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
Acknowledgement is hereby made of receipt and entry of the communication filed on Aug. 15, 2024. Claims 22-39 are pending and currently examined.
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 22-39 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.
This rejection has the following grounds.
A. Base claims 22, 28 and 34 recite “a variant Ig Fc polypeptide” which renders the claims indefinite. The Specification does not clearly and exclusively define the phrase “a variant Ig Fc polypeptide”. It is known in the art what an Ig Fc polypeptide refers to (It consists of the Ig heavy chain constant domains and interacts with immune cell Fc receptors). However, it is not clear how to interpret “a variant” of an Ig Fc polypeptide. E.g., it is not clear what structural and/or functional features a polypeptide must have for it to be called “a variant Ig Fc polypeptide”.
B. Base claims 22, 28 and 34 recite “wherein the one or more immunomodulatory polypeptides comprise one or more variant interleukin-2 (IL-2) polypeptides comprising an amino acid sequence having 1-5 amino acid substitutions relative to the amino acid sequence set forth in SEQ ID NO: 15”. This limitation is not clear because it is not clear how the “one or more variant interleukin-2 (IL-2) polypeptides” is related with SEQ ID NO: 15. E.g., the limitation does not make it clear if the “variant interleukin-2 (IL-2) polypeptide” comprises a sequence identical to SEQ ID NO: 15 except for 1-5 amino acid substitutions, or not.
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 of this title, 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.
Claims 22, 24-28, 30-34 and 36-39 are rejected under 35 U.S.C. 103 as being unpatentable over Seidel et al. (US 2017/0058015 A1, published on March 2, 2017, also published as WO 2015/195531 A2 on Dec. 23, 2015; submitted in IDS filed on Jan. 24, 2023), in view of Johannsen et al. (The Journal of Immunology, 2010, 185: 3445–3455; submitted in IDS filed on May 2, 2024), Linard et al. (The Journal of Immunology, 2002, 168: 4802–4808; submitted in IDS filed on May 2, 2024), and/or Terashima et al. (Cancer Immunol Immunother (2014) 63:479–489; submitted in IDS filed on May 2, 2024), and further in view of Umana et al. (US 2016/0175397 A1, published on Jun. 23, 2016; submitted in IDS filed on May 2, 2024) and Gillies et al. (US 7186804 B2, date of patent March 6, 2007; submitted in IDS filed on May 2, 2024).
The base claims 22, 28 and 34 directed to a heterodimer comprising:
a) a first polypeptide comprising:
i) a peptide comprising a peptide epitope of a length of from 8 amino acids to 16 amino acids present in a cancer-associated antigen; and
ii) a b2-microglobulin (b2M) polypeptide class I MHC polypeptide; and
b) a second polypeptide comprising
i) an MHC class I heavy chain polypeptide, and
ii) a variant Ig Fc polypeptide,
wherein the first and/or the second polypeptide comprises one or more immunomodulatory polypeptides,
wherein the first and/or the second polypeptide comprises one or more linkers joining the components of the first and/or second polypeptides,
wherein the b2M polypeptide and MHC class I heavy chain polypeptide form a peptide/MHC complex with the cancer-associated antigen peptide epitope, and wherein the peptide/MHC complex of the multimeric polypeptide is capable of binding to the TCR of a CD8+ T cell,
wherein the one or more immunomodulatory polypeptides comprise one or more variant interleukin-2 (IL-2) polypeptides comprising an amino acid sequence having from 1-5 amino acid substitutions relative to the amino acid sequence set forth in SEQ ID NO:15,
wherein at least one of the variant IL-2 polypeptides (i) binds to an IL-2 receptor (IL2R) comprising alpha, beta, and gamma polypeptides having amino acid sequences set forth in SEQ ID NOs:16-18, and (ii) exhibits reduced binding affinity to the IL2R compared to the binding affinity of a control IL-2 polypeptide comprising the IL-2 amino acid sequence set forth in SEQ ID NO:15 for the IL2R, and wherein, when bound to a cytotoxic CD8+ T cell, the multimeric polypeptide causes an increase in the cytotoxic activity of the CD8+ T cell and/or the number of CD8+ T cells.
Claims 22, 28 and 34 specify three different cancer-associated antigens, i.e., NY-ESO-1, Ras, and WT-1, respectively.
