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 .
Claim Status
Claims 3-4, 6-10, 13-14, 16-17, 20, 28-29, 31, 33-35, 37, 39, 41, 43-44, 47-49, 51-53, 56, 59-61, 63, 65, 67, 69, 71-73, 75-76, 78, 83-84, 86-90, 92-94, 96-97, 99, 102, 104, and 106-125 are cancelled. Claims 1-2, 5, 11-12, 15, 18-19, 21-27, 30, 36, 38, 40, 42, 45-46, 50, 54-55, 57-58, 62, 64, 66, 68, 70, 74, 77, 79-82, 85, 91, 95, 98, 100-101, 103, and 105 as filed on 25 September 2025 are pending. Claims 12, 15, 19, 21-26, and 54 are withdrawn. Claims 1-2, 5, 11, 18, 27, 30, 32, 36, 38, 40, 42, 45-46, 50, 55, 57-58, 62, 64, 66, 68, 70, 74, 77, 79-82, 85, 91, 95, 98, 100-101, 103, and 105 are under examination.
Claims 32 and 42 are rejoined and not withdrawn as previously noted.
Both claims were rejected under the art and the rejection remains below.
Rejections Withdrawn
Rejection of claims 1-2, 27, 80-81, 91, 100-101, 103, and 105 under 35 U.S.C. 102(a)(1) is withdrawn with applicant amendment of claims.
Rejection of claims 11-2, 27, 32, 36, 38, 40, 45-46, 55, 57-58, 62, 66, 68, 70, 74, 77, 79-82, 85, 91, 95, 98, 100-101, 103, and 105 under anticipatory double patenting for copending Application No. 18002613 with applicant amendment of claims.
Rejection of claims under double patenting for copending Application No. 18578137 with abandonment of copending application.
Rejection of claims under double patenting for copending Application No. 18685666 with abandonment of copending application.
Rejection of claims under double patenting for copending Application No. 18726350 with abandonment of copending application.
Applicant arguments related to withdrawn rejections have not been responded to.
Rejections Maintained – Amended as Necessitated by Applicant Amendment of 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.
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.
Claims 1-2, 5, 11, 18, 27, 30, 45-46, 50, 79-82, 91, 100-101, 103, and 105 are rejected under 35 U.S.C. 103 as being unpatentable over Aukerman (WO 2005086798 A2) (IDS 03/15/2022 FOR 1) and Butz (WO 2016/164937 A2) (IDS 12/20/2022 FOR 1).
Instant SEQ ID NO: 1 matches Aukerman SEQ ID NO: 2 and instant SEQ ID NO: 1 and Aukerman SEQ ID NO: 2 comprise instant SEQ ID NO: 84.
Regarding claims 1-2 and 27, Aukerman teaches the amino acid of SEQ ID NO: 2 (claim 5 in subpart b). Aukerman teaches the modification of IL-2 in substitutions of amino acids at positions H16, P65, and D84 (claim 8).
Regarding claims 5, 11, and 18, Aukerman teaches the combination of amino acid substitutions of H16D or H16E, P65R and D84R (claim 8).
Regarding claims 80, Aukerman by teaching the substitutions encompassed by claim 1 would have the biological activity of claim 80.
Regarding claim 81, Aukerman teaches the mutated IL-2 is fused to a second protein (page 54 in lines 15-19).
Regarding claim 91, claim 91 is read to include a first polypeptide fused to a second polypeptide wherein the first polypeptide is the modified IL-2 and the second polypeptide is not a modified IL-2. Aukerman teaches the mutated IL-2 is fused to a second protein (page 54 in lines 15-19). Aukerman further teaches the second polypeptide is a human albumin (page 54 in lines 20-21).
Regarding claim 100, Aukerman teaches a pharmaceutical composition comprising a modified IL-2 in a pharmaceutical composition with a pharmaceutically acceptable carrier (Abstract and claim 29).
Regarding claims 101 and 103, Aukerman teaches a nucleic acid encoding modified IL-2 in a host cell comprising the nucleic acid (claims 1-4).
Regarding claim 105, Aukerman teaches the method of producing the polypeptides of modified IL-2 wherein the a host cell is incubated under conditions that produce the modified IL-2 (claim 27).
