DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim listing filed September 13, 2023 is pending.
Claims 1, 2, 5, and 6 are canceled.
Claims 3, 4, and 7-37 are pending.
Claims 1 and 7 are independent claims.
Election/Restriction
Applicant’s election without traverse to the invention of Invention I (claims 3, 4, and 8-37, in part, drawn to a method for treatment of a disease in an individual, classified in A61K 2039/585); and the species of:
selnoflast;
a cytokine release syndrome (CRS);
wherein administration of the NLRP3 inhibitor is associated with the first administration of the T cell engaging agent, wherein the NLRP3 inhibitor is administered intermittently, wherein the NLRP3 inhibitor is administered prior to the first administration of the T cell engaging agent, and wherein the NLRP3 inhibitor is administered orally;
a T cell bispecific antibody;
a T cell bispecific antibody comprising a third antigen binding moiety that binds to CD20 and an Fc domain composed of a first subunit and a second subunit;
a T cell bispecific antibody comprising:
a first antigen binding moiety that binds to CD3, comprising a heavy chain variable region sequence that is about 95% identical to the amino acid sequence of SEQ ID NO: 10 and a light chain variable region sequence that is about 95% identical to the amino acid sequence of SEQ ID NO: 11, and
a second antigen binding moiety and a third antigen binding moiety that bind to CD20,each comprising a heavy chain variable region sequence that is about 95% identical to the amino acid sequence of SEQ ID NO: 18 and a light chain variable region sequence that is about 95% identical to the amino acid sequence of SEQ ID NO: 19;
in the constant domain CL of each of the second and the third binding antigen moieties, the amino acid at position 124 is substituted independently by lysine (K) (numbering according to Kabat) and the amino acid at position 123 is substituted independently by arginine (R) (numbering according to Kabat) and in the constant domain CH1 the amino acid at position 147 is substituted independently by glutamic acid (E) (numbering according to Kabat EU index) and the amino acid at position 213 is substituted independently by glutamic acid (E) (numbering according to Kabat EU index);
an Fc domain comprising a modification promoting the association of the first and the second subunit of the Fc domain;
a non-Hodgkin lymphoma (NHL); and
an IL-6 cytokine
in the reply filed on February 2, 2026 is acknowledged.
Claims 7, 8, and 33-35 and claims 9-32, 36, and 37, in part, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 3 and 4 and claims 9-32, 36, and 37, in part, are currently under consideration.
Priority
The instant application claims foreign priority to EP22176323.8 filed 05/31/2022. A certified translated copy of EP22176323.8 has not been filed. Therefore, it is not clear if the foreign priority document has adequate support for the instant claims.
Claim Objections
Claims 23-27 and 36 are objected to because of the following informalities:
Claim 23 recites “wherein the T cell bispecific antibody comprises a third antigen binding moiety that binds to CD20 and/or an Fc domain composed of a first and a second subunit” where it should recite “wherein the T cell bispecific antibody further comprises a third antigen binding moiety that binds to CD20 and/or an Fc domain composed of a first and a second subunit” in lines 2 and 3.
Claim 24 recites “wherein the second and third antigen binding moiety are each a Fab molecule; (iii) an Fc domain composed of a first and a second subunit” where it should recite “wherein the second and third antigen binding moiety are each a Fab molecule; and (iii) an Fc domain composed of a first and a second subunit” in lines 16-18.
Appropriate correction is required.
Multiple Dependent Claims
Claims 12 and 19 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n).
Claim Rejections - 35 USC § 112
Improper Dependency
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 20 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Specifically, claim 20 recites “wherein the T cell bispecific antibody comprises an antigen binding moiety that binds to CD3 and an antigen binding moiety that binds to a target cell antigen” in lines 2 and 3. Claim 20 depends on claim 19 which recites “wherein the T cell bispecific antibody binds to CD3 and a target cell antigen” in lines 2 and 3.
The Applicant defines "bispecific" as an antibody is able to bind to at least two distinct antigenic determinants (e.g. see page 19, lines 21-25). Typically, a bispecific antibody comprises two antigen binding sites, each of which is specific for a different antigenic determinant (e.g. see page 19, lines 21-25). The Applicant defines "antigenic determinant" as synonymous with "antigen" and "epitope", and refers to a site (e.g. a contiguous stretch of amino acids or a conformational configuration made up of different regions of non-contiguous amino acids) on a polypeptide macromolecule to which an antigen binding moiety binds, forming an antigen binding moiety-antigen complex (e.g. see page 19, lines 26-29). The Applicant defines “antigen binding moiety” as a polypeptide molecule that binds, including specifically binds, to an antigenic determinant (e.g. see page 20, lines 3-14).
