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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/22/2025 has been entered.
Applicant's arguments filed 8/22/2025 have been fully considered but they are not persuasive.
Claims 2-3, 5-8, 11-16, and 18 have been cancelled. Claims 30-31 have been newly added.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 1/22/2025 is again acknowledged.
Claims 17, 19-20, and 22-29 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/22/2025.
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 (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 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, 4, 9-10, 21, and 30-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (U.S. Patent Application Publication 2018/0362655, of record).
Wang et al. discloses anti-CD122 (i.e. anti-IL2Rb)/anti-IL2Rγ (also referenced as CD132) binding molecules that cause multimerization. Bispecific and bivalent antibodies are disclosed. See at least paragraphs [0006, 0012-0013, 0049, 0171]. The anti-CD122 and anti-IL2Rγ components of the binding molecules can be tandem dAb/VHH. See at least paragraphs [0185 and 0198]. They can be connected by linkers of 2-50 amino acids. See at least paragraph [0200]. Wang et al. does not require a particular order and so both orders are fairly encompassed as in instant claims 9-10. Pharmaceutical compositions are disclosed. See at least paragraphs [0165 and 0291].
Applicant’s argument that the term “tandem dAb/VHH” is unclear because it is not defined or explained in the Kontermann reference that is cited in Wang paragraph [0198] is unpersuasive. One of ordinary skill in the art would have understood that the phrase “tandem dAb/VHH” included tandem VHH. Figure 2, box 3, of Brinkmann et al. (2017) discloses tandem dAb/VHH where each of the antigen binding module symbols used in Figure 2, box 3, indicates dAb, Nb, VHH, or IgNAR as shown in Figure 1. See also section of bispecific single-domain antibody fusion proteins (page 185, right column). Brinkmann et al. provides a more detailed explanation of the structures disclosed in Kontermann et al. (2012, of record).
The disclosure of Wang et al. fairly discloses tandem VHH (i.e. VHH fused to VHH) as required by the 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, 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.
Claims 1, 4, 9-10, 21, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (U.S. Patent Application Publication 2018/0362655, of record) in view of Brinkmann et al., Ignatovich et al. (U.S. Patent Application Publication 2005/0271663), De Creus et al. (U.S. Patent Application Publication 2010/0303777).
Wang et al. is applied as above.
Figure 2, box 3, of Brinkmann et al. (2017) discloses tandem dAb/VHH where each of the antigen binding module symbols used in Figure 2, box 3, indicates dAb, Nb, VHH, or IgNAR as shown in Figure 1. See also section of bispecific single-domain antibody fusion proteins (page 185, right column). Brinkmann et al. provides a more detailed explanation of the structures disclosed in Kontermann et al. (2012, of record).
Ignatovich et al. (U.S. Patent Application Publication 2005/0271663) disclose that a VHH is defined as being a type of single domain antibody (also known as a dAb). This is acknowledged by the instant specification at least at paragraphs [0035 and 0093].
De Creus et al. (U.S. Patent Application Publication 2010/0303777) discloses making bivalent antibodies by fusing two single domain antibodies such as VHH with or without a linker. See at least paragraphs [0038-0042]. Paragraph [0018] discloses targets that include CD122 (i.e. IL2Rb in the instant claims) and CD132 (i.e. IL2Rγ in the instant claims).
It would have been obvious to make a bivalent antibody by fusing a first single domain antibody VHH against IL2Rb (also known as CD122) with a second single domain antibody VHH against IL2Rγ (also known as CD132) with or without a linker. Wang and De Creus et al. suggest such a bivalent antibody. This would have been a well known antibody structure as evidenced by Brinkmann et al. and Ignatovich et al. The first and second VHH could have been fused in either order. Wang et al. indicates that linkers of 2-50 amino acids would have been suitable. Wang et al. discloses formulating pharmaceutical compositions. One would have been motivated to produce the tandem VHH antibody as Wang et al. discloses that bispecific antibodies would have been useful and the format would have been conventional as evidenced by Brinkmann et al. and De Creus et al.
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, 4, 9-10, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 14, 17-22, 24-24, 27, and 33 of copending Application No. 18/260,709 (8/2/2024 claim set; same inventors and applicant as instant application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The co-pending application is a 371 application of PCT/US2022/012055 and is a CIP of PCT/US21/44853. It has a different priority claim than the instant application. Double patenting is not prohibited.
Co-pending claims 1-11, 14, 17-22, and 24-27 are directed to IL2 receptor (IL2R) binding proteins that specifically bind to IL2Rβ (i.e. IL2Rb in the instant claims) and IL2Rγ comprising an anti-IL2Rβ VHH antibody and an anti-IL2Rγ VHH antibody (see co-pending claim 1). These binding proteins meet the limitations of instant claims 1, 4, and 9-10. Note that sdAbs include VHH. (See instant claim 1 and at least paragraph [0092] of application 18/260,709.) The limitations of instant claims 9-10 are met by co-pending claims 18 and 20. The linker limitation of instant claim 1 is met by co-pending claims 22 and 24. The binding proteins of SEQ ID NOS: 65-289 in co-pending claim 24 meet the linker limitations of instant claims 1 and 4. See for example the linker GGGS at amino acids 123-126 of SEQ ID NO: 65. Co-pending claim 33 is directed to a pharmaceutical composition (see instant claim 21). The multimerizing activity recited in instant claim 1 would be inherent to the co-pending binding proteins as evidenced by the constructs of the instant specification.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4, 9-10, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 51-60 of copending Application No. 18/019,042 (2/14/2025 claim set; same applicant as instant application; common inventors Kastelein, Lupardus, and Rokkam). Although the claims at issue are not identical, they are not patentably distinct from each other.