Aukerman teaches a decrease in pro-inflammatory responses with the IL-2 mutations of their invention for use in human treatment (page 8 in lines 28-31, page 12 in lines 5-15, and claim 30).
Aukerman does not teach the combination of amino acid substitutions required by claims 5, 11, and 18 or elected by applicant of H16A and D84S. Aukerman does not teach a fusion to an IgG1 Fc.
These deficiencies are filled by Butz.
Butz teaches mutated IL-2 alone and in a fusion molecule with an Fc (abstract).
Butz teaches the fusion of IL-2 fused to an IgG1-Fc domain improves half-life which reduces dosing frequency (Example 2 in pages 55-57).
Regarding claims 5, 11, and 18, Butz teaches multiple IL-2 mutations including H16A and D84S in the same mutation along with further substitutions (page 2 in par 3 and claim 1).
Regarding claims 30, 45-46, 50, and 82, Butz teaches the mutated IL-2 is fused to an Fc protein (claims 6-7). Butz teaches fusion to the C-terminus of the Fc with a linker comprising GGGGS (page 56 in par 2) Butz teaches fusion comprising IgG1 Fc (abstract and sequences on page 59-60). Instant SEQ ID NO: 47 is the wild type sequence for IgG1 meaning the IgG1 of Butz would teach this sequence thus teachings claim 45.
Regarding claim 79, Butz teaches the IL-2 mutation fused to Fc forms a homodimer (Figure 6, page 56 last paragraph and page 57 in par 1).
Butz teaches the use of their IL-2 mutein fused to Fc as a method of increasing the ration of T regs to non-regulatory T cells in a human patient (claims 59, 62, and 69). Butz teaches a method comprising administering the fusion protein in the treatment of inflammatory or autoimmune diseases (claim 71).
It would have been obvious to one of ordinary skill in the art to combine the amino acid substitutions of Aukerman with the amino acid substitutions of Butz and to further substitute the second polypeptide in the fusions of Aukerman with the Fc of Butz. Aukerman and Butz both teach the use of mutated IL-2 in fusions for use in human subjects both decreasing inflammation in the subject making the combination of amino acid substitutions P65R, H16A, and D84S obvious. This is the combination required by certain claims and elected by applicant. One of ordinary skill in the art would have been motivated to substitute the second polypeptide of the fusion of Aukerman with the IgG1 Fc of Butz as Butz fusion of IL-2 fused to an IgG1-Fc domain improves half-life which reduces dosing frequency. The decreased dosing improves patient adherence as it decreases barriers to care and decreased risk of complications from administration of the fusion protein. There would have been a reasonable expectation of success as Aukerman and Butz both teach the pharmaceutical administration of mutant IL-2 to a patient population.
Applicant Arguments
Applicant argues that Aukerman and Butz does not teach or suggest the requirements of the claim of a substitution of H16A, P65R, and D84. Applicant argues Aukerman teaches additional substitutions of amino acids at other locations in the sequence. Applicant argues Aukerman teaches numerous substitutions and combinations without teaching the specific combination of the claims.
Applicant argues that Aukerman teaches away from the specific substitutions of interest of the claims.
Applicant argues Butz does not remedy the deficiencies of Aukerman. Applicant argues Butz teaches a laundry list of potential substitutions.
Applicant argues neither Aukerman nor Butz teaches the combination of P65R, H16A, and D84 substitutions.
Applicant argues significances of the combination of P65R, H16A, and D84 pointing to Figures 2, 4, and 13-14 and Examples 13-14 showing a particularly effective combination of substitutions. Applicant argues this overcomes the obviousness of the combination.
Response to Arguments
Applicant's arguments filed 24 September 2025 have been fully considered but they are not persuasive.
Aukerman teaches the substitution of amino acids at positions H16, P65, and D84 in claim 8 (page 8 in lines 6-27 and claim 8). Additional substitutions falls within the scope of the claims as the claims recite a modified IL-2 that “comprises” the substitutions of P65R, H16A, and D84. The art does not teach a modified IL-2 without further modifications.
