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 .
Priority
Applicant’s claim for the benefit of foreign priority under 35 U.S.C. 119 (a)-(d)is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed applications, Application Nos. EP16191454.4, EP17155846.3, PCT/EP2017/074594, 16/337,955, and 18/053,701 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Application Nos. EP16191454.4, EP17155846.3, PCT/EP2017/074594, 16/337,955, and 18/053,701 fail to provide written description and enablement for claims 1-7 and 17-18 for at least the same reasons presented in the rejections under 35 U.S.C. § 112 below. Therefore, Application Nos. EP16191454.4, EP17155846.3, PCT/EP2017/074594, 16/337,955, and 18/053,701 cannot be used to overcome prior art rejections. The earliest effective filing date of claims 1-7 and 17-18 is the filing date of the instant application, October 27, 2023.
Claim Rejections - 35 USC § 112
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.
Issues Relevant to Both Written Description and Enablement Presented Once for Brevity
1) Scope of the Claims
The claims are drawn to a method of treating a human patient having hypoparathyroidism comprising administering a pharmaceutical composition comprising a PTH compound, wherein the PTH compound exhibits a peak to trough ratio of less than four within one administration interval.
The PTH compound is of formula (Ia) or (Ib) which comprise a PTH moiety (D) connected to a water-soluble carrier moiety (Z) via a reversible prodrug linker moiety (L1) and a chemical bond or spacer moiety (L2).
The specification defines the term "PTH" on page 5 as follows: “all PTH polypeptides, preferably from mammalian species, more preferably from human and mammalian species, more preferably from human and murine species, as well as their variants, analogs, orthologs, homologs, and derivatives and fragments thereof, that are characterized by raising serum calcium and renal phosphorus WO 2018/060312 PCT/EP2017/074594excretion, and lowering serum phosphorus and renal calcium excretion. The term "PTH" also refers to all PTH-related polypeptides (PTHrP), such as the polypeptide of SEQ ID NO: 121, that bind to and activate the common PTH/PTHrP 1 receptor. Preferably, the term "PTH" refers to the PTH polypeptide of SEQ ID NO:51 as well as its variants, homologs and5 derivatives exhibiting essentially the same biological activity, i.e. raising serum calcium and renal phosphorus excretion, and lowering serum phosphorus and renal calcium excretion.”
The other compounds of the PTH compound, the water-soluble carrier moiety (Z), reversible prodrug linker moiety (L1) and a chemical bond or spacer moiety (L2), are defined functionally, not structurally.
In addition to the structure and activity of the PTH compound, the scope of the claim is defined by the functional limitation pertaining to the pharmacokinetic profile. The specification defines the claim term “peak to trough ratio” on page 5 as follows: “the ratio between the highest plasma concentration and the lowest plasma concentration of the PTH compound at steady state.” The specification defines the term “steady state” on page 4 as follows: “a state achieved after a multitude of constant doses, such as after 3, 4, 5, 6, 7 or more constant doses, of a medicament have been administered to a patient with constant time intervals between two consecutive administration, which state is characterized in that the plasma levels of the PTH compound, if the PTH compound does not release PTH, i.e. is a stable PTH compound, or of released PTH, if the PTH compound is a controlled-release PTH compound, at the beginning and at the end of an interval vary by no more than 10%, preferably by no more than 7.5%, even more preferably by no more than 5%, even more preferably by no more than 4% and most preferably by no more than 3%.”
2) Actual reduction to practice/Working examples
The instant specification includes a limited reduction to practice: Examples 27 and 28 present a pharmacokinetic study of transient 2x20 kDa S1 PEG conjugate 18 in cynomolgus monkeys and Example 29 presents the same in Sprague-Dawley rats. The PTH compound exhibited a low peak-to-trough ratio of below three.
3) Predictability in the art
There is a large body of work in the pharmacokinetic art and yet there is a high level of unpredictability and complexity associated with modulating parameters such as peak-to-trough ratio, as evidenced by Smith et al. (“Relevance of Half-Life in Drug Design,” J. Med. Chem. 2018, 61, 4273−4282). The prior art does not present clear rules to distinguish PTH compositions that exhibit a peak-to-trough ratio less than four from those that do not. Even the prior art that discloses a related prodrug formula, WO 2009/095479 A2, reports widely varying in vitro release kinetics depending on the structure of the prodrug. Example 51 of WO 2009/095479 A2 presents release half-times ranging from less than 3 minutes to 58 days, depending on the structure of the conjugate. This data pertains to GLP conjugates but the point remains that varying the structure of the conjugate leads to variation in in vitro release kinetics in unpredictable ways.
