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 .
1. Formal Matters
Claims 1, 18, 47, 50, 52, 53, 56, 57, 59, 61, 63, 64, 66, 69, 71, 74, 76, 79, 209 and 210 are pending and are the subject of this Office Action.
2. Claim Objections
Claim 1 is objected to since it should recite “and” before (ii).
3. Information Disclosure Statement
The IDS filed 8/30/24 is duplicate of that filed 7/22/24.
4. Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
A. Claims 1, 18, 47, 50, 52, 209 and 210 are rejected under 35 U.S.C. 103 as being unpatentable over Doshi et al. in view of Faghihi et al.
Doshi teaches the use of denosumab, which comprises SEQ ID NO:1 and 2 of claim 1, as disclosed in the instant Sequence Listing. Bio-Rad teaches that denosumab is a fully human monoclonal antibody (IgG2/kappa). Bio-Rad is not being used as part of the rejection, but to show that the antibody contains a kappa LCCR and IgG2 HCCR.
Doshi does not teach the use of phenylalanine. However, Faghihi teaches that phenylalanine was the best inhibitor of antibody aggregation (Figure 1; paragraph 2 of the Discussion). It is noted that the instant claims are drawn to an aqueous composition, whereas the antibody-phenylalanine complex is spray dried. However, section 3.10 teaches reconstitution in water, which would meet the limitation of claim 1.
Given the fact that Faghihi showed that phenylalanine was a highly effective aggregation inhibitor, it would have been obvious to have used this amino acid in the formulation of Doshi.
Neither Doshi nor Faghihi teach the antibody concentrations of claims 1 (greater than 70 mg/ml) and 18 (about 120 mg/ml). However, claims 209 and 210 recite that the syringe comprises up to 1 ml of the formulation. Given this, it would be expected that the dose to be administered would be up to 120 mg (claim 18). Doshi teaches a dose of 30 – 180 mg (Abstract). In addition, and as also pertains to phenylalanine concentration (claims 47, 50, 52 and 53), where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”).
Regarding claims 209 and 210, though neither reference teaches pre-filled syringe, it would have been obvious to have used one with any desirable volume of formulation based on the volume required for injection since Amgen teaches that denosumab is for subcutaneous administration (section 2.1).
B. Claims 56, 57, 59, 61, 63, 64, 66, 69, 71, 74 and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Doshi et al. in view of Faghihi et al. further in view of Uchiyama (cited on the IDS filed 1/14/25).
The teachings of Doshi and Faghihi are seen in the above rejection. Neither teaches sorbitol, polysorbate 20, acetate, a pH of 5.0 – 5.1. However, Uchiyama teaches a formulation comprising denosumab, an acetate buffer at a pH of 5.0 – 5.5, the tonicity modifier sorbitol and 0.1% polysorbate 20 (Table 1, page 2044, last entry)
Regarding claims 59 and 69, see In re Aller above.
C. Claim 79 are rejected under 35 U.S.C. 103 as being unpatentable over Doshi et al. in view of Faghihi et al. further in view of Dias et al. (Abstract. Already on 892). The teaching of Doshi and Faghihi are seen in paragraph A of this rejection. Neither teaches a viscosity of 2 – 10 cP. However, Dias teaches that a concentration of 5 cP is characteristic of high-concentration antibody formulas (Abstract), which the instant claims recite.
5. Nonstatutory 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.
A. Claims 1, 18, 47, 50, 52, 53, 56, 57, 59, 61, 63, 64, 66, 69, 71, 74, 76, 79, 209 and 210 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7, 8, 10, 13, 19, 25, 26, 28, 29 and 31-37 of U.S. Patent No. 11,192,592 (16/608,375). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to essentially the same formulation.
It is noted that the instant application is not a DIV of ‘592 and, therefore, does not receive safe-harbor protection. See Pfizer Inc. v. Teva Pharmaceuticals USA Inc., 86 USPQ2d 1001 (Fed. Cir. 2008).
The anti-RANKL antibody recited in instant claim 1 encompasses denosumab, which comprises instant the light chain (SEQ ID NO:1 plus human kappa LCCR) of SEQ ID NO:13 and the heavy chain (SEQ ID NO:2 and IgG2 HCCR) of SEQ ID NO:14. This is the same antibody recited in patent claim 35, which encompasses claims 33 and 34. Also see claims 31 and 32.
Patent claims 33-36 depend from claim 1, which recite an aggregation inhibitor, including phenylalanine (patent claim 2). These claims, in light of claim 19, meet the concentration of instant claim 1, whereas patent claim 23 meets instant claim 18. Instant claims 47 and 50 are met by patent claims 7 and 36. Patent claim 8 meets instant claims 52, 53, 56 and 57. Claim 59 is met by patent claim 29. Claims 28 and 29 meet instant claims 61, 63 and 64. Instant claims 66, 69 and 71 are met by patent claims 25 and 26. Patent claim 13 meets instant claims 74 and 76. Instant claim 79 is met by patent claim 10. Patent claim 37 meets instant claims 209 and 210 (it would have been obvious to have pre-filled the syringe with any desirable volume).
B. Claims 1, 18, 47, 50, 52, 53, 56, 57, 59, 61, 63, 64, 66, 69, 71, 74, 76, 79, 209 and 210 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-27 and 31-41 of U.S. Patent No. 11,873,343 (17/529,794). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to essentially the same formulations and containers comprising these formulations.
It is noted that the instant application is not a DIV of ‘343 and, therefore, does not receive safe-harbor protection. See Pfizer Inc. v. Teva Pharmaceuticals USA Inc., 86 USPQ2d 1001 (Fed. Cir. 2008).
Instant claims 1 and 18 are met by patent claims 38-41. Claims 47 and 50 are met by patent claim 41. Claims 52 and 53 are not specifically claimed in the patent. However, given that the patent claims recite the claimed antibody and phenylalanine concentrations, the molar ratio of the patent claims would be as instantly claimed. Claims 56, 57 and 59 are met by patent claims 31, 32 and 41. Instant claims 61, 63 and 64 are met by patent claims 35, 36 and 41. Claims 69 and 71 are met by patent claims 33 and 34. Instant claims 74 and 76 are met by patent claims 37 and 41.
Patent claim 1-8 and 10-27 recite the above limitations; however, the claims are drawn to a container comprising these formulations. Patent claims 1-4 meet instant claims 209 and 210 (it would have been obvious to have pre-filled the syringe with any desirable volume).
6. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647