While Aukerman teaches many positions for substitutions it does repeatedly highlight the positions of P65, H16, and D84. This is further supported by the teachings of Butz to substitute amino acids at H16 and D84 (page 72 in par 2).
Butz teaches in Figure 15 that the boxed mutations (which includes H16A and multiple mutations of D84) altered the binding activity of IL-2 and were selected for further experimentation.
Aukerman and Butz teach the substitutions of the claims and teach their combination with additional substitutions which the claims allow for.
Figure 2 of the instant application shows a change in binding with the substitutions of P65R which Aukerman explicitly teaches and claims in its modified IL-2 (claim 8). Its presence with additional substitutions falls within the scope of the pending claims.
Figure 3 of the instant application additionally shows H16A and D84S have activity of interest.
Figures 13-14 shows changed binding and activity of IL-2-RAS which is a mutated IL-2 with the substitutions of P65R, H16A, and D84S ([00203] in Example 15).
The change in binding activity of IL-2-RAS does appear to be desirable and surprising in view of the art that teaches the substitutions but does not teach the full value of these substitutions of teach the exact combination of P65R, H16A, and D84S alone.
This argument does not overcome the rejection as the claims are to a modified IL-2 comprising P65R, H16A, and D84S and only claim 18 limits the substitution of D84S while other pending claims are to one that comprises P65R, H16A, and D84 and allows for additional substitutions.
Claims 1, 30, 32, 36, 42, 57-58, 62, 64, 66, 68, 70, 77, 85, and 88 are rejected under 35 U.S.C. 103 as being unpatentable over Aukerman (WO 2005086798 A2) (IDS 03/15/2022 FOR 1) and Butz (WO 2016/164937 A2) (IDS 12/20/2022 FOR 1) as applied to claims 1-2, 5, 11, 18, 27, 30, 45-46, 50, 79-82, 91, 100-101, 103, and 105 above, and further in view of Codarri (WO 2018/185043 A1) (Of Record Hereafter “Codarri ‘043”) and Codarri (WO 2018/184965 A1) (Of Record Hereafter “Codarri ‘965”).
The teachings from Aukerman and Butz from the previous art rejections are incorporated here in full.
Aukerman in view of Butz teaches a modified IL-2 for therapeutic applications that can be used in fusion proteins as explained in the previous rejections including fusions to Fc, and antibodies. Including teaching the Fc forming a homodimer.
As claims 1 and 30 are obvious over Aukermann and Butz they would be obvious over Aukermann and Butz in view of Codarri ‘043 and Codarri ‘965.
Butz further teaches the mutation of the Fc to alter the effector function with either increasing or decreasing its effector function (page 24 in par 2 and page 25 in par 2).
Aukerman in view of Butz does not teach the specific amino acid substitutions of the Fc of the claims, or the fusion of a modified IL-2 with antibodies that bind multiple targets, or the binding of PD-1.
These deficiencies are filled by Codarri ‘043 and Codarri ‘965.
Codarri ‘043 teaches an immunoconjugate comprising a bispecific antigen binding molecule that binds to PD-1 and Lag-3 (abstract and claim 1). Codarri ‘043 teaches the “knob-into-into” technology to form heterodimers in Fc regions (page 33 in lines 8-13). Codarri ‘043 further teaches the immunoconjugates can comprise linkers to further moieties including drugs (page 38 in lines 35-37). Codarri ‘043 teaches immunoconjugates include molecules such as cytotoxic agents (page 39 in lines 26-27). Codarri ‘043 further teaches immunoconjugates can comprise chemotherapeutic agents or drugs (page 84 in lines 2-5).
Regarding claims 32 and 36, Codarri ‘043 teaches the amino acid substitutions of T366W, Y449C, and S54C (page 33 in lines 17-24).
Regarding claims 42 and 85, Codarri ‘043 teaches the substitution of amino acids at positions E233, L234, and L235 (page 59 in lines 20-21) and further teaches L234A, L235A, and P329G as P329G LALA (Page 59 in line 28). Codarri ‘043 teaches P329G LALA completely abolishes Fcγ receptor binding of a human IgG1 Fc domain (page 59 in lines 28-29). Claim 85 requires only 1 of the listed modifications and the changes at E233, L234, and L235 fulfill the requirements of the claim.