In addition, the prior art recognizes the unpredictability associated with the use of a PTH compound to treat hypoparathyroidism. In a review by Cusano et al. (“Use of parathyroid hormone in hypoparathyroidism,” J Endocrinol Invest. 2013 Dec; 36(11): 1121–1127), the authors note that “Hypoparathyroidism is the only classic endocrine deficiency disease for which the missing hormone, PTH, is not yet an approved treatment.” Cusano et al. report that the complicated effects of PTH compounds on calcium, vitamin D requirements, bone-remodeling dynamics and bone metabolism and the chronic nature of hypoparathyroidism necessitate further studies to determine safety of PTH compounds for hypoparathyroidism patients (abstract).
4) Guidance in the specification/Structure-function correlation
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the PTH activity or the pharmacokinetics and therefore do not describe which substitutions, deletions or additions could be made to the polypeptide, which structural changes could be made to the conjugate prodrug structure, or which changes could be made to the composition while preserving function and pharmacokinetics.
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the PTH amino acids, the conjugate structure and the composition components in determining peak-to-trough ratio are not described. As a result, it is impossible to predict, based on the specification, how changing any of these elements will affect the pharmacokinetics, specifically the peak-to-trough ratio.
Claims 1-7 and 17-18 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 claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Only one embodiment of the invention was reduced to practice. Examples 27 and 28 present a pharmacokinetic study of transient 2x20 kDa S1 PEG conjugate 18 in cynomolgus monkeys and Example 29 presents the same in Sprague-Dawley rats. The PTH compound exhibited a low peak-to-trough ratio of below three. As discussed above the claim scope is potentially enormous with respect to the PTH compound structure and the composition components; in comparison, the scope of the description which only includes one species, is extremely narrow. The actual reduction to practice does not include species with different conjugate linkers, different polymers or different PTH sequences. One of ordinary skill in the art would not consider transient 2x20 kDa S1 PEG conjugate 18 to be representative of the full scope of the claimed genus. As a result, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone. Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
The specification also fails to disclose the physical basis for the claimed PTH activity and pharmacokinetics, and to disclose a structure-function correlation. Understanding the physical basis for the claimed activity is critical to determining which of the sequences, carrier structures, and linker structures that meet the structural requirements of the genus also meet the functional requirements of the genus.
As described above there is a high degree of unpredictability in the prior art with respect to PTH structure-function, PTH administration, the effect of conjugate structure on pharmacokinetics, and the use of PTH to treat hypoparathyroidism. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless PTH compounds that meet the structural requirements of the claims would also be able to meet the complicated claimed functions. The specification does not make clear which PTH compounds are in the genus and which are not because it does not describe the physical basis for the claimed activity. In other words, the specification does not describe which peptides to make.
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention. In conclusion, only a method of treating hypothyroidism with transient 2x20 kDa S1 PEG conjugate 18 meets the written description provision of 35 U.S.C. 112(a).
Claims 1-7 and 17-18 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 treating hypoparathyroidism with transient 2x20 kDa S1 PEG conjugate 18 does not reasonably provide enablement for the use of any other PTH compounds having a peak to trough ratio of less than 4. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Factors (2)-(8) are discussed above.
The scope of the claimed compositions of formula (Ia) and (Ib) is extremely broad relative to the narrow reduction to practice in the specification. That fact combined with the level of unpredictability and complexity in the art, the relative skill in the art, and the lack of specific guidance in the specification, poses an undue burden of experimentation on one of ordinary skill in the art seeking to practice the claimed methods. The specification is an invitation to undertake a research program to identify additional compositions that could be used to carry out different embodiments of the claims. As such, the specification fails to meet the enablement provision of 35 U.S.C. 112(a).
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 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.
Claims 1-7 and 17-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2017/148883 A1 (published September 8, 2017)1.
