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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 September 4, 2025 has been entered.
Claim Status
Claim listing filed on September 4, 2025 is pending. Claims 2-6, 8, 10-16, 18-19, 21-27, 29-30, 32, 40, 42-44, 46, and 48-50 are canceled. Claims 1 and 9 are amended. Claims 1, 7, 9, 17, 20, 28, 31, 33-39, 41, 45, and 47 are examined upon their merits.
Withdrawn Claim Rejections
Any rejection of record pertaining to canceled claims 2, 10, 12, 21, and 23 have been rendered moot by Applicant’s amendment.
The rejection of claims 1, 7, 9, 17, 20, 28, 31, 33-39, 41, 45, and 47 under 35 U.S.C. 112(b) as being indefinite are withdrawn in view of Applicant’s amendments to Claim 1. In particular, “wherein said single-chain immunocytokine binds to a polypeptide complex comprising an interleukin-2 receptor-α(IL-2Rα) polypeptide, an interleukin-2 receptor-β(IL-2Rβ) polypeptide, and a common gamma chain (γc) polypeptide (an IL-2Rα/IL-2Rβ/γc polypeptide complex), thereby specifically stimulating regulatory T cells (Tregs) and not stimulating effector T cells” is clear and interpreted as an inherent functional property of the single-chain immunocytokine comprising SEQ ID NOs: 4, 9, and 10 (MPEP § 2112.01).
The rejection of claims 1, 7, 9, 17, 20, 28, 31, 33-39, 41, 45, and 47 under 35 U.S.C. 112(a) as failing to comply with the written description and enablement requirements is withdrawn in view of Applicant’s amendments to Claim 1. Claim 1 is no longer directed to a genus of possible immunocytokines and is instead directed to a species of immunocytokine comprising SEQ ID NOs: 4, 9, and 10.
The rejection of claims 1, 7, 9, 17, 20, 28, 31, 33-38, 41, and 47 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 12,151,000 in view of Tomala et al. ACS Chem Biol. 2013 is withdrawn due to the terminal disclaimer filed on September 4, 2025.
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
Claims 7 and 17 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.
Claim 7 is indefinite because it depends from cancelled Claim 2. Claim 17 is indefinite because it depends from cancelled Claim 12. For the purpose of compact prosecution, Claim 7 is interpreted as depending from Claim 1, and Claim 17 is interpreted as depending from Claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 103 (Maintained)
The rejection of Claims 1, 7, 9, 17, 20, 28, 31, 33-39, 41, 45, and 47 under 35 U.S.C. 103 as being unpatentable over Campbell WO 2017/220989 (of record) as evidenced by Collins Eur J Immunol 1989 (of record), and further in view of Rondon WO 2017/070561 (of record) and Tomala et al. ACS Chem Biol. 2013 (of record) is maintained.
Applicant's arguments filed September 4, 2025 have been fully considered but they are not persuasive. Applicant argues that the cited documents, alone or in combination, fail to teach or even suggest a single-chain immunocytokine that binds to an IL-2Rα/IL-2Rβ/γc polypeptide complex, thereby specifically stimulating Tregs and not stimulating effector T cells. Claim 1 is directed to a single-chain immunocytokine comprising an immunoglobulin heavy chain variable domain comprising SEQ ID NO: 4, an IL-2 polypeptide comprising SEQ ID NO: 9, and an immunoglobulin light chain variable domain comprising SEQ ID NO: 10 wherein the single-chain immunocytokine binds to a IL-2Rα/IL-2Rβ/γc polypeptide complex thereby specifically stimulating Tregs and not stimulating effector T cells. Claim 1 is interpreted wherein the binding properties and Treg stimulating functions are inherent properties of the immunocytokine structure comprising SEQ ID NOs: 4, 9, and 10 (MPEP § 2112.01 and of record in the final rejection filed 06/11/2025 [page 6]). Therefore, the prior art of record that teaches a single-chain immunocytokine comprising SEQ ID NOs: 4, 9, and 10 also makes obvious the inherent functional properties of the recited structure. Specifically, Rondon teaches an anti-IL-2 antibody complexed with human IL-2 wherein the anti-IL-2 antibody comprises heavy and light chain variable domains comprising SEQ ID NOs: 5 and 6 respectively which are 100% identical to instant SEQ ID NOs: 4 and 10 (of record). Campbell teaches single-chain immunocytokines comprising IL-2 (of record), and Tomala teaches that the motivation to design the IL-2/anti-IL-2 complex of Rondon into a single-chain immunocytokine as taught by Campbell is because the immunocytokine design eliminates disadvantages of immunocomplexes like excess IL-2 or anti-IL-2 antibody when the complex disassociates (of record).