Codarri ‘043 teaches the use of different dimerization recombinant products are advantageous to improve yield and purity of the bispecific antibodies making the known Fc substitutions of Codarri ‘043 a desired tool in production of bispecific molecules (page 62 in par 1).
Regarding claims 57-58, 62, and 77, mutant IL-2 polypeptide and bispecific antigen binding molecule that binds to PD-1 and TIM-3 (abstract and claim 1).
Regarding claims 64, 66, 68, and 70, Codarri ‘043 teaches single-domain antibodies include VHH (page 25 in lines 4-6 and page 21 in lines 25-30). Codarri ‘043 antigen-binding fragments that comprise a VH and a VL (Figure 1). Codarri ‘043 teaches the use of anti-PD1 antibodies that are humanized (page 8 in lines 1-4). Codarri ‘043 teaches single-chain Fab (claim 32).
Codarri ‘043 teaches the use of their bispecific antibodies comprising Fc mutations in the treatment of cancer (claims 48-50).
Codarri ‘965 teaches immunoconjugates comprising IL-2 with bispecific antibodies including mutant immunoconjugates (Title, abstract). Codarri ‘965 teaches the use of mutated IL-2 to modulate its effects to reduce its toxicity and/or increase its efficacy (page 4 in lines 1-2). Codarri ‘965 further teaches IL-2 immunotherapy may be improved by targeting IL-2 tumors with immunoconjugates that bind to antigens expressed on the tumors (page 4 in lines 24-28).
Codarri ‘965 teaches the use of mutated IL-2 in its immunoconjugates (claim 1).
Codarri ‘965 teaches the Fc of its bispecific immunoconjugates comprises mutations to the Fc including T366W (claim 18), S354C (claim 19), L234, L235, and P3229 (claims 25-26) including the P329G LALA taught by Codarri ‘043.
Codarri ‘965 teaches the use of this immunoconjugate in the treatment of multiple diseases including cancer (claims 37-39).
It would have been obvious to one of ordinary skill in the art at the time the application was filed to substitute the Fc and antigen binding domains linked to a mutant IL-2 taught by Aukerman in view of Butz with the modified Fc and antigen binding of PD-1 and Tim-3 or PD-1 and Lag-3 of Codarri ‘043 and Codarri ‘965 to produce an immunoconjugate comprising a mutant IL-2 of claim 1, 2 antigen-binding domains, and a modified Fc. Aukerman teaches IL-2 can be used in fusion proteins for the treatment of cancer. Aukerman, Butz, and Codarri ‘965 all teach the use of IL-2 in therapeutics with Aukerman teaching IL-2 can be used in the treatment of cancer and to reduce inflammation in human subjects. Codarri ’043, and Codarri ‘965 teach the use of immunoconjugates in the treatment of cancer and that their altered Fc domains provide advantages in yield and purity when producing multispecific immunotherapeutic. One of ordinary skill in the art would have been motivated to combine the known therapeutic of mutant IL-2 of Aukerman with the immunoconjugates taught by Codarri ’043, and Codarri ‘965 as those in the art knew IL-2 therapy may be improved by targeting IL-2 tumors with immunoconjugates that bind to antigens expressed on the tumors. The combination improves IL-2 delivery. The prior art of Aukerman, Butz, and Codarri ‘965 are to fusions comprising mutant IL-2 in the treatment of cancer making their combination obvious. The combination of Aukerman, Butz, and Codarri ‘965 with Codarri ’043 is obvious as Codarri ’043, and Codarri ‘965 are both teaching immunoconjugates for the treatment of cancer and Codarri ‘965 is teaching a bispecific immunoconjugate can use mutated IL-2 in the treatment of cancer. There would have been a reasonable expectation of success as IL-2 for use in immunoconjugates is well known in the art as shown by Codarri ‘965 and Butz.
Applicant Arguments
Applicant argues Codarri ‘043 and Codarri ‘965 do not cure the deficiencies of Aukerman and Butz previously argued.
Applicant argues the modified IL-2 of Codarri ‘965 has completely different function than the modified IL-2 of Aukerman and Butz.
Applicant argues an error in law that the rejection relies merely on its disclosure in the art making it known.