WO 2017/148883 A1 teaches a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising the PTH compound:
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(p. 3, lines 27 - p. 4, line 16; Example 18, conjugate 18). The compound is a compound of formula (Ia) wherein D is a PTH moiety consisting of SEQ ID NO: 51 and wherein the structure corresponds to the claimed formula as follows:
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The prior art PTH compound meets the functional limitations of instant claim 1, as evidenced by the fact that the compound is identical to the compound reduced to practice in the instant specification (conjugate 18, Examples 18, 23 and 27) that exhibits a low peak-to-trough ratio of below 3 (i.e. less than 4) in plasma within one injection interval at steady state after daily subcutaneous injection. WO 2017/148883 A1 also reports a low peak-to-trough ratio of below 3 (i.e. less than 4) in plasma within one injection interval at steady state after daily subcutaneous injection (Example 27) and that the compound is controlled-release with a release half life time of 2.8 days (Example 23).
Therefore, a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising conjugate 18 taught by WO 2017/148883 A1 meets all of the limitations of instant claims 1 and 7.
With respect to claims 2-4, WO 2017/148883 A1 teaches that the time period between two consecutive subcutaneous administrations is 24 hours (e.g. daily) (Example 27) or one week (p. 88, line 33 - p. 89, line 24).
With respect to claims 5-6, WO 2017/148883 A1 teaches administration via subcutaneous injection with a pen device (p. 93, line 9).
With respect to claims 17-18, WO 2017/148883 A1 teaches that the pharmaceutical composition comprising the PTH compound has a pH ranging from 3 to 8, preferably 4 to 5 (p. 90, lines 1-5).
Claims 1-7 and 17-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018/060310 A1 (published April 5, 2018).2
WO 2018/060310 A1 teaches a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising the PTH compound:
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(Example 22; Example 18, conjugate 18). The compound is a compound of formula (Ia) wherein D is a PTH moiety consisting of SEQ ID NO: 51 and wherein the structure corresponds to the claimed formula as follows:
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Because the prior art teaches a composition that meets all of the structural and physical limitations of the claim, the claimed property regarding peak to trough ratio is inherent to the prior art composition and method. Inherency is further evidenced by the fact that the compound is identical to the compound reduced to practice in the instant specification (conjugate 18, Examples 18, 23 and 27) that exhibits a low peak-to-trough ratio of below 3 (i.e. less than 4) in plasma within one injection interval at steady state after daily subcutaneous injection. Therefore, a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising conjugate 18 taught by WO 2018/060310 A1meets all of the limitations of instant claims 1 and 7.
With respect to claims 2-4, WO 2018/060310 A1 teaches that the time period between two consecutive subcutaneous administrations is 24 hours (e.g. daily) (p. 39, lines 25-26) or one week (p. 40, lines 10-11).
With respect to claims 5-6, WO 2018/060310 A1 teaches administration via subcutaneous injection with a pen device (p. 41, line 6).
With respect to claims 17-18, WO 2018/060310 A1 teaches that the pharmaceutical composition comprising the PTH compound has a pH 4 (Example 22).
Claims 1-7 and 17-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018/060311 A1 (published April 5, 2018).3
WO 2018/060310 A1 teaches a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising the PTH compound:
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(p. 3-4; Example 18, conjugate 18). The compound is a compound of formula (Ia) wherein D is a PTH moiety consisting of SEQ ID NO: 51 and wherein the structure corresponds to the claimed formula as follows:
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Because the prior art teaches a composition that meets all of the structural and physical limitations of the claim, the claimed property regarding peak to trough ratio is inherent to the prior art composition and method. Inherency is further evidenced by the fact that the compound is identical to the compound reduced to practice in the instant specification (conjugate 18, Examples 18, 23 and 27) that exhibits a low peak-to-trough ratio of below 3 (i.e. less than 4) in plasma within one injection interval at steady state after daily subcutaneous injection. Therefore, a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising conjugate 18 taught by WO 2018/060311 A1 meets all of the limitations of instant claims 1 and 7.
With respect to claims 2-4, WO 2018/060311 A1 teaches that the time period between two consecutive subcutaneous administrations is 24 hours (e.g. daily) (p. 38, lines 10-11) or one week (p. 38, lines 29-30).
With respect to claims 5-6, WO 2018/060311 A1 teaches administration via subcutaneous injection with a pen device (p. 39, line 3).
With respect to claims 17-18, WO 2018/060311 A1 teaches that the pharmaceutical composition comprising the PTH compound has a pH 4-5 (p. 93, lines 1-2).