Thus, in view of the Applicant’s disclosure, a skilled artisan would readily recognize that that T cell bispecific antibody of claim 19 would inherently comprise antigen binding moieties for CD3 and the target cell antigen given that the only way for an antibody to bind its target antigen is through an antigen binding moiety.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Indefinite language
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 12-14, 16, and 31 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.
Claims 12 and 32 recite “wherein the inhibition is a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” in lines 2 and 3 and lines 1 and 2, respectively. It is unclear what the terms “clinically meaningful” and “statistically significant” in the claims mean or what the “clinically meaningful and/or statistically significant inhibition” are actually is. The terms “clinically meaningful” and “statistically significant” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore, the “inhibition” has been rendered indefinite.
Amending claims 12 and 32 to recite an specific degree of clinically meaningful and/or statistically significant inhibition would obviate this part of the rejection.
Claims 13 and 14 recite “the adverse effect” in line 2 and 3, respectively. Claims 13 and 14 depend on claim 3 which does not recite “an adverse effect.” Therefore, the term “the adverse effect” in claims 13 and 14 lacks antecedent basis and renders the claim indefinite.
Amending claim 3 to recite “an adverse effect” would obviate this part of the rejection.
Claim 13 also recites “wherein the adverse effect is one or more adverse effect” in lines 2 and 3. The recitation of “the adverse effect” in claim 13 means that there is only one adverse effect. However, the recitation of “one or more adverse effect” also in claim 13 means that there can be more than one adverse effect. The recitation of a singular adverse effect followed by plural adverse effects renders the claim indefinite because it is unclear how many adverse effects are being monitored in the claimed method.
Amending claim 13 to delete “one or more adverse effect” would obviate this part of the rejection.
Claim 16 recites “the first administration” in line 3 and 5 and line 6, respectively. Claim 16 depends on claim 3 which does not recite “a first administration.” Therefore, the term “the first administration” in claim 16 lacks antecedent basis and renders the claim indefinite.
Amending claim 3 to recite “a first administration” would obviate this part of the rejection.
Claim 31 recites “wherein the cancer is Non-Hodgkin lymphoma (NHL)” in line 2. Claim 31 depends on claim 30 which recites “wherein the cancer is (i) a CD20-expressing cancer or (ii) a B-cell cancer” in lines 2 and 3. Given that there are three cancers recites in claim 30, it is unclear which cancer in claim 30 that claim 31 is referring to. Therefore, the term “the cancer” in claim 31 lacks antecedent basis and renders the claim indefinite.
Furthermore, if “the cancer” in claim 31 is referring to the first cancer recited in claim 30, then there is a potential issue under 35 U.S.C. 112(d) for not further limiting the scope of claim 30 because not all Non-Hodgkin lymphomas express CD20 or are B-cell cancers.
Amending claim 31 to recite “wherein the CD20-expressing cancer or B-cell cancer is Non-Hodgkin lymphoma (NHL)” would obviate this part of the rejection and eliminate any potential rejections under 35 U.S.C. 112(d).
Written Description
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 3, 4, 9-32, 36, and 37 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 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.
The instant claims are drawn to a method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and(b) the administration of an NLRP3 inhibitor to the individual.
The Applicant has disclosed two working examples, both of which only apply MCC950 (also known as CP-456,773) as the NLRP3 inhibitor and an anti-CD3/CD20 T cell bispecific antibody (TCB) comprising a first and a second antigen binding domain, wherein the first antigen binding domain binds CD3 and comprises HCDRs1-3 as SEQ ID NOs: 4-6, respectively, and LCDRs1-3 as SEQ ID NOs: 7-9, respectively, and wherein the second antigen binding domain binds CD20 and comprises HCDRs1-3 as SEQ ID NOs: 12-14, respectively, and LCDRs1-3 as SEQ ID NOs: 15-17, respectively, as the T cell engaging agent (e.g. see Table spanning pages 43-45; and Examples 1 and 2 spanning pages 47-49).