Response to Arguments
Applicant's arguments filed 24 September 2025 have been fully considered but they are not persuasive.
Regarding Aukerman and Butz examiner has responded to the arguments in the first art rejection.
As stated in the rejection of claim 30, Butz teaches the mutated IL-2 is fused to an Fc protein (claims 6-7). Butz teaches fusion to the C-terminus of the Fc with a linker comprising GGGGS (page 56 in par 2) Butz teaches fusion comprising IgG1 Fc (abstract and sequences on page 59-60).
Aukerman in view of Butz teaches a modified IL-2 for therapeutic applications that can be used in fusion proteins as explained in the previous rejections including fusions to Fc, and antibodies. Including teaching the Fc forming a homodimer. The rejection in view of Codarri ‘043 and Codarri ‘965 relies on the substitution of the Fc protein of Butz with the protein of Codarri ‘043 and Codarri ‘965. The activity of the IL-2 of Codarri ‘043 and Codarri ‘965 is not relied upon for the rejection.
Claims 1, 30, 38, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Aukerman (WO 2005086798 A2) (IDS 03/15/2022 FOR 1) and Butz (WO 2016/164937 A2) (IDS 12/20/2022 FOR 1) as applied to claims 1-2, 5, 11, 18, 27, 30, 45-46, 50, 79-82, 91, 100-101, 103, and 105 above, and further in view of Codarri (WO 2018/185043 A1) (Of Record Hereafter “Codarri ‘043”) and Codarri (WO 2018/184965 A1) (Of Record Hereafter “Codarri ‘965”), and Igawa (EP 2857420 A1) (Of Record).
The teachings from Aukerman and Butz from the previous art rejections are incorporated here in full.
Aukerman in view of Butz teaches a modified IL-2 for therapeutic applications that can be used in fusion proteins as explained in the previous rejections including fusions to Fc, and antibodies. Including teaching the Fc forming a homodimer.
As claims 1 and 30 are obvious over Aukermann and Butz they would be obvious over Aukermann and Butz in view of Codarri ‘043 and Codarri ‘965.
Butz further teaches the mutation of the Fc to alter the effector function with either increasing or decreasing its effector function (page 24 in par 2 and page 25 in par 2).
Aukermann does not teach the amino acid substitutions of M252Y and M428V in the Fc region.
These deficiencies are filled by Codarri ‘043, Codarri ‘965, and Igawa.
The teachings of Codarri ‘043 and Codarri ‘965 from the other art rejections are incorporated here in full.
Codarri ‘965 as previously stated teaches an immunoconjugate comprising a bispecific antigen binding molecule and a mutant IL-2 wherein the Fc has been altered to for dimerization.
Regarding claim 38 and 40, Igawa teaches multispecific molecules that dimerize for the purpose of therapeutic applications (abstract). Igawa teaches the substitutions M252Y and M428V in Table 2-7 in row F251 and teaches H435K or H435R in table 2-23 in rows F954 and F960.
It would have been obvious to one of ordinary skill in the art to substitute the dimerized Fc of the immunoconjugate taught by Aukermann in view of Butz, Codarri ‘043 and Codarri ‘965 with a dimerized Fc taught by Igawa. Codarri ‘965 and Igawa both teach T cell binding multispecific molecules with dimerized Fc created with amino acid substitutions making their substitution obvious. There would have been a reasonable expectation of success as T cell targeting multispecific molecules with dimerized Fc domains are analogous art and Codarri ‘043, Codarri ‘965, and Igawa like most art teaching the knob in hole methods teach the amino acid alterations in the Fc as art equivalents.
Applicant Arguments
Applicant argues Igawa does not cure the deficiencies of Aukerman and Butz previously argued.
Response to Arguments
Applicant's arguments filed 24 September 2025 have been fully considered but they are not persuasive.
Regarding Aukerman and Butz examiner has responded to the arguments in the first art rejection.
Claims 1, 81, 95, and 98 are rejected under 35 U.S.C. 103 as being unpatentable over Aukerman (WO 2005086798 A2) (IDS 03/15/2022 FOR 1), Butz (WO 2016/164937 A2) (IDS 12/20/2022 FOR 1), Codarri (WO 2018/185043 A1) (Of Record Hereafter “Codarri ‘043”), Codarri (WO 2018/184965 A1) (OF RECORD Hereafter “Codarri ‘965”), and Brinkmann and Kontermann. MABS 9(2):182-212. (2017) (OF RECORD).
