DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1-4, 6-8, 10-13 and 15-24 are pending upon entry of amendment filed on 9/19/25.
3. Applicant’s submission of IDS filed on 9/19/25 has been considered.
4. In light of Applicant’s amendment to the claims filed on 9/19/25, the rejections under 35 U.S.C.112(a)(b) (see sections 6-10 of the office action mailed on 3/10/25) have been withdrawn.
5. The following rejections remain.
6. 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.
7. 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.
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.
8. Claims 1-4, 6-8, 10-13 and 15-24 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Pat. No. 6,538,111 (IDS reference, of record) in view of U.S. Pub. 2006/0088523 (IDS reference, of record) for the reasons set forth in the office action mailed on 3/20/25.
The ‘111 patent teaches antibodies comprising claimed SEQ ID NOs:5-10 (see claimed SEQ ID NOs:40-45, claim 8) and claimed SEQ ID No:1 (see claimed SEQ ID NO:71). The '111 patent teaches these antibodies specifically bind human IL-5R α chain that is expressed on human eosinophils which inhibit biological activities of human IL-5 (see col. 55, 79).
As specified in [0060] of the instant specification, the benralizumab is deemed IL-5R antibody set forth in SEQ ID NO:5-10 and reads on the antibody of the ’111 patent. It is deemed afucosylated in nature and claims 14 and 19 are included in this rejection.
The disclosure of the ‘111 patent differs from the instant claimed invention in that it does not teach the use of trehalose, histidine and polysorbate in antibody concentration of 30mg/ml as recited in claims 1-19 of the instant application.
The ‘523 publication teaches various exemplary formulations comprising antibody at 10-250mg/ml, histidine at 10-40mM of histidine buffer, about 0.01% polysorbate 20 and 60-250mM of trehalose as (claims 1-52). In addition, the ‘523 publication teaches the protein target includes interleukin receptors (p, 16, 21), articles of manufacture in various containers including syringes ([0399] readable upon prefilled as the containers are suitable for various administrations) needle, autoinjectors (p. 35) and the formulations comprising histidine, trehalose, polysorbate improves stability of antibody formulation (col. 8). Note the stability is determined to show no signs of aggregation upon storage at 40oC for at least one month (Tables) or formulation is stable at least 3 months at room temperature (p.33).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to add polysorbate, trehalose and/or histidine as taught by the ‘523 publication into the antibody taught by the '111 patent.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the addition of trehalose, polysorbate and histidine improve stability of antibody formulations by reducing aggregates and helps maintain osmolarity of formulation.
From the teachings of references, it would have been obvious to one of ordinary skill in art to combine the teachings of the references and there would have been a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of the ordinary in the art at the time of invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Applicant’s response filed on 9/19/25 has been fully considered but they were not persuasive.
Applicant has asserted that the combination is not obvious over the prior art, fails to address issues in claim 19 and dependent claims are not addressed (response p. 10-18). Further, there is no motivation or no expectation of success in combining the references as the ‘523 publication teaches no antibody set forth in CDR’s set forth in SEQ ID NO:5-10 binds IL-5R and Examiner is erred in applying the prior art of record.
Moreover, Applicant has asserted that the teachings of the ‘823 publication relates broader ranges such as 1ug/ml to about 500mg/ml of antibody and polysorbate of about 0.0005 to about 12% from the rejection of the related application of 16/298,474. Although claims are similar, Applicant is reminded that current rejection is not made with the 2005/0276823.
Unlike Applicant’s assertion, the issues of the dependent claims are collectively discussed. For example, the limitations of claim 19 storing at 40oC for 1 month is taught by the Tables 6-7 of the ‘523 publication. The tables 6-7 discloses SEC data showing monomer content greater than 99% after storage at 12months at 5oC and showing monomer content of 96.7% upon storage at 40oC for month, respectively. As such, the stability of the antibody comprising histidine, sucrose/trehalose and polysorbate is expected property. IN addition, the suggested polysorbate of 0.0001 to about 1% ([0376]) is taught and it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2145.
Applicant is reminded that the ‘111 patent provide the claimed antibody that binds IL-5R set forth in SEQ ID NO:5-10 (note SEQ ID Nos:40-45, for CDRs). In addition, the ‘111 patent teaches formulating IL-5R antibody in saline or other pharmaceutically acceptable carrier (col. 15).
However, the buffer, excipient as currently amended are suggested by the teachings of the ‘523 publication. Having the Applicant’s antibody formulations read on histidine, acetate, glycine or citrate, an excipient selected from trehalose, sucrose, sodium chloride and arginine at pH 5.5-6.5 in the presence of 0.002-0.007% polysorbate, the stable antibody formulation comprising a monoclonal antibody in histidine buffer at pH 5.5-6.5 in claim 1 of the ‘523 publication has a reasonable expectation of stabilizing IL-5R especially the stable antibody formulation comprising histidine buffer works for HER2, CD20, BR3, IgE or VEGF (note claims 1-25 of the ‘523 publication) in the presence of 0.0001-1% of polysorbate-20. In addition, throughout Examples 1-12 of the ‘523 publication, Apomab or pertuzumab was stable in histidine buffer. As Applicant claims benralizumab formulations read on histidine, acetate, glycine or citrate, an excipient selected from trehalose, sucrose, sodium chloride and arginine at pH 5.5-6.5 in the presence of 0.002-0.007% polysorbate, the stable antibody formulation comprising a monoclonal antibody in histidine buffer at pH 5.5-6.5 the stable antibody composition comprising buffer (e.g. histidine), excipient (e.g. trehalose) and polysorbate would have reasonable expectation of stabilizing IL-5R. Note the ‘523 publication teaches that the structurally different antibodies that bind each to HER2, CD20, DR5, BR3, IgE or VEGF were stabilized in histidine buffer comprising trehalose/sucrose and polysorbate (claims 1-25). They are all structurally different antibodies and recognize different antigen binding sites but formulated in histidine buffer.
As such, in lack of specific combination of buffer and excipient concentrations in stabilizing IL-5R antibody set forth in the SEQ ID NO:5-10, the combination of the references has provided reasonable expectation of success and predictability. Obviousness does not require absolute predictability, however, some degree of predictability is required. Evidence showing here was reasonable expectation of success may support a conclusion of nonobviousness. See MPEP 2143.02. The rejection is maintained.
9. 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.
10. Claims 1-4, 6-8, 10-13 and 15-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Application No. 16/298,474.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘474 application recites a stable aqueous antibody formulation comprising about 2-100mg/ml of antibody set forth in SEQ ID Nos:5-10 and 0.002-0.01% polysorbate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant has stated that the terminal claimer is submitted.
No terminal disclaimer is filed. The double patenting rejection is maintained.
11. No claims are allowable.
12. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YUNSOO KIM whose telephone number is (571)272-3176. The examiner can normally be reached on Mon-Fri 8:30-5. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Yunsoo Kim
Patent Examiner
Technology Center 1600
October 21, 2025
/YUNSOO KIM/Primary Examiner, Art Unit 1641