Further regarding the claimed genus of T cell engaging agents, Applicant has defined a "T cell engaging agent" as an immunotherapeutic agent that exerts its effect through the activity of T cells, particularly cytotoxic T cells (e.g. see page 18, lines 15-27). Such activity of T cells may include cellular response(s) of T cells, particularly CD4+ and/orCD8+ T cells, such as proliferation, differentiation, expression of activation markers, cytokine secretion, cytotoxic effector molecule release and/or cytotoxic activity. T cell engaging agents as contemplated herein typically comprise an antigen binding moiety that enables their binding to a target cell antigen on a target cell such as a tumor cell. Such T cell engaging agents exert effects on their target cell, such as lysis of the target cell, through the activity of T cells. Exemplary T cell engaging agents include T cell bispecific antibodies (TCBs), chimeric antigen receptor (CAR) expressing T cells (CAR-T cells), and T cell receptor (TCR)-based approaches such as ImmTACs ("Immune mobilising monoclonal T-cell receptors Against Cancer"; bispecific fusion proteins of an engineered TCR and an antibody fragment, capable of binding to a T cell and a target cell) or TCR-modified T cells featuring engineered T cell receptors capable of binding to a specific antigenic determinant on a target cell (TCR-T cells) (e.g. see page 18, lines 15-27).
The Applicant has also disclosed the following four TCBs in addition to the anti-CD3/CD20 TCB disclosed in Example 1 and 2: CEA-TCB (cibisatamab; Bacac et al. (2016) Clin Cancer Res 22, 3286-97), CD20-TCB (glofitamab; Bacac et al. (2018) Clin Cancer Res 24, 4785-97), WT1-TCB (Augsberger et al. (2021) Blood 138, 2655-69) and BCMA-TCB (Seckinger et al. (2017) Cancer Cell 31, 396-410) (e.g. see page 2, lines 1-5).
It is noted that the Applicant has disclosed that glofitamab is also known as CD20-TCB which comprises SEQ ID NOs: 4-23 (e.g. see page 2, lines 1-6; and page 47, lines 10-15).
Regarding the claimed NLRP3 (also known as NACHT, LRR and PYD domains-containing protein 3; NOD-,LRR- and pyrin domain-containing protein 3; NLR (NOD-like receptor) family pyrin domain containing 3; NOD-like receptor protein 3; or cryopyrin) inhibitor, the Applicant has disclosed that NLRP3 inhibitors are compounds, in particular small molecule pharmacological inhibitors, that inhibit the NLRP3 inflammasome (e.g. see page 4, lines 24-27). For example, NLRP3 inhibitors may disrupt NLRP3-NLRP3 interactions or NLRP3-ASC interactions, or may be directed at the ATP-binding domain of NLRP3 resulting in blockade of its ATPase activity (e.g. see page 4, lines 24-27).
Exemplary NLRP3 inhibitors disclosed by the Applicant in addition to MCC950 include selnoflast, emlenoflast, CY-09, IZD334 (also known as Somalix; Inflazome), IZD174 (also known as Inzomelid; Inflazome), DFV890 (also known as IFM-2427), IFM-632, IFM-514, JT194, JT349, NT-0167, NT-0796, NT-0249, VENT-01, VTX3232, VTX2735, BT032, BT132, OLT1177, ADS-032, ZYIL1, HY209, AC-201, AC-203, and tranilast (also known as Rizaben) (e.g. see page 5, line 1 – page 7, line 6).
When given the broadest reasonable interpretation in light of specification, the T cell engaging agent and the NLRP3 inhibitor of the instant invention are defined broadly to be any agent that engages a T cell and any agent that inhibits NLRP3, respectively.
It is noted that the broadest claim (claim 3) does not indicate sufficient structure for the genera of T cell engaging agents and the NLRP3 inhibitors.
Only dependent claims 8 and 9 recite sufficient structure for the genus of NLRP3 inhibitors but not for the genus of T cell engaging agents.
Dependent claims 18-28 and 36 limit the structure of the T cell engaging agent to a T cell bispecific antibody. Dependent claims 19-28 and 36 limit the T cell bispecific antibody to one that binds CD3 and a target cell antigen. Dependent claims 21-28 and 36 limit the target cell antigen to CD20. Only Dependent claims 22, 24-28, and 36 recite sufficient structure for the genus of T cell engaging agents but not for the genus of NLRP3 inhibitors.