Fig. 1 of the instant specification appears to present some relevant embodiments of the claimed invention with generic MOD ("immunomodulatory polypeptide", see PGPub [0020]) and epitope:
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It is noted that the claims recite a variant Ig Fc without specifying what the “variant” is relative to. Since Fc sequences of different Igs may be different, any Fc peptide of a specific Ig molecule may be considered as a variant relative to another Fc that differs in amino acid sequence.
Seidel teaches a heterodimer polypeptide comprising: a) a first polypeptide containing, from N- to C-terminus, (a leader), a peptide epitope (PEPTIDE), a linker L1, a first MHC polypeptide (B2M), a linker L2 and a MOD effector molecule (MOD), and b) a second polypeptide containing, from N- to C-terminus, (a leader), a second MHC polypeptide (HC), a linker L3, an Fc domain (Fc), a linker L4 and a TM domain. See e.g. Fig. 3A and 3B shown below:
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The regions designated “B2M” and “MHC-HC” are considered as MHC polypeptides.
Seidel teaches that embodiments for the epitope peptide can be epitope peptides from a virus or a tumor antigen (e.g., TUM or IGRP) and that embodiment for the immune modulatory polypeptides (MOD) can be various immune modulatory factors such as CTLA4, PD1, ICOS, OX40, CD20, and 4-lBB, among others. See e.g., Figures 34 C-H and paragraph [0124], [139-141] and [0376]. Seidel teaches that the disclosure provides a method of treating a cancer by stimulating a T cell clone which recognizes an epitope peptide on a cancer comprising contacting a T cell of the clone with a recombinant peptide described therein, wherein the recombinant peptide comprises the epitope peptide and comprises a T cell modulatory domain which is a stimulatory domain, in an amount effective to treat the cancer. See e.g. [0030]
Accordingly, Seidel teaches a heterodimer and a method of treating cancer with the heterodimer, wherein the heterodimer comprises: a) a first polypeptide comprising: i) a peptide comprising an epitope present in a cancer-associated antigen; and ii) first class I major histocompatibility complex (MHC) polypeptide; and b) a second polypeptide comprising a second class I MHC polypeptide, wherein the first and/or the second polypeptide comprises one or more immunomodulatory polypeptides (MOD), wherein the first class I MHC polypeptide is a 2-microglobulin polypeptide and the second class I MHC polypeptide is an MHC class I heavy chain (HC) polypeptide, wherein the second polypeptide comprises a variant Ig Fc polypeptide, wherein the first and second polypeptide form a heterodimer.
However, Seidel is silent on whether the epitope peptide comprised in the first polypeptide can be from the cancer-associated antigen NY-ESO-1, Ras or WT-1, and whether the immune modulatory polypeptide (MOD) can be a variant IL-2 polypeptide, as claimed.
Johannsen teaches that an attractive treatment of cancer consists inducing tumor-eradicating CD8+ CTL specific for tumor-associated Ags, such as NY-ESO-1 (ESO), a strongly immunogenic cancer germ line gene-encoded tumor-associated Ag, widely expressed on diverse tumors. To establish optimal priming of ESO-specific CTL and to define critical vaccine variables and mechanisms, the authors used HLA-A2/DR1 H-22/2 transgenic mice and sequential immunization with immunodominant DR1- and A2-restricted ESO peptides. Immunization of mice first with the DR1-restricted ESO123–137 peptide and subsequently with mature dendritic cells (DCs) presenting this and the A2-restriced ESO157–165 epitope generated abundant, circulating, high-avidity primary and memory CD8+ T cells that efficiently killed A2/ESO157–165+ tumor cells. This prime boost regimen was superior to other vaccine regimes and required strong Th1 cell responses, co-presentation of MHC class I and MHC class II peptides by the same DC, and resulted in upregulation of sphingosine 1-phosphate receptor 1, and thus egress of freshly primed CD8+ T cells from the draining lymph nodes into circulation. This well-defined system allowed detailed mechanistic analysis, which revealed that 1) the Th1 cytokines IFN-g and IL-2 played key roles in CTL priming, namely by upregulating on naive CD8+ T cells the chemokine receptor CCR5; 2) the inflammatory chemokines CCL4 (MIP-1b) and CCL3 (MIP-1a) chemoattracted primed CD4+ T cells to mature DCs and activated, naive CD8+ T cells to DC–CD4 conjugates, respectively; and 3) blockade of these chemokines or their common receptor CCR5 ablated priming of CD8+ T cells and upregulation of sphingosine 1-phosphate receptor 1. These findings provide new opportunities for improving T cell cancer vaccines. See Abstract.
