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
The amendment filed June 9, 2026, is acknowledged and has been entered. Claims 2-11, 14, 17, 18, 20-22, 24, and 29 have been amended.
Claims 1-11, 14, 17-22, 24-25, 27, 29-34, 39 and 43 are pending in the application and are under examination.
Grounds of Rejection Withdrawn
Unless specifically reiterated below, Applicant's amendment has obviated or rendered moot the grounds of rejection set forth in the previous Office action.
Maintained Rejections
Claim Rejections - 35 USC § 102
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, 18, 20, 22, 25, 27, 30-34, 39 and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al (EP 3428193 B1, 2020).
With respect to claims 1, 22 and 25, Wang et al disclose an IL2 receptor (IL2R) binding protein that specifically binds to IL2Rβ and IL2Rγ, comprising an anti-IL2Rβ VHH antibody and an anti-IL2Rγ VHH antibody which can further comprise an Fc (see page 3, ¶10, (a bispecific antibody that binds IL2Rβ(CD122) and IL2Rγ (common gamma chain or CD132) and page 15, ¶111, wherein the bispecific antibody is a tandem VHH i.e., two VHHs linked by a linker and comprise a bispecific fusion protein with an Fc). With respect to claims 18 and 20, while Wang et al do not expressly teach an order of the two VHHs linked by a linker, one would at once envisage that the genus of tandem VHHs bispecific antibodies include one where the IL2Rβ antibody is at the N-terminus and another where the IL2Rγ antibody is at the N-terminus, so here the genus of Wang et al anticipates these two species (see MPEP § 2131.02).
With respect to claim 27, Wang et al disclose that the antibody can be conjugated to a drug including a PEG conjugate (i.e., the antibody is PEGylated) (see page 9, ¶ 60, page 10, ¶ 81 and page 26, ¶ 238). With respect to claims 30-32, Wang et al disclose nucleic acids in vectors encoding the antibody and such vectors in cells (see page 9). With respect to claim 33, Wang et al disclose the antibody in a pharmaceutical composition comprising a carrier (see page 23). With respect to claims 34, 39 and 43, Wang et al disclose treating cancer and viral infections and stimulating proliferation of T cells over other cells by administering the bispecific antibody (see pages 22 and 25).
Therefore, Wang et al is deemed to anticipate the instant claims absent a showing otherwise.
Applicant traverses the rejection, submitting that “The Examiner cited paragraph [0111] of Wang and asserted that Wang discloses bispecific IL2 receptor binding proteins comprising anti-IL2R3 and anti-IL2Ry VHH antibodies, including tandem VHH formats.
Applicant respectfully disagrees with this assessment. Paragraph [0111] begins with "Bispecific antibodies and fragments according to the invention may be provided in any suitable format, such as those formats described in Kontermann MAbs 2012, 4(2): 182-197, which is hereby incorporated by reference in its entirety." The paragraph includes a long list of antibody configurations, including "tandem dAb/VHH." It appears from the Office Action that the examiner is of the opinion that this term, "tandem dAb/VHH," relates to the claimed subject matter. The term itself is not used elsewhere in Wang and is undefined aside from the reference to the Kontermann reference (attached). The only place where "tandem dAb/VHH" is mentioned or described in Kontermann is Figure 2, which includes a cartoon picture of a wide variety of antibody configurations and the term "tandem dAb/VHH," without further textual explanation. It is not clear what exactly the term means given there is so little explanation in Kontermann, but it appears from the context and the term itself that it may refer a dAb in tandem with a VHH. As noted above, the present claims relate to an IL2R binding protein comprising a IL2R3 VHH sdAb and an anti-IL2Ry VHH sdAb and thus is different from a dAb in tandem with a VHH.”
In response, it is unclear what context Applicant is referring to suggest that the term "tandem dAb/VHH “may refer a dAb in tandem with a VHH”. Paragraph 111 states (emphasis added):
[0111] Bispecific antibodies and fragments according to the invention may be provided in any suitable format, such as those formats described in Kontermann MAbs 2012, 4(2): 182-197, which is hereby incorporated by reference in its entirety. For example, a bispecific antibody or bispecific antigen binding fragment may be a bispecific antibody conjugate (e.g. an IgG2, F(ab’)2 or CovX-Body), a bispecific IgG or IgG-like molecule (e.g. an IgG, scFv4-Ig, IgG-scFv, scFv-IgG, DVD-Ig, IgG-sVD, sVD-IgG, 2 in 1-IgG, mAb2, or Tandemab common LC), an asymmetric bispecific IgG or IgG-like molecule (e.g. a kih IgG, kih IgG common LC, CrossMab, kih IgG-scFab, mAb-Fv, charge pair or SEED-body), a small bispecific antibody molecule (e.g. a Diabody (Db), dsDb, DART, scDb, tandAbs, tandem scFv (taFv), tandem dAb/VHH, triple body, triple head, Fab-scFv, or F(ab’)2-scFv2), a bispecific Fc and CH3 fusion protein (e.g. a taFv-Fc, Di-diabody, scDb-CH3, scFv-Fc-scFv, HCAb-VHH, scFv-kih-Fc, or scFv-kih-CH3), or a bispecific fusion protein (e.g. a scFv2-albumin, scDb-albumin, taFv-toxin, DNL-Fab3, DNL-Fab4-IgG, DNL-Fab4-IgG-cytokine2).
