scientists or artisans to improve upon what is already generally known with a reasonable expectation that optimization would at least work the same.
Accordingly, instant claims 12, 13, 22, and 30 are rendered obvious.
Claims 1-33 are obvious in view of the teachings of the cited reference.
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.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 12-17 of U.S. Patent No. 8,198,242 (hereinafter referred to as “the ‘242 patent”), in view of over Wendt et al (U.S. 2010/0297021- cited in IDS filed 7/26/2024).
Instant claims 1-4, 6-13, and 15, 16, 23, and 31-33 are directed to a method of treating skeletal dysplasia comprising administration of a composition comprising a CNP variant, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7; claim 2 recites the limitation that the treatment results in an improvement of increased absolute growth, and increased long-bone growth. Claim 16 is directed to a method of increasing long bone growth comprising administration of a composition comprising a CNP variant, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7. Claims 16, 23, and 31-33 are directed to a method of increasing growth velocity comprising administration of a composition comprising a CNP variant, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7.
Claims 1-3, 12, 13, and 17 of the ‘242 patent recite CNP variants which have 100% identity to the variants of SEQ ID NOs:1-7 as recited in instant claims. Claims further recite pharmaceutical compositions, and formulations and excipients comprising the CNP variant peptides. Claims 4 and 14 of the ‘242 patent recites a method of treating bone -related disorder of skeletal disease, e.g., achondroplasia. Claims 15 and 16 of the ‘242 patent recite a method of increasing long bone growth comprising the CNP variant peptides.
The claims of the ‘242 patent do not expressly teach administration of “at least 7.5 μg/kg CNP variant peptide”.
Wendt et al teach methods of treating conditions or disorders responsive to CNP, comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the same to a subject in need thereof. CNP variants of SEQ ID NO:182, 192, 186, 181, 145, 191 and 75 have 100% identity with instantly claimed SEQ ID NOs:1-7, respectively. The reference teaches administration of CNP doses of 7.5 μg/kg (e.g., para. [0155). Wendt et al further teaches administration of CNP variant peptides increases growth velocity and can be used to treat hypochondroplasia (paras. [0569], [0753], Fig. 69, claim 7).
It would have been obvious to one of ordinary skill in the art to modify the claims of the ‘242 patent by administering CNP doses, as taught by Wendt et al. The CNP variant peptides and pharmaceutical compositions of the ‘242 patent can be used in the instant claims. Examiner further notes that the instant case is analogous to Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Company (Fed. Cir. July 28, 2010), where the courts ruled that obviousness-type double patenting exist between previously-disclosed, but newly-claimed utility.
Accordingly, the instant claims are rendered obvious by the claims of the ‘242 and Wendt et al.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10646550 (hereinafter “the ‘550 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other the following reasons. The instant application is a child of the ‘550 patent.
Instant claims 1-15 are directed to a method of treating skeletal dysplasia comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7; claim 2 recites the limitation that the treatment results in an improvement of increased absolute growth, and increased long-bone growth. Claims 16-22 are directed to a method of increasing long bone growth comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7. Claim 23-33 are directed to a method of increasing growth velocity comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7.
Claims 1-13 of the ‘550 patent are drawn to a method of treating skeletal dysplasia in a subject comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein the CNP variant peptide is selected from the group consisting of SEQ ID NOs:1-7, wherein said composition comprises a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80, and wherein the step of administering treats said skeletal dysplasia. Claim 2 of the ‘550 patent recites treatment results in an improvement of increased absolute growth, increase growth velocity, and increased long-bone growth. Claim 3 of the ‘550 patent recites scope of diseases including achondroplasia and hypochondroplasia. Claims 4-6 of the ‘550 patent recites routes of administration in the treatment regimen/dosing schedule. Dependent claim 8 of the ‘550 patent wherein the formulation is lyophilized, is in liquid form, or is reconstituted from a lyophilized formulation. Dependent claim 9 of the ‘550 patent recite that the composition comprises at least about 2.0 mg/ml of the CNP peptide variant. Dependent claims 10 and 11 of the ‘550 patent recite specific concentrations for the citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80. Dependent claim 12 of the ‘550 patent recites that the formulation is preservative free. Dependent claim 13 of the ‘550 patent recite that the formulation is a pH of between 5 and 6.
Accordingly, instant claims 1-33 are rendered obvious by claims 1-13 of the ‘550 patent.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9907834 (hereinafter “the ‘834 patent”), in view of over Wendt et al (U.S. 2010/0297021- cited in IDS filed 7/26/2024). The instant application is a child of the ‘834 patent.
Instant claims 1-15 are directed to a method of treating skeletal dysplasia comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7; claim 2 recites the limitation that the treatment results in an improvement of increased absolute growth, and increased long-bone growth. Claims 16-22 are directed to a method of increasing long bone growth comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7. Claim 23-33 are directed to a method of increasing growth velocity comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7.
