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 .
Claims 1-16 are pending and examined on merits.
Claim Objections
Claims 5 and 8 are objected to because of the following informalities: The claims are drafted using Markush language but the syntax is not in an accepted format. MPEP 2117 discusses accepted formats are “a material selected from the group consisting of A, B, and C” or “wherein the material is A, B, or C”. Appropriate correction is required.
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.
Claim 1-8 and 12-16 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 1-7 and 12-16 recite “a signaling and/or targeting domain’ directly or through their claim dependency. The phrase can be broken down into three: (1) a signaling domain, (2) a targeting domain, and (3) a signaling and a targeting domain”. Claim 5 recites various antibodies as Markush group members. Claims 5 defines the recited Markush members as being (1) a signaling domain, (2) targeting domain, and (3) a signaling and targeting domain”. However, the definition in claim 5 is contradictory to the definition of a signaling and targeting domain in the specification copied below. Amending claim 5 to indicate those Markush members being a targeting domain would obviate this rejection.
The specification as originally filed discloses:
[0165] As used herein, the term “signaling domain” refers to a domain that binds a surface molecule and initiates an intracellular signal transduction cascade. The ‘signaling domain’ is composed of monomeric, dimeric (e.g. homodimeric or heterodimeric) or trimeric (e.g. homotrimeric or heterotrimeric) proteins of the TNF family and possesses agonistic properties to stimulate the activation of different immune cell types.
[0082] As used herein, the term “targeting domain” refers to a domain having functions of recognition and anchoring of on the surface of specific cells in tissues or organs of interest. The targeting domain of the present invention recognizes a marker on the surface of specific cells, for instance tumor cells or immune cells; this anchors and displays the TAME-IT molecule on the cell surface and may signal inside the targeted cells. The targeting domain of the present invention also can block a signal by competition.
Claims 3 and 4 are also rejected because they have the same scope. Amending the scope of either claim 3 or 4 would obviate this rejection.
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 1-16 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.
Claims 1-16 encompass a broad genus of fusion proteins and their use in methods of treating cancer and various other diseases in claims 13 and 14. The claimed genus of fusion proteins has three parts: (1) a genus of targeting domain; (2) a genus of linkers; (3) a genus of signal domains.
The disclosure of the specification is limited to “TAME-IT’ which is same as KN035-TAA-th4-1BB, KN035 being an anti-PD-L1 nanobody and th4-1BBL a trimeric human 4-1BBL domain. The structure of the linker portion of TAME-IT is not disclosed. As for treatment of the diseases, the disclosure is limited to the treatment of cancer. The TAME-IT protein enhances the activation of CD8 T cells and the killing of melanoma cells (Fig. 7A). The specification does not disclose a combination of 1) a genus of targeting domain; (2) a genus of linkers; (3) a genus of signal domains for the treatment of disease listed in claims 13 and 14.
The level of skill and knowledge in the art would not be able to make even “TAME-IT” since the linker portion of “TAME-IT” is n not disclosed, let alone making fusion protein able to treat the diseases in claims 13 and 14.
Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession the claimed genus except those art-known product for cancer treatment (see below under art rejection). Applicant had possession of TAME-IT but the structure of TAA is not disclosed in the specification.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (MPEP 2163).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC 2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
Scope of Enablement
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for cancer treatment using the art-known chimeric proteins (see art rejection below), does not reasonably provide enablement for any other claimed subgenus of chimeric products for treating disease listed in claims 13 and 14. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
Breadth of claims and nature of invention:
Claims 1-16 encompass a broad genus of fusion proteins and their use in methods of treating cancer and various other diseases in claims 13 and 14. The claimed genus of fusion proteins has three parts: (1) a genus of targeting domain; (2) a genus of linkers; (3) a genus of signal domains.
Amount of direction and existence of working examples:
The specification teaches “TAME-IT’ which is same as KN035-TAA-th4-1BBL molecule, KN035 being an anti-PD-L1 nanobody and th4-1BBL a trimeric human 4-1BBL domain. The TAME-IT protein enhances the activation of CD8 T cells and the killing of melanoma cells killing of melanoma cells T. (Fig. 7A) and results section. The specification does not teach any other chimeric proteins. The disclosure of the specification is limited to cancer treatment using cancer targeting antibodies.