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 (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3). 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.”
Regarding the subgenus of T cell engagers which are drawn to CAR-T cells, it is well known that antigen binding domains of CARs fall in three general categories, either single chain variable fragments (scFvs) derived from antibodies, Fab’s selected from libraries, or natural ligands that engage their cognate receptor (e.g. see Sadelain et al. Cancer Discov. 2013;3(4):388–398, page 389, left column, second paragraph under “CAR TARGETING”). Successful examples in each of these categories have been reported. scFvs derived from murine immunoglobulins are commonly used, as they are easily derived from well-characterized monoclonal antibodies. They, however, may prove to be more immunogenic than Fab’s derived from human libraries or invariant human ligands (e.g. see Sadelain et al. Cancer Discov. 2013;3(4):388–398, page 389, left column, second paragraph under “CAR TARGETING”).
Regarding the subgenus of T cell engagers which are drawn to TCR-based formats, in both antibodies and TCRs, sequence and structural diversity is concentrated in six hypervariable loops, known as the complementarity determining regions (CDRs) (e.g. see Wong et al. Front. Immunol. 2019, 10: 2454, 1-11, paragraph spanning pages 1 and 2). There are three in the TCRα chain (CDRα1–CDRα3) and three in the TCRβ chain (CDRβ1–CDRβ3). Likewise, the light chain and heavy chain of antibodies have three CDRs each (CDRL1–CDRL3, CDRH1–CDRH3). In TCRs, CDR1, and CDR2 typically contact the MHC's conserved α-helices while the CDR3 almost always contacts the peptide antigen. The structural complementarity between the binding sites of the antigen receptor and their cognate antigen governs the binding interactions. As the CDRs form the majority of the binding site, their conformations are critical to the binding (e.g. see Wong et al. Front. Immunol. 2019, 10: 2454, 1-11, paragraph spanning pages 1 and 2).
Regarding the subgenera of T cell engagers which are drawn to TCBs (including CD3-binding and CD2/CD20-binding TCBs), CARs, and TCR-based formats, given that CARs generally comprise antibody-derived antigen binding domains and the similarities between the CDRs of TCRs and antibodies, the following argument still applies to the instant invention. Artisans are well aware that knowledge of a given antigen (for instance a T cell antigen, such as CD3, or a target cell antigen, such as CD20) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. (J. Mol. Biol., 2003, 334:103-118) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document).
As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen, as there does not appear to be any common or core structure present within all antibodies that gives rise to the function of antigen binding. Further, given data, such as that of Edwards et al., indicating the diversity of sequences in a population of antibodies that bind to a given antigen, no number of species appears to reasonably representative of the breadth of the genus of antibodies that bind the given antigen.
It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antigen binding molecule to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway Jr et al., Immunology, 3rd Edition, 1997 Garland Publishing Inc., pages 3:1-3:11.see entire selection).
Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
This applies to the instant invention which is drawn to a genus of T cell engagers which encompass the subgenera which are drawn to TCBs (including CD3-binding and CD2/CD20-binding TCBs), CARs, and TCR-based formats.
It is noted that the genus of T cell engagers as currently claimed are not limited TCBs, CARs, and TCR-based formats, but also encompasses other types of T cell engagers including small molecules, peptides, etc. Nonetheless, the same logic applies. Small molecule or peptide-based T cell engagers still require very precise structure in order confer binding function.
Regarding the claimed genus of NLRP3 inhibitors, although the claimed NLRP3 inhibitors are not limited to antibodies, CARs, or TCRs, the same logic outlined above still applies. The genus of NLRP3 inhibitors encompass not only the small molecules disclosed in the specification and the claims but also encompass polypeptide-based (such as antibodies, CARs, or TCRs) NLRP3 inhibitors. These NLRP3 inhibitors still require very precise structure in order confer binding function.
