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
Status of the Claims
Claims 1 and 3-20 are the subject of this NON-FINAL Office Action. This is the first action on the merits.
Claim Rejections - 35 USC § 112- Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 and 3-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
In claim 1, “the internal ankyrin repeat” in line 2 lacks antecedent basis.
In claim 1, “the N-terminal capping module” in lines 2-3 lack antecedent basis.
Double Patenting- Obvious Type
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Instant claims 1 and 3-20 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-12 of U.S. 11242369, in view of US12331090 (effective filing 05/14/2020).
The instant claims are obvious over the conflicting claims because the conflicting claims clearly teach the same N-cap for ankyrin repeat proteins, and suggest to use familiar ankyrin repeats. Specifically, the conflicting claims teach the same N-cap, with any ankyrin repeat:
1. A method of preparing a protein comprising an ankyrin repeat domain with an improved thermostability, the method comprising the following steps (A) or (B):
(A) (i) providing a library with more than one protein, each protein comprising an ankyrin repeat domain that comprises an N-terminal capping module, one or more internal ankyrin repeat(s) and a C-terminal capping module,
and
(ii) selecting a protein having binding specificity to a target from the library of proteins of step (i), wherein the N-terminal capping module of the ankyrin repeat domain of said selected protein has an amino acid residue selected from the group consisting of I, T, A, V, L and M at the position corresponding to position 15 of SEQ ID NO: 58 and comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 58, and
wherein the thermostability of the ankyrin repeat domain of said selected protein is improved in comparison to a reference ankyrin repeat domain having the same amino acid sequence except for the amino acid residue at the position of the N-terminal capping module corresponding to position 15 of SEQ ID NO: 58, which is D in the reference ankyrin repeat domain;
or alternatively,
(B) (i) selecting a protein comprising an ankyrin repeat domain that comprises an N-terminal capping module, one or more internal ankyrin repeat(s) and a C-terminal capping module, and
(ii) replacing the N-terminal capping module of said ankyrin repeat domain by an N-terminal capping module that has an amino acid residue selected from the group consisting of I, T, A, V, L and M at the position corresponding to position 15 of SEQ ID NO: 58 and comprises an amino acid sequence that has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 58,
wherein the thermostability of said ankyrin repeat domain with the replaced N-terminal capping module is improved in comparison to a reference ankyrin repeat domain having the same amino acid sequence except for the amino acid residue at the position of the N-terminal capping module corresponding to position 15 of SEQ ID NO: 58, which is D in the reference ankyrin repeat domain.
2. The method according to claim 1, wherein the N-terminal capping module of the ankyrin repeat domain of said selected protein according to the method of claim 1 (A) or the N-terminal capping module of said ankyrin repeat domain with the replaced N-terminal capping module according to the method of claim 1 (B) comprises an amino acid sequence has at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 58.
3. The method according to claim 1, wherein the N-terminal capping module of the ankyrin repeat domain of said selected protein according to the method of claim 1 (A) or the N-terminal capping module of said ankyrin repeat domain with the replaced N-terminal capping module according to the method of claim 1 (B) comprises an amino acid sequence has at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 58.
4. The method according to claim 3, wherein the N-terminal capping module of the ankyrin repeat domain of said selected protein according to the method of claim 1 (A) or the N-terminal capping module of said ankyrin repeat domain with the replaced N-terminal capping module according to the method of claim 1 (B) has L at the position corresponding to position 15 and a dipeptide GS to N-terminal to the sequence having the at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 58; and
wherein said ankyrin repeat domain of said selected protein according to the method of claim 1 (A) or said ankyrin repeat domain with the replaced N-terminal capping module according to the method of claim 1 (B) comprises one or more internal ankyrin repeats that each have an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 81.
5. The method according to claim 1, the method comprising the step (A).
6. The method according to claim 1, the method comprising the step (B).
7. The method according to claim 1 (A), wherein the protein selected in step b) is further modified with one or more ankyrin repeat domains.
8. The method according to claim 7, wherein the modified protein comprises at least five ankyrin repeat domains.
9. The method according to claim 8, wherein, after modification with said ankyrin repeat domains, the protein is further formulated into a medicament.
10. The method according to claim 7, wherein the protein selected in step b) is further modified with one or more ankyrin repeat domains capable of binding to a mammalian serum albumin.
11. The method according to claim 10, wherein, after modification with one or more ankyrin repeat domains capable of binding to a mammalian serum albumin, the protein is further formulated into a medicament.
12. The method according to claim 4, wherein the ankyrin repeat domain of said selected protein according to the method of claim 1 (A) or said ankyrin repeat domain with the replaced N-terminal capping module according to the method of claim 1 (B) specifically binds to a virus.
One well-known ankyrin repeat directed to CD40 with “improved pharmacokinetic properties” and improved binding affinity for CD40 was SEQ ID NO: 3 of US12331090 (3.4. CD40 Binding Domains).
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As is clear from the comparison above, SEQ ID NO: 3 is identical to SEQ ID NO: 18, 35 or 91 with I at position 15. Thus, the conflicting claims, in light of well-known ankyrin CD40 binding domains, clearly suggest the instant claims.