Claims 1-7 and 17-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2020/165087 A1 (published August 20, 2020).4
WO 2020/165087 A1 teaches a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising the PTH compound:
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(p. 104-105; Example 1, conjugate 18). The compound is a compound of formula (Ia) wherein D is a PTH moiety consisting of SEQ ID NO: 51 and wherein the structure corresponds to the claimed formula as follows:
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Because the prior art teaches a composition that meets all of the structural and physical limitations of the claim, the claimed property regarding peak to trough ratio is inherent to the prior art composition and method. Inherency is further evidenced by the fact that the compound is identical to the compound reduced to practice in the instant specification (conjugate 18, Examples 18, 23 and 27) that exhibits a low peak-to-trough ratio of below 3 (i.e. less than 4) in plasma within one injection interval at steady state after daily subcutaneous injection. Therefore, a method of treating hypoparathyroidism comprising administering a pharmaceutical composition comprising conjugate 18 taught by WO 2020/165087 A1 meets all of the limitations of instant claims 1 and 7.
With respect to claims 2-4, WO 2020/165087 A1 teaches that the time period between two consecutive subcutaneous administrations is 24 hours (e.g. daily) (p. 110, line 6) or one week (p. 110, line 14).
With respect to claims 5-6, WO 2020/165087 A1 teaches administration via subcutaneous injection with a pen device (p. 109, line 31).
With respect to claims 17-18, WO 2020/165087 A1 teaches that the pharmaceutical composition comprising the PTH compound has a pH 4-5 (Table 1).
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
I. ODP rejections over parent applications
Claims 1-3, 5-7, and 17-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,759,504. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Reference claim 1 recites a pharmaceutical composition comprising a parathyroid hormone (PTH) compound, wherein the pharmaceutical composition is suitable for subcutaneous administration, and wherein after subcutaneous administration to a mammal the PTH compound has a pharmacokinetic profile exhibiting a peak to trough ratio of free PTH of less than 4 in plasma within one daily injection interval at steady state; wherein the PTH compound is a water-soluble controlled-release PTH compound of formula (Ia) or a pharmaceutically acceptable salt thereof Z-(L2-L1-D), wherein -D is a PTH moiety, which has the sequence of SEQ ID NO:51; -L2-L1- has the formula:
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wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond; and the dashed line marked with an asterisk indicates attachment to Z; Z comprises a polyethylene glycol polymer of about 40 kDa; x is 1; and the PTH moiety is released with a release half-life of at least 12 hours.
A claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use (Sun Pharmaceutical. Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010)). In the instant case, the reference patent discloses a method of treating hypoparathyroidism with the claimed composition (col 3). Therefore, claim 1 is not patentably distinct from the reference claim.
With respect to claims 2-3, reference claim 1 requires one daily injection.
Regarding claims 5-6, reference claim 3 requires that administration is subcutaneous injection with a pen device.
With respect to claim 7, reference claim 4 requires that the peak to trough ratio is less than 3.
Regarding claims 17-18, reference claim 8 requires that the pharmaceutical composition has a pH ranging from and including pH 4 to pH 5.
Claims 1-7 and 17-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,857,603. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claims.
Reference claim 1 recites method of treating a human patient having hypoparathyroidism comprising subcutaneously administering a pharmaceutical composition comprising a parathyroid hormone (PTH) compound, wherein the pharmacokinetic profile of the PTH compound exhibits a peak to trough ratio of less than 4 within one administration interval at a steady state; wherein the PTH compound is a water-soluble controlled-release PTH compound of formula (Ia) or a pharmaceutically acceptable salt thereof Z-(L2-L1-D), wherein -D is a PTH moiety, which has the sequence of SEQ ID NO:51; -L2-L1- has the formula:
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wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond; and the dashed line marked with an asterisk indicates attachment to Z; Z comprises a polyethylene glycol polymer of about 40 kDa; x is 1; and the PTH moiety is released with a release half-life of at least 12 hours.
A claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use (Sun Pharmaceutical. Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010)). In the instant case, the reference patent discloses a method of treating hypoparathyroidism with the claimed composition (col 3). Therefore, claim 1 is not patentably distinct from the reference claim.
With respect to claim 2, reference claim 2 requires that the administration interval is at least 24 hours.
With respect to claim 3, reference claim 3 requires that the administration interval is 24 hours.
With respect to claim 4, reference claim 3 requires that the administration interval is weekly.
Regarding claims 5-6, reference claim 3 requires that administration is subcutaneous injection with a pen device.
With respect to claim 7, reference claim 7 requires that the peak to trough ratio is less than 3.
Regarding claims 17-18, reference claim 9 requires that the pharmaceutical composition has a pH ranging from and including pH 4 to pH 5.