As noted above, the Applicant has disclosed several species T cell engagers, all of which are TCBs (cibisatamab (CEA-TCB), glofitamab (CD20-TCB), WT1-TCB, and BCMA-TCB) and many species NLRP3 inhibitors, all of which are small organic molecules (MCC950, selnoflast, emlenoflast, CY-09, IZD334 (also known as Somalix; Inflazome), IZD174 (also known as Inzomelid; Inflazome), DFV890 (also known as IFM-2427), IFM-632, IFM-514, JT194, JT349, NT-0167, NT-0796, NT-0249, VENT-01, VTX3232, VTX2735, BT032, BT132, OLT1177, ADS-032, ZYIL1, HY209, AC-201, AC-203, and tranilast (also known as Rizaben)).
Such a disclosure does not serve to provide sufficient written description of the claimed genera of T cell engagers and NLRP3 inhibitors. The disclosure does not identify sufficient structural features or combination of features which give rise to the function of T cell engagement or NLRP3 inhibition, respectively. Additionally, there does not appear to be any reasonable shared structure present in the genera of recited T cell engagers and NLRP3 inhibitors which gives rise to their functional activity. Ultimately, identifying a T cell engager or an NLRP3 inhibitor simply on the basis of engaging a T cell or inhibiting NLRP3, respectively, rather than by identifying the sequence/structure, namely the CDRs, amino acid sequence, small molecule structure, etc., of the T cell engagers or an NLRP3 inhibitors in question is generally insufficient to provide written description.
The claims are drawn to broad genera of T cell engagers and NLRP3 inhibitors which are functionally defined by their ability to engage a T cell and inhibit NLRP3, respectively, without reciting a corresponding structure expected to correlate with this ability as supported by Applicant’s disclosure. Thus, there is insufficient written description for the breadth of T cell engagers and NLRP3 inhibitors as currently claimed, which are distinct and diverse and do not share a common structure that contributes to a common ability to engage a T cell and inhibit NLRP3, respectively.
Therefore, in view of the breadth of the claims and the limited disclosure, artisans would reasonably conclude that applicant was not in possession of the full breadth of T cell engagers and NLRP3 inhibitors as encompassed by the claims at the time the instant application was filed.
Amending the claim 3 to limit the T cell engager to cibisatamab, glofitamab, WT1-TCB, or BCMA-TCB, or a TCB comprising their CDR amino acid sequences (while also reciting their respective target cell antigen); and to limit the NLRP3 inhibitor to MCC950, selnoflast, emlenoflast, CY-09, IZD334, IZD174, DFV890, IFM-632, IFM-514, JT194, JT349, NT-0167, NT-0796, NT-0249, VENT-01, VTX3232, VTX2735, BT032, BT132, OLT1177, ADS-032, ZYIL1, HY209, AC-201, AC-203, or tranilast would obviate this part of the rejection.
Enablement
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 3, 4, 9-32, 36, and 37 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 method for treatment of diffused large B cell lymphoma (DLBCL) in an individual, wherein said method comprises (a) the administration of an glofitamab to the individual, and (b) the administration of MCC950 to the individual; does not reasonably provide enablement for a method for treatment of any disease in an individual, wherein said method comprises (a) the administration of any T cell engaging agent to the individual, and (b) the administration of any NLRP3 inhibitor to the individual.
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/or use the invention commensurate in scope with these claims.
The factors considered in determining whether a disclosure would require undue experimentation include:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP § 2164.01.
Nature of the invention/Breadth of the claims
Independent claim 3 is drawn to method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and(b) the administration of an NLRP3 inhibitor to the individual.
Dependent claim 4 limits the method to that wherein the administration of the NLRP3 inhibitor prevents or mitigates an adverse effect related to the administration of the T cell engaging agent.
Dependent claims 10 and 12 limit the method to that wherein the administration of the NLRP3 inhibitor inhibits an adverse effect related to the administration of the T cell engaging agent. Dependent claim 12 limits the inhibition to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition.
Dependent claim 11 limits the method to that wherein the administration of the NLRP3 inhibitor does not inhibit a desired effect related to the administration of the T cell engaging agent.
Dependent claim 9 limits the NLRP3 inhibitor to selnoflast.
Dependent claims 18-28 and 36 limit the structure of the T cell engaging agent to a T cell bispecific antibody (TCB).
Dependent claims 19-28 and 36 limit the TCB to one that binds CD3 and a target cell antigen. Dependent claims 21-28 and 36 limit the target cell antigen to CD20.
