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 .
DETAILED ACTION
Status of Application, Amendments, and/or Claims
The Information Disclosure Statement (IDS) filed 2 April 2025 has been entered. Applicants’ submission of the replacement drawings filed 12 July 2024 is acknowledged. Applicants’ submission of a substitute specification filed 12 July 2024 is acknowledged.
Election/Restriction
In the response received on 16 March 2026, Applicants elected the species of: A) wherein the disorder to be treated is osteoporosis: and B) wherein the sclerostin antibody is romosozumab.
Claims 16-19 and 21-40 are cancelled. Claims 1-15 and 20 are pending and under examination to the extent they read on the elected species.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities:
The substitute specification filed 12 July 2024 does not incorporate the amendment of the specification filed 20 November 2023.
The tile of the specification is different from that in the Application Data Sheet.
Appropriate correction is required.
Claim Objections
The following claims are objected to because of the informalities:
In claim 1, the phrase “which are lower than the initial loading dose of (a)” should be “which are lower than the initial loading dose or doses of (a)”.
In claim 2, “the doses of (b)” should be “the dose(s) of (b)”.
In claim 3, “the initial loading dose or dose(s)” should be “the initial loading dose or doses”. Also, “(i)” should be deleted because there is no “(ii)”; and a semicolon “;” is missing at the end of line (i).
In claim 4, “the initial dose is from 7 mg/kg to 50 mg/kg (or from 15 mg/kg to 30 mg/kg)” should be “the initial dose(s) of (a) is/are from 7 mg/kg to 50 mg/kg (or from 15 mg/kg to 30 mg/kg)”.
In claim 5 (i), “the batch of doses includes the dose(s) of (a) and (b)” should be “the batch of doses includes the dose(s) of (a) and the dose(s) of (b)”.
In claims 10, 12, 15 and 20, “where …” should be “wherein …”.
In claim 12, the phrase “the subject: (i) has been diagnosed with a bone disorder and the method is the first treatment for the disorder…” should be “the subject: (i) has been diagnosed with the bone disorder and the method is the first treatment for the bone disorder”.
Claim 13 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. See MPEP § 608.01(n). Accordingly, the claim has not been further treated on the merits.
Claim 13 has typographical errors, e.g., “1 x 10’ M”, “IC5O”, and “IC5O”; also, the phrase “in HEK293 cell lines” should be “in a HEK293 cell line” or “in HEK293 cells”.
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 1-6, 9, 13 and 20 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 pre-AIA the applicant regards as the invention.
Claims 1-6, 9 and 20 refer to “(a)” and/or “(b)”, however, the claims do not have steps set forth as “(a)” and “(b)”.
Claim 3 recites “at least three to seven times higher than the dose(s) of (b)”. The claim is indefinite in the recitation of the dose range because “at least” has no upper limit. It is unclear whether the dose or doses are limited between three to seven times higher than the dose(s) of (b).
Claim 5 recites “(iii) administering to the subject at least one further dose of sclerostin antibody after the dosing holiday of (b).” In the previous claims, “(b)” appears to refer to a batch of dose(s), not a dosing holiday.
Claims 13 recite: “when there is less than a 6-fold excess of moles of sclerostin binding sites per well as compared to the number of moles of sclerostin per well”. The metes and bounds of the claim are unclear. In addition, the phrase “such as a bone specific alkaline phosphatase assay” renders the claim indefinite because it is unclear whether the limitation following the phrase "such as" part of the claimed invention. See MPEP § 2173.05(d).
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 1-3, 5-6, 10-14 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kneissel et al. (WO 2009/047356 A1, Int’l. Pub. Date: 16 April 2009).
Kneissel teaches a method for treating a bone disorder, such as osteoporosis (which increases a risk of a bone fracture), in a subject, comprising administering to the subject a pharmaceutical composition comprising an antibody direct against sclerostin (see, for example, claims 37 and 38). Kneissel teaches that the dosage regimens are adjusted to provide the optimum desired response (e.g., a therapeutic response); for example, a single bolus may be administered, several divided doses may be administered over time, and the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation (p. 46, 2nd paragraph). Kneissel teaches that the dosage can be 0.3 mg/kg body weight, 1 mg/kg body weight, 3 mg/kg body weight, 5 mg/kg body weight, 10 mg/kg body weight, or within the range of 1-10 mg/kg body weight; treatment regime entails administration once per week, once every two weeks, once every three weeks, once every four weeks, once a month, once every 3 months, or once every 3 to 6 months (p. 46, 3rd paragraph). Kneissel teaches exemplified dosage regimens, e.g., the antibody being given every four weeks for six dosages, then every three months; 3 mg/kg body weight once followed by 1 mg/kg body weight (p. 46, 3rd paragraph). From the batch of doses given every four weeks to the batch of doses given every three months, there is a “dosing holiday” at least four weeks in length. Therefore, Kneissel meets the limitation “allowing the subject a dosing holiday of at least four weeks after the batch of doses of (a) and (b)”, as recited in claim 5. Regarding claim 6, which recites “after at least one of the dose(s) of (b) monitoring the subject to identify whether the subject shows a reduced response to a dose of the sclerostin antibody and, where such a reduced response is identified, allowing the subject a dosing holiday which is at least four weeks in length”, the “monitoring” step herein reads on a mental step. Further, according to the instant specification (under section “Responses and Monitoring” at p. 24), whether or not a response can be considered reduced may be defined by whether the response of the bone marker to administration of the anti-sclerostin antibody is reduced; and the response in question may also be defined by reference to bone mineral density (BMD) or bone mineral content (BMC). In some cases, it may be that the reduced response is a reduced rate of increase of BMD and/or BMC following administration of the antibody. Therefore, the specification indicates that administration of the antibody still results in an increase in bone formation and/or a reduction of bone absorption, for example, in terms of BMD/BMC, but at a reduced rate compared to a naive subject. Based on the instant specification, Kneissel meets this limitation of “monitoring the subject to identify whether the subject shows a reduced response to a dose of the sclerostin antibody”. Kneissel further shows that the antibody (e.g., MOR05813) neutralized human sclerostin in a cell-based Wnt signaling assay in HEK293 cells (Example 6).