II. ODP over cases in the same family as prior art reference WO 2017/148883
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,793,861 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 9 recites a method of treating hypoparathyroidism with a PTH compound that is structurally identical to a PTH compound that falls within the genus of instant claims 1-7:
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which is a PTH moiety (D) linked to a polyethylene glycol polymer (Z) via a reversible linker (L1-L2).
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3 (claim 7).
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claims 2-3, reference claim 13 requires the pharmaceutical composition is administered once every 24 hours.
Regrading claim 4, reference claim 14 requires the pharmaceutical composition is administered once every week.
Regarding claims 5-6, reference claim 11 requires subcutaneous administration with a pen device.
Claims 1-7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,214,020 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 1 recites a method of treating hypoparathyroidism with a PTH compound that is structurally identical to a PTH compound that falls within the genus of instant claims 1-7:
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which is a PTH moiety (D) linked to a polyethylene glycol polymer (Z) via a reversible linker (L1-L2).
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3 (claim 7).
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claims 2-3, reference claim 5 requires the pharmaceutical composition is administered once every 24 hours.
Regrading claim 4, reference claim 6 requires the pharmaceutical composition is administered once every week.
Regarding claims 5-6, reference claim 3 requires subcutaneous administration with a pen device.
III. ODP rejections over cases in the same family as prior art reference WO 2018/060310
Claims 1 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,590,207 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims anticipate the instant claims.
Reference claim 1 recites a method of treating hypoparathyroidism comprising administering a PTH compound that is structurally identical to a PTH compound that falls within the genus of instant claims 1:
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(L1-L2) wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond to a PTH moiety of SEQ ID NO: 51 (D); and the dashed line marked with an asterisk indicates attachment to a polyethylene glycol polymer (Z). Reference claim 1 requires subcutaneous administration every 24 hours, satisfying all of the structural limitations of claims 1-3 and 5. With respect to claims 17-18, reference claim 3 requires pH 3 to 8, which is the same as the range in claim 17 and which overlaps with the range in claim 18.
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3.
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Claims 1, 7, and 17-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,890,326 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 1 recites a PTH compound that is structurally identical to a PTH compound that falls within the genus of instant claims 1, 7, and 17-18:
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(L1-L2) wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond to a PTH moiety of SEQ ID NO: 51 (D); and the dashed line marked with an asterisk indicates attachment to a polyethylene glycol polymer (Z). The reference claims do not recite a method of treating hypoparathyroidism.
A claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use (Sun Pharmaceutical. Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010)). In the instant case, the reference patent discloses a method of treating hypoparathyroidism throughout the specification.
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3.
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Reference claim 6 requires pH 4 to 6, which falls within and overlaps with the range of claims 17 and 18, respectively.
Claims 1 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,918,628 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 1 recites a PTH compound that is structurally identical to a PTH compound that falls within the genus of instant claims 1, 7, and 17-18:
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(L1-L2) wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond to a PTH moiety of SEQ ID NO: 51 (D); and the dashed line marked with an asterisk indicates attachment to a polyethylene glycol polymer (Z). The reference claims do not recite a method of treating hypoparathyroidism.
A claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use (Sun Pharmaceutical. Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010)). In the instant case, the reference patent discloses a method of treating hypoparathyroidism throughout the specification.
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3.
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Claims 1-3, 5-7, and 17-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 12,295,989 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 1 recites a method of treating or controlling hypoparathyroidism in a human patient, comprising the step of administering to the human patient a pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt thereof by subcutaneous injection no more frequently than once every 24 hours, wherein the PTH compound falls within the genus of instant claims 1-3, 5-7, and 17-18:
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(L1-L2) wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond to a PTH moiety of SEQ ID NO: 51 (D); and the dashed line marked with an asterisk indicates attachment to a polyethylene glycol polymer (Z).
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3.
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claims 2-3, reference claim 2 requires the pharmaceutical composition is administered once every 24 hours.
Regarding claims 5-6, reference claim 3 requires subcutaneous administration with a pen device.
Regarding claims 17-18, reference claim 5 requires pH3-8, which is the same as and overlaps with the claimed ranges, respectively.