Linard teaches that Ags derived from commonly mutated oncogenic proteins seem ideally suited as targets for tumor immunotherapy. The authors identified a N-ras mutation (a glutamine-to-arginine exchange at residue 61 (Q61R)), detected in a melanoma lesion, which was recognized specifically by the autologous TIL in the HLA-A*0101 context. The ras peptide 55–64Q61R was the epitope of these TIL and was regularly presented by Q61R-mutated HLA-A*0101+ melanoma cell lines. This peptide and its wild-type homolog (55–64wt) bound to HLA-A*0101 with similar affinities. However, only the mutated peptide could induce specific CTL expansion from PBL. See Abstract. Linard further teaches that their results from animal cancer models and recent observations in humans supporting a correlation between the presence of CTL specific for unique tumor mutations and good survival rate suggest that HLA class I-restricted mutated epitopes might be the best Ags to target. In this respect, oncogenic mutations may be especially good target Ags, as far as CTL killing of tumor cells expressing the oncogene would lead to a direct tumor growth disadvantage, even if Ag loss variant tumor cells are not eradicated. See page 4807, right column.
Terashima teaches that recent technical advances have enabled the identification of cytotoxic T lymphocyte (CTL) epitopes in various tumor-associated antigens (TAA s). The authors examined the expression of 17 kinds of TAA in 9 pancreatic cancer cell lines and 12 pancreatic cancer tissues. CTL responses to 23 epitopes derived from these TAA s were analyzed using enzyme-linked immunospot (ELISPOT), CTL, and tetramer assays in 41 patients, and factors affecting the immune responses were investigated. Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAA s, namely, MAGE -A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines. The frequency of lymphocyte subsets correlated well with TAA -specific immune response. Overall survival was significantly longer in patients with TAA -specific CTL responses than in those without. P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA -specific CTLs may improve the prognosis of these patients. See Abstract.
Accordingly, teachings of Johannsen, Linard and Terashima indicate the potential of cancer-associated antigens NY-ESO-1, Ras and WT-1 as immunotherapy targets for cancer therapy, and immunodominant peptide epitopes (e.g. ESO123-137 and ESO157-165 for NY-ESO-1) as antigen peptides presented by MHC/HLA for induction of antigen specific CD8+ CTLs as a cancer vaccine.
Umana teaches an invention relating to a combination therapy of specific tumor-targeted IL-2 variant immunocytokines with specific antibodies which bind human PD-L1. See Abstract. It specifically teaches that an IL-2 mutant, particularly a mutant of human IL-2, having reduced binding affinity to the a-subunit of the IL-2 receptor (as compared to wild-type IL-2, e.g. human IL-2 shown as SEQ ID NO: 2), such as an IL-2 comprising: i) one, two or three amino acid substitution(s) at one, two or three position(s) selected from the positions corresponding to residues 42, 45 and 72 of human IL-2 shown as SEQ ID NO:2, for example three substitutions at three positions, for example the specific amino acid substitutions F42A, Y45A and L72G; or ii) the features as set out in i) plus an amino acid substitution at a position corresponding to residue 3 of human IL-2 shown as SEQ ID NO:2, for example the specific amino acid substitution T3A; or iii) four amino acid substitutions at positions corresponding to residues 3, 42, 45 and 72 of human IL-2 shown as SEQ ID NO:2, for example the specific amino acid substitutions T3A, F42A, Y45A and L72G. See e.g. [0020-0023]. Umana teaches that as described in WO 2012/146628, an IL-2 mutant polypeptide with reduced binding to the a-subunit of the IL-2 receptor has a reduced ability to induce IL-2 signaling in regulatory T cells, induces less activation-induced cell death (AICD) in T cells, and has a reduced toxicity profile in vivo, compared to a wild-type IL-2 polypeptide. See e.g. [0259].