Claims 1-8 of the ‘834 patent are drawn to a formulation comprising (a) a CNP variant selected from the group consisting of SEQ ID NOs:1-7 and (b) citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80. Dependent claims 2 and 3 of the ‘834 patent recite that the formulation is lyophilized and/or is in a liquid form or reconstituted from a lyophilized formulation. Dependent claims 5 and 6 of the ‘834 patent recite specific concentrations for the citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80. Dependent claim 7 of the ‘834 patent recites that the formulation is preservative free. Dependent claim 8 of the ‘834 patent recites that the formulation is a pH of between 5 and 6.
The claims of the ‘834 patent do not expressly teach administration of “at least 7.5 μg/kg CNP variant peptide”.
Wendt et al teach methods of treating conditions or disorders responsive to CNP, comprising administering a therapeutically effective amount of a CNP variant or a composition comprising the same to a subject in need thereof. CNP variants of SEQ ID NO:182, 192, 186, 181, 145, 191 and 75 have 100% identity with instantly claimed SEQ ID NOs:1-7, respectively. The reference teaches administration of CNP doses of 7.5 μg/kg (e.g., para. [0155). Wendt et al further teaches administration of CNP variant peptides increases growth velocity and can be used to treat hypochondroplasia (paras. [0569], [0753], Fig. 69, claim 7).
It would have been obvious to one of ordinary skill in the art to modify the claims of the ‘834 patent by administering CNP doses for use in methods of treatment, as taught by Wendt et al. The CNP variant peptides formulations of the ‘834 patent can be used in the instant claims. Examiner further notes that the instant case is analogous to Sun Pharmaceutical Industries, Ltd. v. Eli Lilly and Company (Fed. Cir. July 28, 2010), where the courts ruled that obviousness-type double patenting exist between previously-disclosed, but newly-claimed utility.
Accordingly, the instant claims are rendered obvious by the claims of the ‘834 patent and Wendt et al.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 11590204 (hereinafter referred to as “the ‘204 patent”). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons. The instant application is a CON of the ‘204 patent.
Instant claims 1-15 are directed to a method of treating skeletal dysplasia comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7; claim 2 recites the limitation that the treatment results in an improvement of increased absolute growth, and increased long-bone growth. Claims 16-22 are directed to a method of increasing long bone growth comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7. Claim 23-33 are directed to a method of increasing growth velocity comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7.
Claims 1-7 of the ‘204 patent are drawn to a formulation comprising (a) a C-type natriuretic peptide (CNP) variant selected from the group consisting of SEQ ID NOs: 1-7, and (b) citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80, wherein the formulation comprises less than 2.0 mg/ml of said CNP peptide variant. Claims 8-14 of the ‘204 patent are drawn to a formulation comprising (a) a C-type natriuretic peptide (CNP) variant selected from the group consisting of SEQ IDS NOs: 1-7, and (b) citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80, wherein the formulation comprises about 0.5 to about 2.0 mg/ml of said CNP peptide variant. Claims 14-22 of the ‘204 patent are drawn to a formulation comprising (a) a C-type natriuretic peptide (CNP) variant selected from the group consisting of SEQ IDS NOs: 1-7, and (b) citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80, wherein the formulation comprises 10.0 mg/ml±9.9 mg/ml of said CNP peptide variant. Claims 23-31 of the ‘204 patent are drawn to a method of treating skeletal dysplasia (e.g., achondroplasia and hypochondroplasia) comprising the recited CNP formulations. Claim 29 of the ‘204 patent recites that a subject is administered at least 7.5 μg/kg per day to 60 μg/kg per day of said CNP variant. Claims 30 to 33 of the ‘204 and are drawn to a method of increasing long bone growth and increasing growth velocity, respectively.
Accordingly, instant claims 1-33 are anticipated by claims 1-33 of the ‘204 patent.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11911446 (hereinafter “the ‘446 patent”).
Instant claims 1-15 are directed to a method of treating skeletal dysplasia comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7; claim 2 recites the limitation that the treatment results in an improvement of increased absolute growth, and increased long-bone growth. Claims 16-22 are directed to a method of increasing long bone growth comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7. Claim 23-33 are directed to a method of increasing growth velocity comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7.
Claims 1-8 of the ‘446 patent are drawn to a method of increasing long bone growth in a subject comprising the step of administering to said subject a composition comprising (a) a CNP variant selected from the group consisting of SEQ ID NOs:1-7 and an amount of at least 7.5 µg/kg and (b) citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80, wherein said step of administering increases long bone growth in said subject. Claim 2 of the ‘446 patent recites that the subject has achondroplasia.
Claims 9-27 of the ‘446 patent are drawn to a method of increasing growth velocity in a subject comprising the step of administering to said subject a composition comprising (a) a CNP variant selected from the group consisting of SEQ ID NOs:1-7 and an amount of at least 7.5 µg/kg and (b) citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80, wherein said step of administering increases growth velocity in said subject. Claim 10 of the ‘446 patent recites that the subject has achondroplasia.