Claims 1-3, 5-7, and 17-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-17, 21-22, and 28 of copending Application No. 19/077,517 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claim 1 recites a method of treating or controlling hypoparathyroidism in a human patient, comprising the step of administering to the human patient a pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt thereof by subcutaneous injection no more frequently than once every 24 hours, wherein the PTH compound falls within the genus of instant claims 1-3, 5-7, and 17-18:
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(L1-L2) wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond to a PTH moiety of SEQ ID NO: 51 (D); and the dashed line marked with an asterisk indicates attachment to a polyethylene glycol polymer (Z).
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3.
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claims 2-3, reference claim 17 requires the pharmaceutical composition is administered once every 24 hours.
Regarding claims 5-6, reference claim 21 requires subcutaneous administration with a pen device.
Regarding claims 17-18, reference claim 28 requires pH 3-8, which is the same as and overlaps with the claimed ranges, respectively.
IV. ODP rejections over cases in the same family as prior art reference WO 2020/165087
Claims 1 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,403,182 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 6 recites a method of treating hypoparathyroidism with a PTH compound that is structurally identical to a PTH compound that falls within the genus of instant claims 1 and 7:
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(L1-L2) wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond to a PTH moiety of SEQ ID NO: 51 (D); and the dashed line marked with an asterisk indicates attachment to a polyethylene glycol polymer (Z).
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3 (claim 7).
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Claims 1, 7, and 17-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6, 8, 10-11, 13-14, 16-24, 28, 30, 34, 36, 43, and 45 of copending Application No. 19/279,831 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claims 45 and 19 recite a method of treating hypoparathyroidism with a PTH compound that is structurally identical to a PTH compound of Formula (Ia) and (Ib)
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3 (claim 7).
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claims 17-18, reference claims 17-18 require pH 3-6, which falls within and overlaps with the claimed ranges, respectively.
V. ODP rejections over cases in the same family as prior art reference WO 2018/060311
Claims 1-3, 5, and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,453,778 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other.
Reference claim 1 recites a method of treating hypoparathyroidism with a PTH compound that is structurally identical to a PTH compound that falls within the genus of instant claims 1-3, 5, and 7:
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(L1-L2) wherein the unmarked dashed line indicates the attachment to a nitrogen of -D by an amide bond to a PTH moiety of SEQ ID NO: 51 (D); and the dashed line marked with an asterisk indicates attachment to a polyethylene glycol polymer (Z).
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3 (claim 7).
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claims 2-3, reference claim 3 requires the pharmaceutical composition is administered once every 24 hours.
Regarding claim 5, reference claim 4 requires subcutaneous administration.
Claims 1-3, 5, and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 19/354,691 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claims 16 and 14 recite a method of treating hypoparathyroidism with a PTH compound that is structurally identical to a PTH compound of Formula (Ia) and (Ib)
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3 (claim 7).
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claims 2-3, reference claims 6-7 requires the pharmaceutical composition is administered once every 24 hours.
Regarding claim 5, reference claim 8 requires subcutaneous administration.
V. ODP rejections over cases with no corresponding prior art
Claims 1, 5, and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 19/396,182 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claims 7-8, 10, and 15-17 recite a method of treating hypoparathyroidism with a PTH compound that is structurally identical to a PTH compound of Formula (Ia) and (Ib) wherein Z is a PEG-based polymer.
The reference claims are silent with respect to the pharmacokinetic profile limitations of the instant claims 1 and 7. Specifically, the reference claims are silent with respect to the peak to trough ratio of less than 4 (claim 1), and the peak to trough ratio of less than 3 (claim 7).
MPEP §§ 2112 - 2112.02 states that a rejection is proper when the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, the basis for shifting burden of proof to applicant is that reference claim compositions meet all of the structural and physical limitations of the instant claims. If the all of the functional limitations are also met, the claims are anticipated.
Regarding claim 5, reference claim 9 requires subcutaneous administration.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached on Monday-Friday, 7 am - 3 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
1 WO 2017/148883 A1 is in the same patent family as US 11,793,861 and US 12,214,020, which are the subject of nonstatutory double patenting rejections below.
2 WO 2018/060310 A1 is in the same patent family as US 11,590,207, US 11,890,326, US 11,918,628, US 12,295,989 and Application No. 19/077,517, which are the subject of nonstatutory double patenting rejections below.
3 WO 2018/060311 A1 is in the same patent family as US 12,453,778 and Application No. 19/354,691, which are the subject of nonstatutory double patenting rejections below.
4 WO 2020/165087 A1 is in the same patent family as US 12,403,182 and Application No. 19/279,831, which are the subject of nonstatutory double patenting rejections below.
Prosecution Insights