Dependent claims 22, 24-28, and 36 limit the anti-CD20/CD3 TCB to that which comprising a first and a second antigen binding domain, wherein the first antigen binding domain binds CD3 and comprises HCDRs1-3 as SEQ ID NOs: 4-6, respectively, and LCDRs1-3 as SEQ ID NOs: 7-9, respectively, and wherein the second antigen binding domain binds CD20 and comprises HCDRs1-3 as SEQ ID NOs: 12-14, respectively, and LCDRs1-3 as SEQ ID NOs: 15-17, respectively.
Dependent claims 23-28 and 36 limit the anti-CD20/CD3 TCB to a trivalent TCB comprising a second anti-CD20 antigen binding domain.
Dependent claims 24-28 and 36 limit the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains, to that wherein the second anti-CD20 antigen binding domain comprises HCDRs1-3 as SEQ ID NOs: 12-14, respectively, and LCDRs1-3 as SEQ ID NOs: 15-17, respectively.
Dependent claim 25 the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains of claim 24, to that wherein the first antigen binding domain binds that CD3 comprises a VH amino acid sequence of SEQ ID NOs:10 and VL amino acid sequence of SEQ ID NOs: 11, and the second and third antigen binding domains which bind CD20 both comprise VH amino acid sequence of SEQ ID NOs: 18 and VL amino acid sequence of SEQ ID NOs: 19.
Dependent claim 28 the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains of claim 24 to glofitamab.
Dependent claims 29-31 and 37 limit the disease to cancer.
Dependent claims 30 and 31 limit the cancer to (i) a CD20-expressing cancer or (ii) a B-cell cancer.
Dependent claim 31 limits the cancer to Non-Hodgkin lymphoma (NHL).
Dependent claim 37 limits the cancer to a cancer expressing the target cell antigen of the T cell engaging agent.
State of the prior art/Predictability of the art
Regarding the use of any T cell engager for treating any disease, Xue et al. 2026 (Oncoimmunol. 15(1), 2632421; 1-16) teach that T cell engagers (TCEs) represent the most clinically advanced subclass of immune cell engagers, distinguished by their ability to establish MHC-independent interactions between T cells and tumor cells through parallel recognition of tumor-associated antigens and T cell surface receptors (e.g. see paragraph spanning pages 1 and 2). This interplay promotes the formation of functional immunological synapses and triggers cytotoxic effector programs within engaged T cells. By directly coupling the T cell receptor complex to tumor antigens, TCEs can circumvent tumor immune evasion driven by MHC downregulation and entirely bypass the requirement for conventional antigen presentation-dependent immune responses (e.g. see paragraph spanning pages 1 and 2).
Xue et al. also teach that while substantial clinical success has been achieved in hematologic malignancies, major challenges, such as limited activity in solid tumors, continue to constrain broader application (e.g. see Abstract). Xue et al. also teach that solid tumors pose major challenges for bispecific antibody therapies due to physical and metabolic barriers within the tumor microenvironment that limit penetration, stability, and immune activity (e.g. see paragraph spanning pages 7 and 8). Dense extracellular matrix, elevated interstitial pressure, and abnormal vasculature restrict antibody distribution and create heterogeneous drug exposure, often necessitating higher systemic dosing that still fails to achieve uniform intratumoral concentrations. Concurrently, immunosuppressive and destabilizing conditions, including hypoxia, acidosis, high lactate and adenosine levels, nutrient deprivation, and elevated extracellular ATP, impair T cell function and accelerate antibody degradation, further compromising efficacy (e.g. see paragraph spanning pages 7 and 8).
Xue et al. further teach that the studies summarized in Table 2 highlight both the breadth and the current limitations of canonical CD3-based T cell engager development (e.g. see paragraph spanning pages 6 and 7). While antigen diversity, molecular engineering, and conditional activation strategies continue to expand the therapeutic scope of this modality, durable late-stage success remains confined to a small number of highly optimized programs, underscoring the importance of target selection, format choice, and safety engineering for successful clinical translation (e.g. see paragraph spanning pages 6 and 7).
Ultimately, Xue et al. teach that there are a number of factors, including the importance of target selection, format choice, and safety engineering for successful clinical translation, need to be considered in the design and application of T cell engagers. These teachings highlight the unpredictability of applying any T cell engager for the treatment of any disease. It is unpredictable to treat any disease with any T cell engager with no particular disease and/or target in mind. In fact, given that durable late-stage success remains confined to a small number of highly optimized programs, Xue et al.’s teachings still underscore the unpredictability of the art even with a particular disease and/or target in mind.