Instant claims 1 and 3-20 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-13 and 16 of U.S. 18486851, in view of US12331090 (effective filing 05/14/2020).
The instant claims are obvious over the conflicting claims because the conflicting claims clearly teach the same N-cap for ankyrin repeat proteins, and suggest to use familiar ankyrin repeats. Specifically, the conflicting claims teach the same N-cap, with any ankyrin repeat:
1. A protein comprising an ankyrin repeat domain,
wherein the ankyrin repeat domain has an N-terminal capping module with L at position 24, and
wherein said N-terminal capping module comprises an amino acid sequence that has at least 70% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 37.
2. The protein according to claim 1, wherein said N-terminal capping module further has one or more of the following mutations:
(i) an amino acid residue selected from the group consisting of I, T, A, V, L and M at position 15;
(ii) an amino acid residue selected from the group consisting of R and K at position 19;
(iii) an amino acid residue selected from the group consisting of L, V and I at position 22; and
(iv) an amino acid residue selected from the group consisting of A and K at position 23.
3. The protein according to claim 1, wherein said N-terminal capping module comprises an amino acid sequence at positions 19 to 24 selected from the group consisting of: (R/K)(1/E)L(L/I/M)(A/K)L, RILMAL, RELLKL, RILLKL, RELIKL, RILIKL, RELLAL, RILLAL, RELIAL, RILIAL, KILMAL, KELLKL, KILLKL, KELIKL, KILIKL, KELLAL, KILLAL, KELIAL and KILIAL.
4. The protein according to claim 1, wherein said ankyrin repeat domain has a higher melting temperature than a reference ankyrin repeat domain having the same amino acid sequence except for the amino acid residue at position 24 of the N-terminal capping module, which is A in the reference ankyrin repeat domain.
5. The protein according to claim 1, wherein said protein comprises one or more further ankyrin repeat domains.
6. A nucleic acid comprising a sequence encoding the protein according to claim 1.
7. A cell comprising the nucleic acid according to claim 6.
8. A library of proteins comprising an ankyrin repeat domain, wherein the library comprises one or more proteins according to claim 1.
9. A method for selecting a protein that specifically binds to a target comprising the following steps:
(i) providing the library of proteins according to claim 8; and
(ii) selecting a protein specifically binding to the target via its ankyrin repeat domain from the library, wherein the selected protein is a protein comprising an ankyrin repeat domain, wherein the library comprises one or more proteins comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has an N-terminal capping module with L at position 24, and wherein said N-terminal capping module comprises an amino acid sequence that has at least 70% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 37.
10. A method of preparing a protein comprising the following steps (A) or (B):
(A) (i) selecting a protein comprising an ankyrin repeat domain with an N-terminal capping module that does not have L at position 24; and
(ii) replacing one or more amino acid residues of the protein to result in a protein according to claim 1 or
(B) designing or optimizing the amino acid sequence of an ankyrin repeat domain in silico through computational methods to result in a protein according to claim 1.
11. The method according to claim 9, wherein the resulting protein is further modified with one or more further moieties and/or with one or more further ankyrin repeat domains.
12. A method of producing a protein comprising the following steps:
(i) expressing or synthesizing
a protein comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has an N-terminal capping module with L at position 24, and wherein said N-terminal capping module comprises an amino acid sequence that has at least 70% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 37;
or
a protein resulting from the method comprising the steps of (a) selecting a protein comprising an ankyrin repeat domain with an N-terminal capping module that does not have L at position 24; and (b) replacing one or more amino acid residues of the protein to result in a protein comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has an N-terminal capping module with L at position 24, and wherein said N-terminal capping module comprises an amino acid sequence that has at least 70% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 37; or
a protein resulting from a method comprising the steps of designing or optimizing the amino acid sequence of an ankyrin repeat domain in silico through computational methods to result in a protein comprising an ankyrin repeat domain, wherein the ankyrin repeat domain has an N-terminal capping module with L at position 24, and wherein said N-terminal capping module comprises an amino acid sequence that has at least 70% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 37;
and
(ii) purifying the expressed or synthesized protein.
13. The method according to claim 12, further comprising the following step:
(ii) formulating the purified protein as a pharmaceutical composition.
16. The method of claim 10, wherein the resulting protein is further modified with one or more further moieties and/or with one or more further ankyrin repeat domains.
One well-known ankyrin repeat directed to CD40 with “improved pharmacokinetic properties” and improved binding affinity for CD40 was SEQ ID NO: 3 of US12331090 (3.4. CD40 Binding Domains).
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As is clear from the comparison above, SEQ ID NO: 3 is identical to SEQ ID NO: 18, 35 or 91 with I at position 15. Thus, the conflicting claims, in light of well-known ankyrin CD40 binding domains, clearly suggest the instant claims.
Prior Art
N-terminal capping in ankyrin repeat proteins to increase thermostability is known (WO 2021/116462). However, the specific claimed mutation of I at position 15 of SEQ ID NOS: 18, 35 or 91 is not known or suggested. Rather, only an L mutation at this position is taught (e.g. SEQ ID NO: 8 in WO 2021/116462).
Conclusion
No claims are allowed.
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/YUNG-SHENG M TSUI/ Primary Examiner, Art Unit 1684
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