Applicant argues that the inventors designed a single-chain immunocytokine having surprising and unexpected binding properties (i.e., the ability to bind to an IL-2Rα/IL-2Rβ/γc polypeptide complex) and function (i.e., the ability to specifically stimulate Tregs but not stimulate effector T cells). These functions are not surprising in view of Rondon. Rondon teaches that the IL-2/anti-IL-2 complex enhances Treg cell proliferation (of record). More specifically, Rondon teaches that the anti-IL-2 antibody blocks hIL-2 binding to IL-2Rβ and reduces but does not abrogate hIL-2 binding to IL-2Rα (paragraph [0076] and Figures 1-2). The resulting anti-IL-2 antibody function inhibits proliferation of non-Treg cells more than it inhibits proliferation of Treg cells; increases Treg proliferation as compared to a control antibody; and/or increases the ratio of Treg cells to non-Treg cells (paragraph [0076]). The stimulation of Treg proliferation is therapeutic in autoimmune diseases and graft-versus-host disease (paragraph [0077]). Therefore, it is not surprising and unexpected that the immunocytokine of the instant application specifically stimulates Tregs and not effector T cells, because Rondon teaches that the IL-2/anti-IL-2 complex comprising the same heavy and light chain variable domains has the same function. Note, the new sections of Rondon are cited solely in response to Applicant’s arguments and not as a new ground of rejection.
Applicant argues that neither Campbell nor Collins suggests the binding properties and Treg specificity of the instantly claimed immunocytokine. However, these arguments are addressed by the teachings of Rondon in the paragraph above.
Applicant argues that the IL-2/anti-IL-2 complex of Rondon is designed to “reduce the affinity of IL-2 binding to IL-2Rα and Il-2β” and one of ordinary skill would not be motivated to use the complex in an effort to design a molecule intended to bind an IL-2Rα/IL-2Rβ/γc polypeptide complex. It is outlined above how the complex of Rondon is understood to specifically stimulate Treg cells over other T cell types. The only difference between the complex of Rondon and the instant immunocytokine is that the instant immunocytokine is an anti-IL-2 scFv connected to IL-2 via a peptide linker (i.e. single-chain immunocytokine). The format of the single-chain immunocytokine was known in the art prior to filing (Campbell) as was the benefit of immunocytokines over immunocomplexes (Tomala). Thus, the Examiner is not relying on the motivation to design a molecule intended to bind an IL-2Rα/IL-2Rβ/γc polypeptide complex as recited by Applicant. MPEP § 2144.IV teaches that Examiner can rely on a different rational/motivation to establish a prima facie case of obviousness than is used by the Applicant. The fact that the Applicant may have a different intended purpose does not alter the conclusion that the molecule is prima facie obvious from the disclosed references.
Applicant argues that a person of ordinary skill would not reasonably expect the combined references to result in a single-chain immunocytokine that could successfully bind IL-2α/IL-2Rβ/γc polypeptide complex, and it is only with impermissible hindsight that the Office could have arrived at the presently claimed single-chain immunocytokine. It is of record how one of ordinary skill would arrive at the presently claimed single-chain immunocytokine with a reasonable expectation of success, and the Examiner relies solely on the prior art of record and not on the instant specification with impermissible hindsight reasoning. Further, Examiner notes that the discovery of a previously unappreciated property of a prior art composition (such as a binding property) or a scientific explanation of the prior art’s functioning (such as a mechanism of action), does not render the old composition patentably new to the discoverer (MPEP § 2112.I).
Conclusion
No claim is allowed.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675