Therefore, Kneissel anticipates the instant claims.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 4 and 7-9 are further rejected under 35 U.S.C. 103 as being unpatentable over Kneissel et al. (WO 2009/047356 A1).
Kneissel teaches as set forth above. Kneissel, however, does not teach the initial loading dose in a range as recited in claim 4, nor teaches administering a different drug, which is an anti-resorptive, optionally a biophosphonate, to treat the bone disorder during the dosing holiday (claims 7-9).
Kneissel teaches administering the sclerostin antibody in a dose range of 1-10 mg/kg, e.g., 5 mg/kg; and Kneissel teaches using a higher initial dose followed by a lower subsequent dose(s), e.g., with an initial dose of 3 mg/kg followed by 1 mg/kg subsequent dose(s). Kneissel also teaches combining the sclerostin antibody with alternative therapies for treating osteoporosis, such as bisphosphonates (p. 3, 5th paragraph). Kneissel teaches that when the sclerostin antibody is administered together with another agent, the two can be administered in either order, i.e., sequentially (p. 50, 3rd full paragraph).
Given that the level of skill in this art is very high, and that optimizing parameters, such as the dosage of a therapeutic agent, is routine, modifying the initial dose used in Kneissel’s treatment method to the claimed ranges would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, with a reasonable expectation of success, absent evidence of unexpected results. As was found in In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), where the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Further, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Kneissel to administer an alternative therapy for treating osteoporosis, such as a bisphosphonate, during the interval of doses of the sclerostin antibody, for example, between doses given every three months. One of ordinary skill in the art would have been motivated to do so, because Kneissel teaches a method for treating a bone disorder, such as osteoporosis, in a subject, comprising administering to the subject multiple doses of an anti-sclerostin antibody, given every four weeks and then every three months, and the treatment may be in combination with an alternative therapy, such as a bisphosphonate, which is given sequentially with the sclerostin antibody. It provides a reasonable expectation of success in treating the patients.
Claim 15 is further rejected under 35 U.S.C. 103 as being unpatentable over Kneissel et al. (WO 2009/047356 A1), as applied to claims 1-3, 5-6, 10-14 and 20 above, and further in view of Padhi et al. (US 2009/0074763 A1, Pub. Date: Mar. 19, 2009).
Kneissel teaches as set forth above. Kneissel, however, does not teach using an anti-sclerostin antibody as recited in claim 15.
Padhi teaches anti-sclerostin antibodies useful for treating bone-related disorders, such as osteoporosis. Padhi teaches that an anti-sclerostin antibody that has a binding affinity less than or equal to 1x10-7 M, that binds to the sequence of SEQ ID NO: 6, that cross-blocks the binding of Ab-5 to sclerostin or is cross-blocked from binding to sclerostin by Ab-5, or that comprises the amino acid sequences of the CDRs, the heavy and light chains as recited in the present claims (see claims of the ‘763 application).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the anti-sclerostin antibodies taught by Padhi in the treatment method of Kneissel. One of ordinary skill in the art would have been motivated to do so, because Kneissel teaches a method for treating a bone disorder, such as osteoporosis, in a subject, comprising administering to the subject a pharmaceutical composition comprising an antibody direct against sclerostin, and Padhi further teaches anti-sclerostin antibodies useful for treating bone-related disorders, such as osteoporosis. Therefore, the combined teachings provide a reasonable expectation of success in treating the patients.
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 1-15 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No: 11,851,483.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the ‘483 patent recites: “A method for increasing at least one of bone formation, bone mineral density, bone mineral content, bone mass, bone quality and bone strength in a mammalian subject in need thereof, which method comprises: (a) administering at least two initial doses of sclerostin antibody to a subject in need of such treatment, wherein the initial doses are administered every month or every four weeks, and wherein the sclerostin antibody comprises a set of 6 CDRs set forth in SEQ ID NOs: 245-247 and SEQ ID NOs: 78-80; (b) administering further doses of sclerostin antibody to the subject, wherein each of the further doses is at least 210 mg, wherein the further doses are administered once every two months or once every four months, and wherein together (a) and (b) comprise administering a batch of doses comprising at least twelve doses of sclerostin antibody; (c) allowing a dosing holiday that is at least two times greater than the length of the interval between the doses in (b); and (d) administering to the subject at least one further dose of sclerostin antibody after the dosing holiday of (c).” Depending claims further limit wherein the doses of (a) comprise an initial loading dose and either the further doses of (a) or those of (b) comprise doses which are lower than the initial loading dose. The essential features of the instant claims are present in the claims of the ‘483 patent. Therefore, the claims of the ‘483 patent anticipate the instant claims.
Conclusion
NO CLAIM IS ALLOWED.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOZHEN XIE/Primary Examiner, Art Unit 1674