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 .
Election/Restrictions
Applicant’s election of Group X (claims 1-4, 10, 12-14, 27-30, 33, 36-42, 47-54, 59-64 and 66-67) in the reply filed on 08/03/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 1-4, 6-8, 10, 12-14, 16-20, 22-24, 27-30, 33, 36-64, 66-72, 75, 78-84, 91, 92, 94, and 95 are pending; claims 6-8, 16-20, 22-24, 43-46, 55-58, 68-72, 75, 78-84, 91-92 and 94-95 are withdrawn from prosecution for being drawn to non-elected subject matter. Claims 1-4, 10, 12-14, 27-30, 33, 36-42, 47-54, 59-64 and 66-67 as drawn to a method for treating a cancer, the method comprising administering to a subject in need thereof: i) a multispecific protein comprising a CD123 binding domain and a CD3 binding domain; and ii) a second anti-cancer agent, wherein the anti-cancer agent is a combination of azacitidine and venetoclax.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/19/2024 was considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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.
Claims 1-4, 10, 12-14, 37-42, 47-54, 59-64 and 66-67 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.
Specifically, in the independent claim 1, the recitation: a multispecific protein comprising a CD123 binding domain and a CD3 binding domain is indefinite because there is no indication of what the multispecific protein may also comprise.
As such, the metes and bounds of the claims could not be determined.
Claim 30 is 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. Line c) of the claim indicates that the CD123 binding domain is a scFv comprising a sequence of at least 90%, at least 95%, or 100% identical to SEQ ID NO: 27. According to the Sequence listing in the Specification, SEQ ID NO: 27 is anti-CD3 epsilon single chain antibody. Thus, it cannot be simultaneously anti CD3 antibody and anti CD123 antibody.
As such, the metes and bounds of the claims\ could not be determined.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 27-30, 33 and 36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). (emphasis added). See also MPEP 2163.04.
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is “had possession of the claimed subject matter as of the filing date. Demonstrating possession “requires a precise definition” of the invention. To provide this precise definition” for a claim to a genus, a patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen at page 1358).
In the instant case, the specification discloses methods of treatment that use the compound denominated TRI130 (SEQ ID NO: 312) which comprises a CD 123 binding domain comprising a VH of SEQ ID NO: 136 and a VL of SEQ ID NO: 134 and a CD3 binding domain comprising a VH of SEQ ID NO: 383 or 387 and a VL of SEQ ID NO: 384. However, the breadth of the claim comprises any VH of at least 90% identity with SEQ ID NO: 136 or SEQ ID NOs: 383 or 387, as well as any VL of at least 90% identity with SEQ ID NO: 134 or SEQ ID NO: 384, respectively, without indicating which part of the sequence is constant the VH or VL sequences. Given the approximate length of the sequences (~100-110 amino acids) the possible constructs would have 10 positions each that could be deleted or substituted with at least 19 natural amino acids and thus yielding an enormous number of compounds. For all this huge number, Applicant is in possession of one compound, TRI130.
When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. It is well-known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. taught that over hundreds of functional antibody fragments can be isolated from an antibody library that binds to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Protein Engineering, Design & Selection 2009, 22:159-168; see, e.g., Discussion).
Given the well-known high level of polymorphism of immunoglobulins / antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies and the unlimited number of antibodies encompassed by the claimed invention. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
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, 3, and 37-38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Davidson et al. (WO2020210277-cited by Applicant).
The reference disclosed a dosing regimen for administering a CD123 x CD3 bispecific diabody to patients with a hematologic malignancy such as acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), in combination with a molecule capable of binding PD-1 or a natural ligand of PD-L1 (abstract). The CD123 x CD3 bi specific diabody ( or pharmaceutical composition comprising the same) is used in combination with one or more additional therapeutic agent (e.g., therapeutic agents known to those skilled in the art for the treatment or prevention of a hematological malignancy, including but not limited to, current standard and experimental chemotherapeutic agents, hormonal agent, biological agent, immunotherapeutic agents, or agents useful for the mitigation of side effects of treatment) ([0126]). The CD123 x CD3 bispecific diabody and the other agent are administered to a human patient or other mammal in a sequence and within a time interval such that the CD123 x CD3 bispecific diabody and the other agent provide a desired therapeutic benefit. For example, each therapeutic agent (e.g., chemotherapeutic agent, hormonal agent or biological agent such as a molecule capable of binding PD-1) may be administered at the same time or sequentially in any order at different points in time; however, if not administered at the same time, they should be administered sufficiently close in time so as to provide the desired therapeutic or prophylactic effect. Each therapeutic agent can be administered separately, in any appropriate form and by any suitable route, e.g., one by the oral route and one parenterally, etc. ([0127]). Methods of administering include, but are not limited to, parenteral administration (e.g., intradermal, intramuscular, intraperitoneal, intravenous and subcutaneous) ([0129]). A bispecific antibody dose of 4µg/kg or lower was associated with the inhibition of tumor growth ([0093]).
As such, claims 1, 3, and 37-38 are anticipated by the reference cited.
Claims 1-4, 27-29, 37, 40, 63-64 and 66 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Saville et al. (U.S. Pub. No. 20170349660 – cited by Applicant).
