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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-2, 4, 6, 11-12, 18-19, 21, 23, 26, and 28-29 in the reply filed on 6/18/2026 is acknowledged. Applicant canceled non-elected Group II, claims 14-14 and 31 in response to restriction requirement.
In response to species election, applicant elected (a) the pharmaceutical composition of species (i), (b) a buffer of succinate, and (c) a tonicity modifier of sodium chloride.
Claim Status
Claims 1-2, 4, 6, 8-9, 11-12, 18-19, 21, 23, 26, and 28-29 are pending.
Claims 3, 5, 7, 10, 13-17, 20, 22,24-25, 27, and 30-31 are cancelled.
Claims 18-19, 21, 23, 26, and 28-29 are withdrawn as being directed to a non-elected species, the election having been made on 6/18/2026 without traverse.
Claims 1-2, 4, 6, 8-9, 11-12 have been examined.
Priority
This application is a 371 of PCT/US22/27451 filed on 05/03/2022
PCT/US22/27451 has PRO 63/184,924 filed on 05/06/2021
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/26/2023 and 6/18/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 6 and 23 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.
Triton X-100 is a registered trademark currently owned by The Dow Chemical Company (or its affiliated companies), and
Pluronic is a registered trademark of the BASF Corporation.
It is important to recognize that a trademark is used to identify a source of goods, and not the goods themselves. Thus, a trademark does not identify or describe the goods associated with the trademark. See definitions of trademark in MPEP § 608.01(v). If the trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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.
Claims 1-2, 4, 6, 8-9, 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Maclean et al. (WO 2014/210489 A1, cited in IDS) in view of Mahler et al. (J Pharm Sci. 2010 Jun;99(6):2620-7.10).
Claim 1 is drawn to a pharmaceutical formulation at pH of 2 to 5 comprising (i) etelcalcetide or salt thereof and (ii) a surfactant in aqueous solution.
Maclean et al. teach a liquid formulation of AMG 416 (synonym of Etelcalcetide as defined in the instant SPEC [0016]). Maclean et al. teach the pH of etelcalcetide formulation has a pH of 3.0 to 3.5 to 3.0 to 4.0 (p2, line 20-21). Maclean et al. teach the use of succinate buffers, acetate buffers, citrate buffers or phosphate buffers to achieve a desired pH (p2, 23-27), reading on the limitation (i) of a pharmaceutical formulation at pH of 2 to 5 comprising etelcalcetide. Maclean et al. further teach the liquid formulation of etelcalcetide transferred to unit dosage or multiple-dosage containers of bottles or vials (p16, line 15-16) or glass vials at pH 3.5 (p23, Example 4, line 14-15).
Maclean et al. do not teach add surfactant to the liquid protein formulation (e.g., etelcalcetide) to reduce absorption of the therapeutic protein to a contacted surface such as a filter of sterile filtration or inside surface of a storage vial.
Mahler et al. teach commonly used stabilizers in marketed products as well as those in development are surfactants like polysorbate 20 (Tween1 20) and polysorbate 80 (Tween1 80) known in the art (p2620, col 1, Introduction, para 1). Mahler et al. suggest surfactants (e.g., polysorbate 20 and polysorbate 80) often included in a protein formulation for protection of the protein against mechanical stress or freezing/thawing stress, which are otherwise known to induce protein aggregation in the absence of sufficient concentration of a stabilizer (p2620, col 1, Introduction, para 2). Mahler et al. teach protein is exposed to a number of surfaces during manufacturing (e.g., tubings, filters), storage (e.g., glass and rubber stoppers), and administration (e.g., infusion tubings and bags). To prevent adsorption of the protein to surfaces, surfactants are commonly used (p2620, col 1, Introduction, para 2 bridging to col 2, para 1). Because Mahler et al. teach polysorbate 20 (Tween1 20) and polysorbate 80 (Tween1 80) are commonly used as stabilizer for protein/peptide formulation and these surfactants are able to beneficially prevent adsorption of the protein to surfaces (e.g., tubings, filters, glass vials, rubber stopper and infusion bags), one of ordinary skill in the art would have found it obvious to beneficial add a surfactant (e.g., polysorbate 20 or polysorbate 80) in formulation of Maclean’s liquid formulation of etelcalcetide stored in a glass vial, reading on the limitation (ii) of surfactant.