Level of predictability, state of prior art, and quantity of experimentation needed:
WO 2019094574 A1teaches a fusion protein comprising an antibody targeting a cancer antigen (targeting domain)-liner (Fc)-TNF family signal domain. The fusion protein is used to treat cancer.
KANG ET AL (see full citation on 892) teaches Meso scFv-O-Fc and Meso scFv-ROR-Fc comprising an antigenic peptide as a linker linking a targeting domain and Fc domain. The chimeric protein has a mesothelin (Meso) scFv and an Fc domain as a targeting domain and an antigenic peptide (SIINFEKL) as a linker.
US-20210221904 (thereinafter “ZURAWSKI”) teaches:
[0146] In one aspect, the one or more of the antigenic peptides are selected from at least one of: Nef (66-97): VGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGL (SEQ ID NO.: 1); Nef (116-145): HTQGYFPDWQNYTPGPGVRYPLTFGWLYKL (SEQ ID NO.: 2); Gag p17 (17-35): EKIRLRPGGKKKYKLKHIV (SEQ ID NO.: 3); Gag p17-p24 (253-284): NPPIPVGEIYKRWIILGLNKIVRMYSPTSILD (SEQ ID NO.: 4); or Pol 325-355 (RT 158-188) is: AIFQSSMTKILEPFRKQNPDIVIYQYMDDLY (SEQ ID NO.: 5). In one aspect, the fusion protein peptides are separated by one or more linkers selected from: SSVSPTTSVHPTPTSVPPTPTKSSP (SEQ ID NO.: 11); PTSTPADSSTITPTATPTATPTIKG (SEQ ID NO.: 12); TVTPTATATPSAIVTTITPTATTKP (SEQ ID NO.: 13); or TNGSITVAATAPTVTPTVNATPSAA (SEQ ID NO.: 14).
ZURAWSKI teaches when a fusion protein is claimed with new linkers, the new linker sequences are described in detail.
Thus, one of skilled in the art would expect a TAA or other linkers not well known in the art to be disclosed in a specification.
Further, one of skilled in the art would not able to make the claimed chimeric proteins using TAA or tolerance antigen to treat the various diseases in claims 13 and 14, given the disclosure of the specification is limited to cancer treatment.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-5, 8, 12, and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2019094574 A1 (hereinafter “Mumm”, which was cited on the search report, therefore a copy not provided with this Office action).
Regarding claims 1 and 2, drawn to a nucleic acid encoding a chimeric protein or the chimeric protein comprising targeting/signaling domain - linker - targeting/signaling domain, in either order, Mumm at Fig. 2 teaches BFP2 and BFP3 and Example 1.
Regarding claims 3 and 4, drawn to the signaling and/or targeting domain (a) is monomeric, homodimeric, heterodimeric, homotrimeric or heterotrimeric, Mumm teaches momomeric and homotrimeric and other oligmoeric forms of the signaling and/or targeting domain, for example CD40L. Note para [0099] through [00109].
Regarding claims 5, 8, 12, and 15, drawn to anti-PD-L1, signaling domains, method of treating cancer using the chimeric construct, and a vector, Mumm teaches anti-PD-L1 antibody linked to OX40L. Note Example Nos 17 and 20 and Para [00194], Anti-PD-Ll+CD40L FPs BFP2 and BFP3 see Table 1 on page 23, also note [00177] for a vector.
Claim(s) 1-5, 8, 12, and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by TAE HEUNG KANG ET AL, "Targeted Coating With Antigenic Peptide Renders Tumor Cells Susceptible to CD8+ T Cell-mediated Killing", MOLECULAR THERAPY, vol. 21, no. 3, 27 November 2012, pages 542-553, XP055275048 cited on form 237 (Written Opinion).
.
KANG ET AL, teaches the following chimeric proteins with a linker as shown below.
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Meso scFv-O-Fc and Meso scFv-ROR-Fc above comprising an antigenic peptide as a linker linking a targeting domain and Fc domain (signaling/targeting domain since its binding to its receptor). The chimeric protein targets Meso- expressing tumor cells and enables antigen presentation, resulting in tumor clearance by preexisting antigen-specific CD8 T cells (refer to abstract; Fig. 1, 3, 4).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mumm as applied to claims 1-5, 8, 12, and 15 above, and further in view of US 10836808 B2.