It is apparent from this paragraph that bispecific fusions like a Fab-scFv are designated with a dash between each antigen binding domains, so the context does not support that a tandem dAb/VHH is limited to a dAb in tandem with a VHH. The context suggests that such a construct would have the designation dAb-VHH. These differences in paragraph 111 make it clear that the term tandem dAb/VHH encompasses a tandem dAb-dAb and a tandem VHH-VHH, while a tandem dAb-VHH would also be encompassed by the term. This position is clearly supported in the antibody art in general and Kontermann MAbs 2012 itself because in Figure 2 of Kontermann, the only construct with a backslash is tandem dAb/VHH. When constructs have different antigen-binding domains in Kontermann, like an Fab-scFv, a dash is used instead. As further evidence, before the effective filing date of the instant claims, Brinkmann and Kontermann (mAbs 9:2:182-212, 2017) further explain that a tandem dAb/VHH disclosed in Figure 2, box 3, include “two VHH domains … fused through a long hinge sequence derived from the upper hinge of the llama IgG2a” (see page 185, right column). Notably, this paragraph references Conrath (JBC, 10(9):7346-7350, 2001) which was published over 10 years before Kontermann MAbs 2012, 4(2): 182-197 and which discloses in figure 1 linking two VHH in tandem for constructing bispecific and bivalent antibodies. Similarly, Saerens et al (Current Opin. In Pharm. 8:600-608, 2008) discloses in 2008 that VHH can be used as building blocks of bispecific antibodies (see page 604 and Figure 2). Therefore, the plain reading of Wang et al supports that the bispecific tandem dAb/VHH disclosure from 2020 encompasses a VHH1-VHH2 construct comprising an anti-IL2Rβ VHH1 antibody and an anti-IL2Rγ VHH2 antibody and the evidence from Kontermann MAbs 2012, 4(2): 182-197 and other references also support this plain reading.
It is further noted that paragraph 111 discloses HCAb-VHH, and an HCAb is known in the art to comprise a VHH as instantly claimed linked to a CH2-CH3 domain, so an HCAb-VHH that binds IL2Rβ and IL2Rγ as disclosed by Wang et al, is also encompassed by the instant claims. Notably, the claims recite “open” language, i.e., “comprising an anti-IL2Rβ VHH antibody and an anti-IL2Rγ VHH antibody” such that the claims encompass a binding domain comprising other components like a CH2-CH3 domain of an HCAb.
Therefore, after further consideration this rejection is maintained.
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.
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(a) 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, 4-11, 14, 17-22, 24-25, 27, 29-34, 39 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (EP 3428193 B1, 2020), Kastelein et al (WO 2022/032006 A2, IDS) and Vivona et al (WO 2022/032884 A2, IDS)
Wang et al teach that which is set forth above. Wang et al do not disclose VHH antibody sequences encompassed by claims 4-11, 14, 17, 19, 21, 24 and 29.
Kastelein et al disclose the VHH sequences and CDR sequences of VHH antibodies that bind to IL2Rβ as set forth in instant claims 4-11, 14 and 29 (partial) in Table 1 at pages 5 and 6. Kastelein et al disclose that the antibody can be linked to another antibody in a bispecific antibody format at page 57.
Vivona et al disclose the VHH sequences and CDR sequences of VHH antibodies that bind to IL2Rγ as set forth in instant claims 4-11, 17 and 29 (partial) in Table 1 at pages 4-6. Vivona et al disclose that the antibody can be linked to another antibody in a bispecific antibody format at page 56.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to generate antibodies encompassed by claims 4-11, 14, 17, 19, 21, 24 and 29 by linking the VHH antibodies of Kastelein et al and Vivona et al in a tandem VHH antibody of Wang et al because the VHH antibodies of Kastelein et al and Vivona et al were art known and characterized VHH antibodies that could be predictably used in tandem VHH IL2Rβ and IL2Rγ bispecific antibodies. One would have been motivated to do so because generating such a tandem VHH could be made without difficulty, by routine steps, and with every expectation of success, such it would have been expected to bind both IL2Rβ and IL2Rγ. Making such tandem VHHs would be seen as combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results. Furthermore, the sequences of claims 19, 21 and 24 recite 90% identity language and as the prior art taught the VHH sequences, when the VHH antibodies of Kastelein et al and Vivona et al were constructed in the tandem VHH format the resulting proteins would be at least 90% identical to sequences in these claims because the sequences in these claims comprises the samer VHH sequences of Kastelein et al and Vivona et al.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references.
Applicant traverses the rejection, submitting that “Applicant submits that both Kastelein and Vivona were published on February 10, 2022, which is after the effective filing date of the instant application, January 11, 2021. Although Kastelein and Vivona can be cited as prior art references under 35 U.S.C. § 102(a)(2) based on their filing dates, they are disqualified as prior art under 35 U.S.C. § 102(b)(2)(C). This is because both Kastelein and Vivona are owned by Synthekine Inc., the owner of the instant application, they fall within this statutory exception under 35 USC § 102(b)(2)(C)” .
In response, it is unclear from this statement whether “the claimed invention of the application under examination and the subject matter disclosed in the U.S. patent document applied as prior art were owned by the same person or subject to an obligation of assignment to the same person not later than the effective filing date of the claimed invention” because the statement “both Kastelein and Vivona are owned by Synthekine Inc., the owner of the instant application” (emphasis added) which appears to reference current ownership. As set forth in MPEP § 2154.02(c) “A clear and conspicuous statement by the applicant (or the applicant's representative) that the claimed invention of the application under examination and the subject matter disclosed in the U.S. patent document applied as prior art were owned by the same person or subject to an obligation of assignment to the same person not later than the effective filing date of the claimed invention will be sufficient to establish that the 35 USC § 102(b)(2)(C) exception applies.
Accordingly, this rejection is maintained as a clear statement is not of record.
Conclusion
No claims are allowed. Claims 2-3 are objected to for depending upon a rejected base claim.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is 571-272-9935. The examiner can normally be reached Mon-Fri.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu, can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
August 26, 2026
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