Gillies teaches an invention about fusion proteins comprising a non-IL-2 moiety fused to a mutant IL-2 moiety, where the fusion protein exhibits a greater selectivity than a reference protein including the non-IL-2 moiety fused to a non-mutant IL-2 moiety, and where the selectivity is measured as a ratio of activation of cells expressing IL-2RC receptor relative to activation of cells expressing IL-2R receptor. See e.g. columns 1 and 2. Gillies teaches that mutation of several amino acids within the IL-2 moiety of an Ig-IL2 fusion protein leads to reduced toxicity while having relatively little effect on the potency of the fusion protein in the treatment of various diseases. For instance, the extent to which the affinity of an IL-2 fusion protein variant for its receptors may be altered is a function of how well the particular fusion protein is concentrated at its intended target site. It is particularly useful to mutate one or more of the following amino acids within the IL-2 moiety: Lys8, Gln13, Glu15, His16, Leu19, Asp20, Gln22, Met23, Asn26, Arg38, Phe-2, Lys43, Thr51, His79, Leu80, Arg81, Asp84, ASn 88, Val91, Ile92, and Glu95. It is also useful to mutate one or more of the following amino acids within the IL-2 moiety: Leu25, Asn31, Leu40, Met46, Lys48, Lys49, Asp109, Glu110, Alal 12, Thr113, Val115, Glu116, Asn119, Arg120, Ile122, Thr123, Gln126, Ser127, Ser130, and Thr131. See para bridging columns 10 and 11.
Accordingly, both Umana and Gillies teach applications of affinity reduced IL-2 variant with the claimed mutations in tumor targeting therapies with advantages of reduced toxicity effects.
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to combine the teachings of Seidel, Johannsen, Linard, Terashima, Umana and Gillies to arrive at the invention as claimed. One would have been motivated to do so, e.g., to present an antigenic peptide of cancer-associated antigen NY-ESO-1, Ras or WT-1, taught in Johannsen, Linard, and Terashima (in place of the TUM peptide) as well as incorporating the IL-2 variant with reduced IL2R affinity as taught in Umana/Gillies (in place of a cytokine MOD) in the heterodimer MHC I fusion construct of Seidel so that the anti-tumor functions of these cancer-associated antigen peptides and IL-2 variant can be tested in the setting of the heterodimer MHC I fusion construct of Seidel. There is a reasonable expectation of success that such as construct can be made based on routine molecular biological procedures.
Umana and Gillies are silent on if the human IL-2 variant has a reduced binding affinity to an IL2R comprising SEQ ID NOs: 16-18 as the three subunits. However, the human IL-2 variants disclosed have indistinguishable structural characteristics as those claimed. It would have been reasonable to expect that they have the same IL2R binding properties as claimed. The Office does not have the facilities and resources to provide the factual evidence needed in order to establish that the human IL-2 variants having reduced binding affinity to an IL2R do not have an IL2R binding affinity as claimed. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed IL-2 variant is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claims 24, 30 and 36, the recited HLA-A heavy chain sequences are known at the time of invention. E.g., SEQ ID NO: 53 is identical to a human MHC class I antigen disclosed in GenBank: ALM96677.1.
Claims 23, 29 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Seidel et al. (US 2017/0058015 A1, published on March 2, 2017, also published as WO 2015/195531 A2 on Dec. 23, 2015; submitted in IDS filed on May 2, 2024), in view of Johannsen et al. (The Journal of Immunology, 2010, 185: 3445–3455; submitted in IDS filed on May 2, 2024), Linard et al. (The Journal of Immunology, 2002, 168: 4802–4808; submitted in IDS filed on May 2, 2024), Terashima et al. (Cancer Immunol Immunother (2014) 63:479–489; submitted in IDS filed on May 2, 2024), Umana et al. (US 2016/0175397 A1, published on Jun. 23, 2016; submitted in IDS filed on May 2, 2024) and Gillies et al. (US 7186804 B2, date of patent March 6, 2007; submitted in IDS filed on May 2, 2024), as applied above, and further in view of W. R. Strohl. (Current Opinion in Biotechnology 2009, 20:685–691; submitted in IDS filed on May 2, 2024).
Claims 23, 29 and 35 further specify that the variant Ig Fc polypeptide is a variant of a human IgG1 Fc polypeptide that comprises one or more amino acid substitutions selected from the group consisting of N297A, L234A, L235A, L234F, L235E, P331S and combinations thereof, wherein N297, L234, L235, and P331 correspond to amino acids 77, 14, 15, and 111, respectively, of the amino acid sequence set forth in SEQ ID NO:212.
Relevance of Seidel, Johannsen, Linard, Terashima, Umana and Gillies is set forth above. However, they are silent on if the Fc in the fusion construct is a variant of a human IgG1 Fc with the claimed sequence characteristics.
Strohl reviews optimization of Fc-mediated effector functions of monoclonal antibodies. It discloses the mutations of N297A, L234A, L235A, L234F, L235E and P331S, as claimed, in human IgG1, and that these mutations have the functions of decreasing antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and/or cytokine storm. See e.g. Table 2.