The co-pending application is a 371 application of PCT/US2021/044730. It has a different priority claim than the instant application. Double patenting is not prohibited.
Co-pending claims 51-54 and 59-60 are directed to IL2 receptor (IL2R) binding proteins comprising an anti-CD122 (i.e. anti-IL2Rβ) VHH antibody and an anti-CD132 (i.e. IL2Rγ) VHH antibody (see co-pending claim 51) meeting the limitations of instant claim 1. See paragraph [0109] of the co-pending application with respect to the naming conventions. The binding protein linker limitations of instant claims 1 and 4 are met by co-pending claims 52-53. The multimerizing activity recited in instant claim 1 would be inherent to the co-pending binding proteins as evidenced by the constructs of the instant specification. See at least co-pending claim 54. The co-pending claims do not require any particular order and fairly include either order as recited in instant claims 9-10. Co-pending claims 55-58 are directed to methods of treatment by administering therapeutically effective amounts of the binding proteins. This clearly suggests formulation with a pharmaceutically acceptable carrier as in instant claim 21.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4, 9-10, 21, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,077,594 in view of Wang et al. and Brinkmann et al. (2017).
Claim 22 of the ‘594 patent is directed to an IL2Rg (i.e. IL2Rγ) binding molecule wherein the sdAb of claim 1 is linked to a second binding molecule that specifically binds to the extracellular domain of a second cell surface molecule. Note that Table 1 in the specification indicates that SEQ ID NOS: 1, 5, 9, 13, and so forth are IL2Rg (i.e. IL2Rγ) VHH sequences. See claim 2 of the ‘594 patent. Note that Table 3 in the specification indicates that SEQ ID NOS: 116, 120, 124, and so forth are IL2Rg (i.e. IL2Rγ) VHH sequences. See claim 4 of the ‘594 patent.
Wang et al. is applied as above.
Figure 2, box 3, of Brinkmann et al. (2017) discloses tandem dAb/VHH where each of the antigen binding module symbols used in Figure 2, box 3, indicates dAb, Nb, VHH, or IgNAR as shown in Figure 1. See also section of bispecific single-domain antibody fusion proteins (page 185, right column). Brinkmann et al. provides a more detailed explanation of the structures disclosed in Kontermann et al. (2012, of record).
It would have been obvious to use the IL2Rγ sdAb/VHH of the ‘594 claims in the bispecific IL2Rb/IL2Rγ tandem VHH constructs suggested by Wang et al. to arrive at binding molecules and pharmaceutical compositions of the instant claims. Wang et al. discloses linkers of 2-50 amino acids and pharmaceutical compositions. Issued claim 22 encompasses linking in either order.
Claims 1, 4, 9-10, 21, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 12,234,291 in view of Wang et al. and Brinkmann et al. (2017).
Claim 37 of the ‘291 patent is directed to an IL2Rb binding molecule wherein the sdAb of claim 1 is linked to a second binding molecule that specifically binds to the extracellular domain of a second cell surface molecule. Note that Table 1 in the specification indicates that SEQ ID NOS: 1, 5, 9, 13, and so forth are IL2Rb VHH sequences. See claim 2 of the ‘291 patent. Note that Table 3 in the specification indicates that SEQ ID NOS: 41, 45, 49, 53, and so forth are VHH sequences. See claim 4 of the ‘291 patent.
Wang et al. is applied as above.
Figure 2, box 3, of Brinkmann et al. (2017) discloses tandem dAb/VHH where each of the antigen binding module symbols used in Figure 2, box 3, indicates dAb, Nb, VHH, or IgNAR as shown in Figure 1. See also section of bispecific single-domain antibody fusion proteins (page 185, right column). Brinkmann et al. provides a more detailed explanation of the structures disclosed in Kontermann et al. (2012, of record).
It would have been obvious to use the IL2Rb sdAb/VHH of the ‘291 claims in the bispecific IL2Rb/IL2Rγ tandem VHH constructs suggested by Wang et al. to arrive at binding molecules and pharmaceutical compositions of the instant claims. Wang et al. discloses linkers of 2-50 amino acids and pharmaceutical compositions. Issued claim 37 encompasses linking in either order.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Buyse et al. (U.S. Patent Application Publication 2017/0121399) discloses bivalent and trivalent single domain antibodies (VHH) fused with peptide linkers. Suitable linkers include 9GS, 30GS or 35GS linkers. See at least paragraphs [0002, 0082-0085, 0349, 0362-0370, 0436, 0473, and 0793]; Figures 9B and 22-30; and legends under tables (such as Table AA) with respect to linkers.
Yu et al. (U.S. Patent Application Publication 2020/0071420) disclose tandem di-VHH antibodies. The VHH are connected by linkers. See at least Examples 1 and 2 (paragraphs [0082] and [0092]); SEQ ID NOS: 1 and 2; Figures 1 and 3; and page 4, embodiments #17 and #20.
Conclusion
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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