The reference disclosed a method for treating a CD123-expressing cancer, e.g., a hematologic cancer, e.g., leukemia, in a human subject, comprising an intravenous dose of between about 1 ng/kg and about 800 ng/kg of a bispecific anti-CD123 x anti-CD3 antibody (e.g., XENP14045) once every 6-8 days for a time period sufficient to treat the CD123-expressing cancer. The treatment may be delivered monthly and may be extended to 9 weeks ([0009]-[0016]). The method further comprise administering a bispecific anti-CD123 x anti-CD3 antibody (e.g., XENP14045) described herein is administered to a subject who has AML, in combination with one or more of the following agents: Daunorubicin Hyrdochloride (e.g., Cerubidine or Rubidomycin) (optionally in combination with cytarabine and anthracycline-daunorubicin or idararubicin), Idarubicin Hydrochloride (e.g., Idamycin), BCL2 inhibitor (e.g., Venclextra), Cyclophosphamide (e.g., Cytoxan, Clafen, Neosar), Cytarabine (e.g., Cytosar-U, Tarabine PFS), Doxorubicin Hydrochloride, Decitabine (hypomethylating agent), azacitidine (e.g., Vidaza, hypomethylating agent), Vincristine Sulfate (e.g., Vincasar PFS).
As such, claims 1-4, 27-29, 37, 40, 63-64 and 66 are anticipated by the reference cited.
Claims 1-4, 13, 27-29, 37, 39, 40, 63-64 and 66-67 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Saville et al. (WO2019232528).
The reference disclosed methods for treating human subjects with bispecific anti-CD123 x anti-CD3 antibodies.
Administration may be performed in at least a first and a second phase, in
combination with at least one other therapeutic agent, where during the first phase, the
bispecific anti-CD123 x anti-CD3 antibody is administered to the human subject in an
amount of between about 700 ng/kg and about 1,900 ng/kg, once a week, for one or two weeks, and where during the second phase, the bispecific anti-CD123 x anti-CD3 antibody is administered to the human subject in an amount of between about 2,000 ng/kg and about 5,000 ng/kg, once a week, for at least one week. The at least one other therapeutic agent are administered over about two hours. The second phase has a duration of one or two weeks or is maintained until remission.
The method further comprises administering a maintenance dose, comprising the same amount of the bispecific anti-CD123 x anti-CD3 antibody and/or the at least one other therapeutic agent are administered in the second phase. The maintenance dose is administered once every two weeks for at least one dose or once every three or four weeks or once a month for at least one dose ([0008]-[0015]). The reference also teaches a third phase where the bispecific anti-CD123 x anti-CD3 antibody is administered to the human subject in an amount of between about 3,000 ng/kg and about 11,000 ng/kg, with at least one other therapeutic agent are administered over about two hours, once a week for at least one or two weeks and it may be followed by a maintenance phase/dose ([0016]-[0030]). The administration is performed by intravenous infusion or injection [0169]).
The bispecific anti-CD123 x anti-CD3 antibody is administered in combination with one or more therapeutic agents: daunorubicin HCl, idarubicin HCl, venetoclax, cyclophosphamide, cytarabine, doxorubicin HCl, decitabine, azacitidine or, decitabine, for treating a patient with AML ([0437]).
Thus, claims 1-4, 13, 27-29, 37, 39, 40, 63-64 and 66-67 are anticipated by the reference cited.
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 1-4, 13, 27-30, 33, 36-37, 39-40, 63-64 and 66-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3 and 6 of U.S. Patent No. 10, 676, 533 in view of Saville et al. (WO2019232528-Saville ‘528).
The claims of the U.S. Patent are drawn to a method for treating a disorder in a subject, wherein said disorder is characterized by overexpression of CD123, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a recombinant polypeptide comprising a CD123 binding domain and a CD3 binding domain; wherein the recombinant polypeptide comprises the amino acid sequence of SEQ ID NO:130 or SEQ ID NO:132; and wherein the administration of the pharmaceutical composition induces reduced cytokine levels in the subject as compared to administration of (a) a dual affinity re-targeting antibody comprising the CD123 binding domain and the CD3 binding domain of the recombinant polypeptide; or (b) a bispecific T-cell engager molecule comprising the CD123 binding domain and the CD3 binding domain of the recombinant polypeptide. The disorder is a cancer, acute myeloid leukemia (AML), B-lymphoid leukemia, blastic plasmocytoid dendritic neoplasm (BPDCN), hairy cell leukemia, acute lymphoblastic leukemia, refractory anemia with excess blasts, myelodysplastic syndrome, chronic myeloid leukemia or Hodgkin's lymphoma. The pharmaceutical composition comprises a dimeric protein comprising two identical copies of the recombinant polypeptide. The SEQ ID NO: 130 and 132 of the Patent comprise the CDR sequences claimed in the instant Application and the SEQ ID NO: 132 of the Patent is 97.5% identical with the SEQ ID NO: 31 (the sequence of the bispecific antibody claimed instantly). Thus, the properties of the Patent antibodies are the same antibodies as the instantly claimed antibodies. The Patent is silent about the dosages and the use of venetoclax and azacitidine. Saville ’528, as indicated supra, indicated the dosages and the use of venetoclax and azacitidine for treating cancers in combination with the CD123xCD3 bispecific antibodies. It would have been obvious for a person of ordinary skill in the art to use the antibodies of the U.S. Patent in the methods of Saville’528 with a reasonable expectation of success.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/ Primary Examiner, Art Unit 1647
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