It would have been prima facie obvious for one of ordinary skill in the art at the time of invention to introduce the mutations disclosed in Strohl into the Fc region of Seidel in the fusion construct. One would have been motivated to do so, e.g., to decrease the effect of the Fc domain in ADCC, ADCP, CDC, and/or cytokine storms, as taught in Strohl.
Double Patenting Rejection
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 claims at issue 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 reference 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. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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/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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 22-39 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 36-55 of US application 18891753 in view of the prior art references cited in the art rejections above, and McKenna et al. (US 2004/0022760 A1, published on Feb. 5, 2004).
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass a heterodimer comprising: a) a first polypeptide comprising 1) a disease-associated peptide epitope, and 2) a first MHC I polypeptide B2M; b) a second polypeptide comprising a second MHC polypeptide which is a MHC I heavy chain polypeptide; and c) at least one immunomodulatory polypeptide (MOD); and wherein the first or the second polypeptide comprises an Ig Fc polypeptide.
The differences between the two sets of claims include: 1) the instant claims specify that the immunomodulatory polypeptide (MOD) be a variant IL-2 polypeptide while the reference claims recite a generic MOD; 2) the instant claims specify cancer-associated antigens NY-ESO-1, Ras or WT-1, while the reference claims specify antigens NY-ESO-1 (claims 36-40), a melanoma-associated antigen (MAGE) (claims 41-45), a peptide epitope presented by a coronavirus-encoded polypeptide (claims 46-50), and a peptide epitope presented by a cytomegalovirus-encoded polypeptide (claims 51-55); 3) while the instant claims are silent, the reference claims specify a first and a second disulfide bounds between Cys residues.
Regarding difference 1), both Umana and Gillies, cited in the 103 rejections above, teach applications of affinity reduced IL-2 variant with the claimed mutations in tumor targeting therapies with advantages of reduced toxicity effects; regarding difference 2), Johannsen, Linard, and Terashima, cited in the 103 rejections above, teach cancer-associated antigen NY-ESO-1, Ras or WT-1, while McKenna teaches various antigens, including antigens of melanoma, coronavirus and cytomegalovirus (see Table 1); and regarding difference 3), Seidel, cited in the 103 rejections above, teaches various disulfide bounds formed between Cys residues that link the MHC I polypeptides, including those specified in the reference claims (see throughout the specification of Seidel). One of skill in the art would have found it obvious to arrive at the instant claims from the reference claims, and vice versa, in view of the teachings the cited prior art references, which remedy the differences between the two sets of claims.
Therefore, claims 22-39 are obvious over claims 36-55 of US application 18891753, and vice versa.
Claims 22-39 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4 of US patent 11878062 in view of the prior art references cited in the art rejections above.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims encompass a heterodimer comprising: a) a first polypeptide comprising 1) a disease-associated peptide epitope, and 2) a first MHC I polypeptide B2M; b) a second polypeptide comprising a second MHC polypeptide which is an MHC I heavy chain polypeptide; and c) at least one immunomodulatory polypeptide (MOD); and wherein the first or the second polypeptide comprises an Ig Fc polypeptide.
The differences between the two sets of claims include: 1) the instant claims specify that the immunomodulatory polypeptide (MOD) be a variant IL-2 polypeptide while the reference claims specify 2 variant IL-2 polypeptides; 2) the instant claims specify cancer-associated antigens NY-ESO-1, Ras or WT-1, while the reference claims specify only the antigen WT-1; 3) while the instant claims are silent, the reference claims specify a first and a second disulfide bounds between Cys residues.
Regarding difference 1), one of skill in the art would have found it obvious to determine the copy number for a variant IL-2 gene to be incorporated in the polypeptide construct as claimed based on experimental needs (e.g., desired expression levels); regarding difference 2), Johannsen, Linard, and Terashima, cited in the 103 rejections above, teach cancer-associated antigen NY-ESO-1, Ras or WT-1; and regarding difference 3), Seidel, cited in the 103 rejections above, teaches various disulfide bounds formed between Cys residues that link the MHC I polypeptides, including those as specified in the reference claims (see throughout the specification of Seidel). One of skill in the art would have found it obvious to arrive at the instant claims from the reference claims in view of the teachings the cited prior art references, which remedy the differences between the two sets of claims.
Therefore, claims 22-39 are obvious over claims 1-4 of US patent 11878062.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/Primary Examiner, Art Unit 1671
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