Dependent claims recite overlapping dosing concentrations and regimens, routes of administration, patient assessment parameters, and excipients/concentrations, as instantly claimed.
Accordingly, instant claims 1-33 are rendered obvious by claims 1-27 of the ‘446 patent.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12514906 (hereinafter “the ‘906 patent”).
Instant claims 1-15 are directed to a method of treating skeletal dysplasia comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7; claim 2 recites the limitation that the treatment results in an improvement of increased absolute growth, and increased long-bone growth. Claims 16-22 are directed to a method of increasing long bone growth comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7. Claim 23-33 are directed to a method of increasing growth velocity comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7.
Claim 1 of the ‘906 patent are drawn to a kit comprising a composition comprising a CNP variant peptide selected from the group consisting of SEQ ID NOs:1-7, wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80, and wherein the composition is lyophilized in a vial; and instructions for use.
Claims 2-14 of the ‘906 patent are drawn to a method of treating skeletal dysplasia in a subject comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein said CNP variant peptide is selected from the group consisting of SEQ ID NOs:1-7, wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80; wherein said composition comprises about 0.5 mg/ml to about 2.0 mg/ml of said CNP peptide variant; and wherein said step of administering treats said skeletal dysplasia in said subject. Claim 4 of the ‘906 patent recites that the subject has achondroplasia.
Claim 14 of the ‘906 patent is drawn to a method of increasing long bone growth in a subject in need thereof, said method comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein said CNP variant peptide is selected from the group consisting of SEQ ID NOIs:1-7, and wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80; wherein said composition comprises about 0.5 mg/ml to about 2.0 mg/ml of said CNP peptide variant.
Claim 15 of the ‘906 patent is drawn to a method of increasing growth velocity in a subject in need thereof, said method comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein said CNP variant peptide is selected from the group consisting of SEQ ID NOIs:1-7, and wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80; wherein said composition comprises about 0.5 mg/ml to about 2.0 mg/ml of said CNP peptide variant.
Claim 19 of the ‘906 patent are drawn to a method of treating skeletal dysplasia in a subject comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein said CNP variant peptide is selected from the group consisting of SEQ ID NOs:1-7, wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80; wherein said composition comprises about 10.0 mg/ml±9.9 mg/ml of said CNP peptide variant; and wherein said step of administering treats said skeletal dysplasia in said subject.
Dependent claims recite overlapping dosing concentrations and regimens, routes of administration, patient assessment parameters, and excipients/concentrations, as instantly claimed.
Accordingly, instant claims 1-33 are rendered obvious by claims 1-19 of the ‘906 patent.
Claims 1-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 12076372 (hereinafter “the ‘372 patent”).
Instant claims 1-15 are directed to a method of treating skeletal dysplasia comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7; claim 2 recites the limitation that the treatment results in an improvement of increased absolute growth, and increased long-bone growth. Claims 16-22 are directed to a method of increasing long bone growth comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7. Claim 23-33 are directed to a method of increasing growth velocity comprising administration of a composition comprising a CNP variant in an amount of at least 7.5 μg/kg, wherein the variant is selected from the group consisting of SEQ ID NOs:1-7.
Claims 1-11 of the ‘372 patent are drawn to a method of treating hypochondroplasia in a subject in need thereof comprising the step of administering to said subject a composition comprising a C-type natriuretic peptide (CNP) variant in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein the CNP variant is selected from the group consisting of SEQ ID NOS:1-7, wherein the CNP variant is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80 and wherein the step of administering treats said hypochondroplasia.
Claim 12 of the ‘372 patent is drawn to a method of increasing long bone growth in a subject in need thereof comprising the step of administering to said subject a composition comprising a C-type natriuretic peptide (CNP) variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein the CNP variant peptide is selected from the group consisting of SEQ ID NOS:1-7, wherein the CNP variant is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80 and wherein said step of administering increases long bone growth in said subject.
Claims 13-16 of the ‘372 patent are drawn to a method of increasing growth velocity in a subject in need thereof, said method comprising the step of administering a composition comprising a C-type natriuretic peptide (CNP) variant peptide to said subject in an amount of at least 7.5 μg/kg, wherein said CNP variant peptide is selected from the group consisting of SEQ ID NOS:1-7, wherein the CNP variant is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80 and wherein the step of administering increases growth velocity in said subject.
Dependent claims recite overlapping dosing concentrations and regimens, routes of administration, patient assessment parameters, and excipients/concentrations, as instantly claimed.
Accordingly, instant claims 1-33 are rendered obvious by claims 1-16 of the ‘372 patent.
Double Patenting / 101 rejection
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1-33 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-33 of copending Application No. 19407862 (hereinafter referred to as “the ‘862 application”). The instant claims are recited verbatim in claims 1-33 of the ‘862 application. This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Conclusion
No claims are allowed.
Claims 1-33 are pending and rejected.
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/KRISTINA M HELLMAN/ Examiner, Art Unit 1654
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