The teachings of Aukerman from the 102 rejections are incorporated here in full.
As Aukerman anticipates claims 1 and 81 They would be obvious over Aukerman in view of Butz, Codarri ’043, Codarri ‘965, and Brinkmann.
Aukerman does not teach the configuration of the first and second polypeptides required by claim 95. Aukerman does not teach the first antigen-binding domain binding PD-1 and the second binding domain binding LAG3.
There deficiencies are filled by of Butz, Codarri ’043, Codarri ‘965, and Brinkmann.
The teachings of Butz, Codarri ’043, and Codarri ‘965 are incorporated here in full.
Codarri ‘965 teaches the first antigen binding domain fused to the N-terminus of the Fc region and the second polypeptide comprising the second-antigen binding domain and an Fc region (claim 22 and Figure 1). These are for a bispecific that binds PD-1 and Tim-3 (claim 1 and Figure 1).
Codarri ’043 teaches a bispecific domain comprising a first binding domain that binds PD-1 and is fused to the N-terminus of the Fc and a second antigen binding domain that binds LAG3 fused to an Fc region in Figure 1.
Brinkmann teaches zybodies which include peptides fused to the N or C terminus of heavy or light chains (Figure 2 and 196 col 2 in par 4). Brinkmann teaches multiple configurations of bispecific antibodies comprising IgG structures, multiple binding domains, including dimerization alterations to Fc domains for the use in therapeutics (abstract). Brinkmann teaches these configurations provide guidance for improved stability, solubility, and other parameters that confer drug properties (abstract).
It would have been obvious at the time the application was filed to substitute the general configuration of an immunoconjugate comprising mutant IL-2 and bispecific antibodies taught by Aukermann in view of Butz, Codarri ’043, and Codarri ‘965 and the specific configurations taught by Brinkmann. Aukermann in view of Butz, Codarri ’043, and Codarri ‘965 teach the use of IL-2 in fusion molecules for therapeutic applications. One of skill in the art would have been motivated to look at the known configurations of Brinkmann to produce a molecule that binds targets of interest in the treatment of cancer and have configurations known to be useful as therapeutics that maintain binding ability. There would have been a reasonable expectation of success as the configurations of Codarri ’043 and Codarri ‘965 are similar to those taught by Brinkmann and Brinkmann is providing a variety of known configurations for therapeutic applications.
Applicant Arguments
Applicant argues Brinkmann and Kontermann does not cure the deficiencies of Aukerman and Butz previously argued.
Response to Arguments
Applicant's arguments filed 24 September 2025 have been fully considered but they are not persuasive.
Regarding Aukerman and Butz examiner has responded to the arguments in the first art rejection.
Rejections Maintained – Amended as Necessitated by Applicant Amendment of Claims
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 1-2, 27, 32, 36, 38, 40, 45-46, 55, 57-58, 62, 66, 68, 70, 74, 77, 79-82, 85, 91, 95, 98, 100-101, 103, and 105 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 14-16, 30, 32, 43, 56-58, 65, 69, 76, 80-81, 84, 86-87, 89-90, 93, 95-96, 100, 108-110, 113, 117-118, 120, 129, 132, 142-144, 148, 153-154, 158, 163-164, 166, 168, 170, and 176-177 of copending Application No. 18002613 (reference application) in view of Aukerman (WO 2005086798 A2) (IDS 03/15/2022 FOR 1), Butz (WO 2016/164937 A2) (IDS 12/20/2022 FOR 1), and Codarri (WO 2018/185043 A1) (OF RECORD Hereafter “Codarri ‘043”)
Regarding claims 1-2, and 27, the reference application recites modified IL-2 comprising the substitutions of H16A, P65R, and D84 (claims 1, 3, 6, 43, and 69).
Regarding claim 30, the reference application recites the polypeptide comprises an Fc region wherein the IL-2 is fused to the C-terminus of the Fc region via a linker (claims 93 and 113).