One of ordinary skill in the art before the effective filing date of this invention would have found it obvious to combine (i) Maclean’s liquid formulation of etelcalcetide stored in a glass vial with (ii) Mahler’s stabilizers of polysorbate 20 and polysorbate 80 because Mahler et al. suggest (a) surfactants (e.g., polysorbate 20 and polysorbate 80) often included in a protein formulation for protection of the protein against mechanical stress and (b) the use of surfactant of polysorbate 20 or polysorbate 80 to prevent adsorption of the protein to contacted surfaces such as glass vials of storage (p2620, col 1, Introduction, para 2 bridging to col 2, para 1). The combination would have reasonable expectation of success because both references teach peptide formulation for storage in glass vials.
With respect to claim 2, Maclean et al. teach the pH of etelcalcetide formulation has a pH of 3.0 to 3.5 to 3.0 to 4.0 (p2, line 20-21).
With respect to claim 4, Maclean et al. teach the use of succinate buffers, acetate buffers, citrate buffers or phosphate buffers to achieve a desired pH (p2, 23-27).
With respect to claim 6, Mahler et al. teach polysorbate 20 (Tween1 20) and polysorbate 80 (Tween1 80) are commonly used as stabilizer for protein/peptide formulation and these surfactants are able to beneficially prevent adsorption of the protein to surfaces (e.g., tubings, filters, glass vials, rubber stopper and infusion bags).
With respect to claim 8, Mahler et al. suggest the use polysorbate surfactant at 0.01% (w/v) to reduce protein absorption to a contact surface (p2623, col 2, last 2 para) shown in Table 3 (p2624).
With respect to claim 9, Mahler et al. teach the amount of etelcalcetide is from 2 mg/ml to 20 mg/ml (p15, in a succinate buffer at pH 3.0 to 3.5 and a sufficient concentration of sodium chloride (p15, 27-30).
With respect to claims 11-12, Mahler et al. teach the choice of tonicity modifier as NaCl or mannitol), (p28, line 18).
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 1-2, 4, 6, 8-9, and 11-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 9, and 11 of U.S. Patent No. 11,162,500 B2 (the ‘500 patent) in view of Maclean et al. (WO 2014/210489 A1, cited in IDS) in view of Mahler et al. (J Pharm Sci. 2010 Jun;99(6):2620-7.10).
Claim 1 of the ‘500 patent disclosed a pharmaceutical formulation of etelcalcetide as follows.
PNG
media_image1.png
74
404
media_image1.png
Greyscale
Claims 4-5 of the ‘500 patent disclosed the pH is maintained by succinate buffer.
Claims 9 and 11 of the ‘500 patent disclosed the pharmaceutical formulation further comprising a pharmaceutically acceptable tonicity modifier of sodium chloride.
Claims 1, 4-5, 9, and 11 of the ‘500 patent did not specify the formulation further beneficially comprising surfactant.
The relevancy of Maclean et al. in view of Mahler et al. teach claims 1-2, 4, 6, 8-9, and 11-12 described above not repeated here.
Because Mahler et al. teach polysorbate 20 (Tween1 20) and polysorbate 80 (Tween1 80) are commonly used as stabilizer for protein/peptide formulation and these surfactants are able to beneficially prevent adsorption of the protein to surfaces (e.g., tubings, filters, glass vials, rubber stopper and infusion bags), one of ordinary skill in the art would have found it obvious to add Mahler’s surfactant (polysorbate 20 and/or polysorbate 80) to the etelcalcetide formulation taught by claims 1, 4-5, 9, and 11 of the ‘500 patent.
Thus, claims 1, 4-5, 9, and 11 of the ‘500 patent in view of Maclean et al. and Mahler et al. are obvious to the instant claims 1-2, 4, 6, 8-9, and 11-12.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIA-HAI LEE whose telephone number is (571)270-1691. The examiner can normally be reached Mon-Fri from 9:00 AM to 6:00 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, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.L/Examiner, Art Unit 1658
05-September-2026
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
Prosecution Insights