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 Application, Amendments, and/or Claims
1. Claims 1, 3, 7-9, 11, 16-17, 19-20, 22-26, 28, and 30 are pending and currently under consideration.
Information Disclosure Statement
2. The information disclosure statement filed on 04/30/2024 has been considered by the Examiner and an initialed copy of the form PTO-1449 is attached to this communication.
Drawings
3. The drawings filed on 02/13/2024 are accepted by the examiner.
Claim Rejections[Symbol font/0xBE]35 USC § 112 (b)
4. The following is a quotation of the second paragraph of 35 U.S.C. 112:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 1, 11, and 28 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.
(i). Claim 1 recites “wherein the cytokine-receptor activating activity of the inducible cytokine prodrug is at least about 10X less than the cytokine receptor activating activity of the polypeptide that contains the cytokine polypeptide that is produced by cleavage of the protease cleavable linker”. The language of “at least about 10X less than” is ambiguous and fails to provide reasonable certainty as to the scope of the invention.
(ii). Claim 11 are indefinite because it recites “wherein the cytokine polypeptide comprises Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, or Compound 10, or an amino acid sequence variant of the foregoing”. The acronyms “Compound 1, Compound 2, Compound 3, Compound 4, Compound 5, Compound 6, Compound 7, Compound 8, Compound 9, and Compound 10” are determined arbitrarily without a definitive structure. Others in the field may prepare same molecule and give an entirely different name. Thus, reciting a biochemical molecule by a particular name given to the molecule by various workers in the field fails to distinctly indicating what the molecule is. Applicants should particularly point out and distinctly recite the protein by reciting characteristics associated with the molecule, such as a sequence identifier (SEQ ID NO).
(iii). Claim 28 recites the limitation, “wherein the antibody or antigen-binding fragment is a single domain antibody, a Fab, or a scFv that binds the IFN polypeptide”. There is insufficient antecedent basis for this limitation in the claim or in claim 1, from which it depends.
Claim Rejections under 35 USC § 103(a)
6. The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
7. Claims 1, 3, 7-9, 16-17, 19-20, 22-23, 25-26, and 30 are rejected under 35 U.S.C. 103(a) as being unpatentable over WO 2020/069398 A1 (02 April 2020).
WO 2020/069398 A1 teaches a combination composition comprising a prodrug for cancer therapy (page 6, paragraph [0036]) comprising a cytokine polypeptide, a blocking element, and a half-life extension element, which are operably linked by the protease-cleavable polypeptide linker (Fig. 1A; Abstract) and a PD-1 inhibitor (paragraph [0030]). The cytokine is an IL-2, an IL-15 polypeptide (page 3, paragraph [0011]), IFN-α, IFN-β, or IFN-γ (page 40, paragraph [0199]; page 43, paragraph [0203]). The half-life extension element is an immunoglobulin Fc domain (page 3, paragraphs [0015], [0027]), which would yield a prodrug comprising two polypeptide chains. The protease cleavable linker comprises a sequence that is capable of being cleaved by a protease, such as a matrix metalloproteinase (MMP) or an ADAM (page 3, paragraph [0023]). The masking moiety blocks or inhibits the activity or binding of the cytokine to its cognate receptor or protein (Abstract; page 49, paragraph [0225]).
WO 2020/069398 A1 does not explicitly teach an anti-PD-1 antibody or an anti-PD-L1 antibody as recited in claims 17 and 20.
However, anti-PD-1 antibodies and the anti-PD-L1 antibodies recited in claims 17 and 20 are well-known in the art and are used for cancer immune therapy. It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a combination composition comprising the prodrug taught by WO 2020/069398 A1 and an anti-PD-1 antibody/an anti-PD-L1 antibody with a reasonable expectation of success. One would have been motivated to do so because WO 2020/069398 A1 teaches a combination composition comprising a prodrug and a PD-1 inhibitor.
8. Claims 24 and 28 are rejected under 35 U.S.C. 103(a) as being unpatentable over WO 2020/069398 A1 (02 April 2020) as applied to claims 1, 3, 7-9, 16-17, 19-20, 22-23, 25-26, and 30 above, and further in view of US 2019/0367576 A1 (Pub. Date: Dec. 5, 2019).
WO 2020/069398 A1 teaches a combination therapy composition as applied to claims 1, 3, 7-9, 16-17, 19-20, 22-23, 25-26, and 30 above.
WO 2020/069398 A1 does not teach (i). a protease cleavable linker comprises a sequence that is capable of being cleaved by a protease selected from cathepsin B, cathepsin C, cathepsin D, cathepsin E, cathepsin K, cathepsin L, or cathepsin G as recited in claim 24; and (ii). a single domain antibody, Fab or scFv that binds the IFN polypeptide as recited in claim 28.