Regarding the use of any NLRP3 inhibitor in combination with any T cell engager for the treatment of any disease, Namme et al. 2026 (Expert Opin. Ther. Pat. 36(5), 471-484) teach that therapeutic indications of NLRP3 inhibitors have been suggested for a wide range of diseases (e.g. see page 480, left column, third paragraph). There is increasing emphasis on non-covalent NLRP3 inhibitors, particularly MCC950 analogs and NACHT-binding chemotypes, alongside a growing focus on safety and regulatory considerations (e.g. see page 480, paragraph spanning left and right columns).
Although significant advances have been achieved in the preclinical development of NLRP3 inhibitors, challenges remain in translating these advances into clinical practice (e.g. see page 480, right column, second paragraph). One of the issues is not only the target validation but also identifying appropriate patient populations and determining the optimal timing of intervention. In many diseases inflammasome activation appears multifactorial and temporally dependent and validated biomarkers for NLRP3 suppression are still lacking, and consequently clinical implementation remains challenging. Another obstacle in developing NLRP3 inhibitors for clinical use is distinguishing the pathological suppression of the NLRP3 inflammasome from its physiological functions in the innate immune system. Although a high degree of specificity has been achieved by current NLRP3 inhibitors, the clinical benefit of using highly potent inhibitors has yet to be validated (e.g. see page 480, right column, second paragraph).
Ultimately, Namme et al. teach that there are many factors that influence the therapeutic success of NLRP3 inhibitors including target validation, patient population selection, and optimal timing of intervention. These teachings, therefore, highlight the unpredictability of applying any NLRP3 inhibitor in combination with any T cell engager for the treatment of any disease.
The art teachings outlined above applies to the instant case where the claims are drawn to a method for treatment of any disease in an individual, wherein said method comprises (a) the administration of any T cell engaging agent to the individual, and (b) the administration of any NLRP3 inhibitor to the individual.
Regarding the limitations in claims 4 and 10-12 which are drawn to the NLRP3 inhibitor influencing an adverse (claims 4, 10, and 12) or desired (claim 11) effect related to the administration of the T cell engaging agent, Géraud et al. 2024 (Eur. J. Cancer. 205(114075), 1-19) teach that the anticipated widespread use of T cell engagers poses implementation challenges and highlights the need for guidance to anticipate, mitigate, and manage adverse events (e.g. see Abstract). The most common adverse reaction to T cell engager therapy is cytokine release syndrome (CRS) but other adverse events include immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), infections, tumor flare reaction and cytopenias (e.g. see Abstract).
Géraud et al. also teach that the desired effects of a T cell engager include an immediate anti-tumor immune response, T-cell proliferation, and tumor cell lysis (e.g. see page 1, right column, first paragraph; and page 2, left column, second paragraph).
Ultimately, Géraud et al. teach that there are several adverse and desired effects related to the administration of a T cell engaging agent. This applies to the instant case where claims 4 and 10-12 are drawn to the NLRP3 inhibitor influencing an adverse (claims 4, 10, and 12) or desired (claim 11) effect related to the administration of the T cell engaging agent.
Working examples/Guidance in the specification
The Applicant has disclosed one working example for a method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and (b) the administration of an NLRP3 inhibitor to the individual (e.g. see Example 2, spanning pages 48 and 49). Specifically, the Applicant discloses a method for treatment of diffused large B cell lymphoma (DLBCL) (disease) with glofitamab (anti-CD20/CD3 TCB) and MCC950 (NLRP3 inhibitor) (e.g. see page 48, lines 6-14). The combination of glofitamab and MCC950 for treating DLBCL retained the anti-tumor activity of the TCB while also while reducing the levels of IL-1β and IL-6 (e.g. see page 49, lines 1-4). This resulted in preventing body weight loss induced by the first treatment
with glofitamab. Altogether, this data support the use of an NLRP3 inhibitor for the mitigation of CRS symptoms that may be induced by treatment with glofitamab for DLBCL, specifically (e.g. see page 49, lines 1-4).