Regarding claims 32, 36, 38,40, and 42, the reference application recites Fc substitutions including T366W, H435R, Y349C, M252Y, and a combination of L234A, L235A, and P329G (claims 96 and 110).
Regarding claims 45-46, reference application SEQ ID NO: 47 matches instant SEQ ID NO: 47. Instant SEQ ID NO: 47 is the wild type sequence for IgG1 meaning the IgG1 of the reference application would recite claim 45.
Regarding claims 55, 57-58, 62, 74, and 77, the reference application recites the polypeptide comprising one or more antigen binding domains including those that binds CD4+ or CD8+ T-cell, and PD-1 and LAG3 (claims 118 and 120).
Regarding claim 66, 68, and 70, the reference application recites binding domains of VHH, or VH and VL, or scFv (claim 129). The reference application recites the antigen binding domains bind PD-1 and LAG-3 (claim 120).
Regarding claim 80, the reference application recites the modified IL-2 binds to IL-2R with at least 2-fold lower affinity (claim 143).
Regarding claim 81, , the reference application recites first polypeptide and second polypeptide wherein the first polypeptide is the one of claim 1 (claim 144).
Regarding claim 81, Instant SEQ ID NO: 47 is the wild type sequence for IgG1 meaning the IgG1 of the reference application would recite claim 45. Instant SEQ ID NO: 87 matches SEQ ID NO: 87 of the reference application.
Regarding claim 85, the reference application recites Fc substitutions including T366W, H435R, Y349C, M252Y, and a combination of L234A, L235A, and P329G (claims 96 and 110).
Regarding claim 91, the reference application recites the second polypeptide does not comprise a modified IL-2 (claims 154 and 158).
Regarding claim 95, the reference application recites the first polypeptide comprises a first antigen binding domain, an Fc region and a modified IL-2 wherein the binding domain is fused to the N-terminus of the Fc and the IL-2 is fused to the C-terminus of the Fc and the second polypeptide comprising a second antigen binding domain fused to an Fc domain but does not comprise a modified IL-2 (claim 158)
Regarding claim 98, the reference application recites the antigen binding domains bind PD-1 and LAG-3 (claim 120).
Regarding claim 100, the reference application recites a pharmaceutical composition comprising a pharmaceutically acceptable carrier (claim 163).
Regarding claims 101 and 103, the reference application recites an isolated host cell comprising a nucleic acid encoding the polypeptide (claims 166 and 164).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The reference application does not recite the IL-2 amino acid substitution of D84S, the glycine or glycine and serine amino acids, or the human or humanized binding domain.
These deficiencies are filled by Aukermann, Butz, and Codarri ‘043.
The teachings of Aukermann, Butz, and Codarri ‘043 from the previous art rejections are incorporated here in full.
It would have been obvious to one of ordinary skill in the art to substitute the general recitations of the D84, linker, and antigen binding domains with the specifics of a D84S substitution taught by Aukermann, glycine-serine linker taught by Butz and the humanized binding domain taught by Codarri ‘043. The reference application already recites amino acid substitutions at D84 and Aukermann provides the amino acid substitution of D84S for use in combination with the substitutions recited by the reference application making the substitution obvious. The substitution of the general linker recited by the reference application with the linker taught by Butz that works with modified IL-2 in an immunoconjugate as taught by Butz, and to further substitute the general antigen binding domains of anti-PD-1 and anti-LAG3 with humanized PD-1 and humanized Lag-3 taught by Codarri ‘043 as both are PD-1 and LAG-3 binding domains in an immunoconjugate for treatment of humans. There would have been a reasonable expectation of success as the reference application, Aukermann, Butz, and Codarri ‘043 all teach treatment of human subjects.
This is a provisional nonstatutory double patenting rejection.
Applicant Arguments
Applicant requests the pending double patenting rejections be held in abeyance.
Response to Arguments
There are art rejections maintained and double patenting rejections maintained.
Examiner notes the 35 U.S.C. 120 date for the pending application is 01/06/2020 and for the reference application is 07/01/2021.
Conclusion
No Claims allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/F.E./Examiner, Art Unit 1643
/Meera Natarajan/Primary Examiner, Art Unit 1643
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