Mumm does not teach the cells recited in claim 16.
However, US 10836808 B2 teaches the following:
(567) In some cases, a nucleic acid comprising a nucleotide sequence encoding a chimeric Notch receptor polypeptide of the present disclosure is a recombinant expression vector. In some embodiments, the recombinant expression vector is a viral construct, e.g., a recombinant adeno-associated virus (AAV) construct, a recombinant adenoviral construct, a recombinant lentiviral construct, a recombinant retroviral construct, etc. In some cases, a nucleic acid comprising a nucleotide sequence encoding a chimeric Notch receptor polypeptide of the present disclosure is a recombinant lentivirus vector. In some cases, a nucleic acid comprising a nucleotide sequence encoding a chimeric Notch receptor polypeptide of the present disclosure is a recombinant AAV vector.
(568) Suitable expression vectors include, but are not limited to, viral vectors (e.g. viral vectors based on vaccinia virus; poliovirus; adenovirus (see, e.g., Li et al., Invest Opthalmol Vis Sci 35:2543 2549, 1994; Borras et al., Gene Ther 6:515 524, 1999; Li and Davidson, PNAS 92:7700 7704, 1995; Sakamoto et al., Hum Gene Ther 5:1088 1097, 1999; WO 94/12649, WO 93/03769; WO 93/19191; WO 94/28938; WO 95/11984 and WO 95/00655); adeno-associated virus (see, e.g., Ali et al., Hum Gene Ther 9:81 86, 1998, Flannery et al., PNAS 94:6916 6921, 1997; Bennett et al., Invest Opthalmol Vis Sci 38:2857 2863, 1997; Jomary et al., Gene Ther 4:683 690, 1997, Rolling et al., Hum Gene Ther 10:641 648, 1999; Ali et al., Hum Mol Genet 5:591 594, 1996; Srivastava in WO 93/09239, Samulski et al., J. Vir. (1989) 63:3822-3828; Mendelson et al., Virol. (1988) 166:154-165; and Flotte et al., PNAS (1993) 90:10613-10617); SV40; herpes simplex virus; human immunodeficiency virus (see, e.g., Miyoshi et al., PNAS 94:10319 23, 1997; Takahashi et al., J Virol 73:7812 7816, 1999); a retroviral vector (e.g., Murine Leukemia Virus, spleen necrosis virus, and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus, avian leukosis virus, a lentivirus, human immunodeficiency virus, myeloproliferative sarcoma virus, and mammary tumor virus); and the like. In some cases, the vector is a lentivirus vector. Also suitable are transposon-mediated vectors, such as piggyback and sleeping beauty vectors.
(569) Host Cells
(570) The present disclosure provides host cells genetically modified with a nucleic acid of the present disclosure, i.e., host cells genetically modified with a nucleic acid comprising a nucleotide sequence encoding a chimeric Notch receptor polypeptide of the present disclosure. The present disclosure provides a method of modulating an activity of a cell that expresses a chimeric Notch polypeptide of the present disclosure. The method generally involves contacting the cell with a second member of the specific binding pair. Binding of the first member of the specific binding pair to the second member of the specific binding pair induces cleavage of the Notch receptor polypeptide at the one or more ligand-inducible proteolytic cleavage sites, thereby releasing the intracellular domain. Release of the intracellular domain modulates an activity of the cell.
(571) In some cases, the cell is a eukaryotic cell. In some cases, the cell is a mammalian cell, an amphibian cell, a reptile cell, an avian cell, or a plant cell. In some cases, the cell is a plant cell.
(572) In some cases, the cell is a mammalian cell. In some cases, the cell is a human cell. In some cases, the cell is a mouse cell. In some cases, the cell is rat cell. In some cases, the cell is non-human primate cell. In some cases, the cell is lagomorph cell. In some cases, the cell is an ungulate cell.
Therefore one of ordinary skill in the art would have been able to use the art known cells to express the claimed chimeric protein with a reasonable expectation of success.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Misook Yu whose telephone number is (571)272-0839. The examiner can normally be reached M-Th, 7-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, YVONNE (BONNIE) EYLER can be reached at (571)272-1200. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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