US 2019/0367576 A1 teaches protease-cleavable polypeptide linkers, where each protease-cleavable polypeptide linker independently comprises at least one sequence that is capable of being cleaved by cathepsin G or cathepsin L (paragraph [0012]). US 2019/0367576 A1 further teaches that the IL-12 blocking moiety can comprise a single domain antibody, Fab or scFv that binds the IL-12 polypeptide (paragraph [0013]).
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a prodrug comprising a protease cleavable linker comprises a sequence that is capable of being cleaved by cathepsin G or cathepsin L and to make an IFN blocking moiety comprising a single domain antibody, Fab or scFv that binds the IFN polypeptide with a reasonable expectation of success. One would have been motivated to do so because a protease cleavable linker comprising a sequence that is capable of being cleaved by cathepsin G or cathepsin L and a cytokine blocking moiety comprising a single domain antibody, Fab or scFv that binds the cytokine polypeptide are well-known in the art and routinely practiced in the field as demonstrated by US 2019/0367576 A1 above.
Claim Rejections[Symbol font/0xBE] Nonstatutory Obviousness-Type Double Patenting
9. Basis for nonstatutory 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. See 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 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/ guidance/eTD-info-I.jsp.
10. Claims 1, 3, 7-9, 11, 16-17, 19-20, 22-26, 28, and 30 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-21 of US Patent No. 12,076,371 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-21 of US Patent No. 12,076,371 B2 are drawn to a fusion polypeptide having the formula of: [D]-[L1]-[A]-[L2']-[H], wherein [A] is an interferon alpha (IFNa) polypeptide, a mutein, or an active fragment thereof, [D] is a blocking moiety, [H] is a half-life extension moiety, [L1] is a protease-cleavable polypeptide linker comprising the amino acid sequence of SEQ ID NO: 609, 612, or 615, and [L2'] is a protease-cleavable polypeptide linker comprising the amino acid sequence of SEQ ID NO: 609, 612, or 615, wherein the blocking moiety and the half-life extension moiety each independently comprise human serum albumin (HSA) or an antibody or antibody fragment that binds the HSA.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a combination composition comprising the prodrug and an anti-PD-1 antibody/an anti-PD-L1 antibody with a reasonable expectation of success. One would have been motivated to do so because anti-PD-1 antibodies and the anti-PD-L1 antibodies are well-known in the art and are used for cancer immune therapy.
11. Claims 1, 3, 7-9, 11, 16-17, 19-20, 22-26, 28, and 30 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-9, and 12 of US Patent No. 12,617,829 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-9, and 12 of US Patent No. 12,617,829 B2 are drawn to a conditionally active IL- 18 comprising a fusion polypeptide comprising at least one of each of a) A human IL-18 polypeptide [A]; b) an IL-18 blocking moiety [D], wherein the IL-18 blocking moiety [D] comprises an antibody or antigen-binding fragment that binds the IL-18 polypeptide, a ligand-binding domain or fragment of a cognate receptor for the IL-18 polypeptide; c) a half-life extension element [H], wherein the half-life extension element [H] is a human serum albumin, an antigen-binding polypeptide that binds serum albumin, or an immunoglobulin Fc; and d) a protease cleavable polypeptide linker [L]; wherein the conditionally active cytokine has attenuated IL-18 receptor activating activity that is at least about 10-fold less than the IL-18 receptor activating activity of the polypeptide that contains the IL-18 polypeptide that is produced by cleavage of the protease cleavable linker.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a combination composition comprising the prodrug and an anti-PD-1 antibody/an anti-PD-L1 antibody with a reasonable expectation of success. One would have been motivated to do so because anti-PD-1 antibodies and the anti-PD-L1 antibodies are well-known in the art and are used for cancer immune therapy.
12. Claims 1, 3, 7-9, 11, 16-17, 19-20, 22-26, 28, and 30 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-21 and 26-29 of US Patent No. 12,076,371 B2. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-21 and 26-29 of US Patent No. 12,076,371 B2 are drawn to a fusion polypeptide having the formula of: [D]-[L1]-[A]-[L2']-[H], wherein,[A] is an interferon alpha (IFNa) polypeptide, a mutein, or an active fragment thereof, [D] is a blocking moiety, [H] is a half-life extension moiety, [L1] is a protease-cleavable polypeptide linker comprising the amino acid sequence of SEQ ID NO: 609, 612, or 615, and [L2'] is a protease-cleavable polypeptide linker comprising the amino acid sequence of SEQ ID NO: 609, 612, or 615, wherein the blocking moiety and the half-life extension moiety each independently comprise human serum albumin (HSA) or an antibody or antibody fragment that binds the HSA.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a combination composition comprising the prodrug and an anti-PD-1 antibody/an anti-PD-L1 antibody with a reasonable expectation of success. One would have been motivated to do so because anti-PD-1 antibodies and the anti-PD-L1 antibodies are well-known in the art and are used for cancer immune therapy.
13. Claims 1, 3, 7-9, 11, 16-17, 19-20, 22-26, 28, and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 18/764,830. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-22 of copending Application No. 18/764,830 are drawn to a method of treating cancer in a subject comprising administering to the subject in need thereof: a pharmaceutical composition comprising a fusion polypeptide having the formula of: [D]-[L1]- [A]-[L2']-[H], wherein [A] is an interferon alpha (IFNa) polypeptide, a mutein, or an active fragment thereof, [D] is a blocking moiety; [H] is a half-life extension moiety; [L1] is a protease-cleavable polypeptide linker comprising the amino acid sequence of SEQ ID NO: 609, 612, or 615; and [L2'] is a protease-cleavable polypeptide linker comprising the amino acid sequence of SEQ ID NO: 609, 612, or 615; and a pharmaceutically acceptable carrier, wherein the blocking moiety and the half-life extension moiety each independently comprise human serum albumin (HSA) or an antibody or antibody fragment that binds the HSA.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a combination composition comprising the prodrug and an anti-PD-1 antibody/an anti-PD-L1 antibody with a reasonable expectation of success. One would have been motivated to do so because anti-PD-1 antibodies and the anti-PD-L1 antibodies are well-known in the art and are used for cancer immune therapy.
This is a provisional nonstatutory double patenting rejection.
14. Claims 1, 3, 7-9, 11, 16-17, 19-20, 22-26, 28, and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 16-17, 19, and 21-22 of copending Application No. 18/626,430. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-14, 16-17, 19, and 21-22 of copending Application No. 18/626,430 are drawn to a method for treating cancer, comprising administering to a subject in need thereof and effective amount of an inducible interleukin-2 (IL-2) prodrug, including Compound 1, Compound 2, Compound 3, or Compound 4, wherein the inducible IL-2 prodrug is administered systemically, is activated by cleavage by a protease that has higher activity in the tumor microenvironment than in other locations, and results in at least about 40- fold more cleavage of the inducible IL-2 prodrug in the tumor microenvironment compared with the circulation.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a combination composition comprising the prodrug and an anti-PD-1 antibody/an anti-PD-L1 antibody to treat cancer with a reasonable expectation of success. One would have been motivated to do so because anti-PD-1 antibodies and the anti-PD-L1 antibodies are well-known in the art and are used for cancer immune therapy.
This is a provisional nonstatutory double patenting rejection.
15. Claims 1, 3, 7-9, 11, 16-17, 19-20, 22-26, 28, and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-5, 8, 10, 22, 29, and 73-74 of copending Application No. 18/312,245. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1, 4-5, 8, 10, 22, 29, and 73-74 of copending Application No. 18/312,245 are drawn to a conditionally active IL-21 comprising a fusion polypeptide comprising at least one of each of a) a IL-21 polypeptide [A]; b) a IL-21 blocking moiety [D], wherein the IL-21 blocking moiety [D] comprises an antibody or antigen-binding fragment that binds the IL-21 polypeptide, a ligand-binding domain or fragment of a cognate receptor for the IL-21 polypeptide; c) a half-life extension element [H], wherein the half-life extension element [H] is a human serum albumin, an antigen-binding polypeptide that binds serum albumin, or an immunoglobulin Fc; and d) a protease-cleavable polypeptide linker [L];wherein the IL-21 polypeptide and the IL-21 blocking moiety are operably linked by the protease- cleavable polypeptide linker and the conditionally active IL-21 has attenuated IL-21 receptor activating activity is at least about 10-fold less than the IL-21 receptor activating activity of the polypeptide that contains the IL-21 polypeptide that is produced by cleavage of the protease-cleavable linker.
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a combination composition comprising the prodrug and an anti-PD-1 antibody/an anti-PD-L1 antibody to treat cancer with a reasonable expectation of success. One would have been motivated to do so because anti-PD-1 antibodies and the anti-PD-L1 antibodies are well-known in the art and are used for cancer immune therapy.
This is a provisional nonstatutory double patenting rejection.
Claim Objection
16. Claim 17 is objected to because it depends on a cancelled claim (claim 15).
Conclusion
17. No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/RUIXIANG LI/ Examiner, Art Unit 1674
September 4, 2026