The Applicant also discloses that the disease is cancer and lists numerous exemplary cancers (e.g. see page 38, line 10; and page 38, lines 18-30). The Applicant also discloses that the cancer is a cancer expressing the target cell antigen of the T cell engaging agent (e.g. see page 39, lines 1 and 2). The Applicant also discloses that the cancer is a CD20-expressing cancer (e.g. see page 39, lines 3-11). The Applicant also discloses that the cancer is a B-cell cancer, particularly a CD20-positive B-cell cancer, and lists many further cancers (e.g. see page 39, lines 12-30). The Applicant also discloses that the cancer is treatable by the T cell engaging agent (e.g. see page 39, lines 31 and 32).
Amount of experimentation necessary
The Applicant has only disclosed a method for treatment of diffused large B cell lymphoma (DLBCL) with glofitamab and MCC950, yet, the claims are not limited to a method of treating DLBCL with glofitamab and MCC950. The claimed method encompasses a method for treatment of any disease with any T cell engager and any NLRP3 inhibitor. There is insufficient objective evidence that the disclosed method for treatment of diffused large B cell lymphoma (DLBCL) with glofitamab and MCC950 can be extrapolated to provide guidance and direction for the claimed method for treatment of any disease with any T cell engager and any NLRP3 inhibitor.
The art underscores the importance of target selection, format choice, and safety engineering for successful clinical translation in the design of T cell engagers and highlights the limited durable late-stage success of a small number of highly optimized programs (Xue et al.). These teachings not only emphasize the unpredictability of applying any T cell engager for the treatment of any disease, but also demonstrate that even with a particular disease and/or target in mind there is uncertainty regarding the success of treating said disease.
Furthermore, the art also teaches that there are many factors that influence the therapeutic success of NLRP3 inhibitors including target validation, patient population selection, and optimal timing of intervention, highlighting the unpredictability of applying any NLRP3 inhibitor in combination with any T cell engager for the treatment of any disease (Namme et al.).
Thus, based on the content of the disclosure in view of the prior art teachings regarding the unpredictability of treating any disease with any T cell engager in combination with any NLRP3 inhibitor with no particular disease and/or target in mind, or even with a particular disease and/or target in mind, a skilled artisan, through extensive trial-and-error experimentation, would have to identify a specific disease and its suitable T cell engager target and a suitable NLRP3 inhibitor to be used in combination with a reasonable expectation of success. This quantity of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the method for the breadth of what is claimed.
Regarding the limitation in claim 4 which is drawn to the administration of the NLRP3 inhibitor preventing or mitigating an adverse effect related to the administration of the T cell engaging agent, the burden of enabling the prevention of an adverse effect related to the administration of the T cell engaging agent (i.e. the need for additional testing) would be greater than that of enabling a mitigation or inhibition due to the need to screen those subjects susceptible to such adverse effects related to the administration of the T cell engaging agent and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to an adverse effect related to the administration of the T cell engaging agent within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed NLRP3 inhibitor in preventing an adverse effect related to the administration of the T cell engaging agent.
While the specification discloses an example of treating DLBCL with glofitamab (T cell engager) and MCC950 (NLRP3 inhibitor) and demonstrates that the use of MCC950 mitigates CRS symptoms that may be induced by treatment for DLBCL with glofitamab, the treatment does not teach prevention of CRS symptoms. Therefore, the specification at most discloses mitigating or inhibiting an adverse effect related to the administration of the T cell engaging agent, but not prevention.
Regarding the limitations in claims 4 and 10-12 which are drawn to the NLRP3 inhibitor influencing an adverse (claims 4, 10, and 12) or desired (claim 11) effect related to the administration of the T cell engaging agent, the Applicant has only disclosed an example of treating DLBCL with glofitamab (T cell engager) and MCC950 (NLRP3 inhibitor) and demonstrates that the use of MCC950 mitigates CRS symptoms and does not affect T cell cytotoxicity or activation. However, the claimed method encompasses the NLRP3 inhibitor having an effect on any adverse or desired effect related to the administration of the T cell engaging agent. There is insufficient objective evidence that the Applicant’s disclosure of the NLRP3 inhibitor mitigating CRS symptoms and retention of T cell cytotoxicity or activation can be extrapolated to provide guidance and direction for the claimed NLRP3 inhibitor influencing any adverse or desired effect related to the administration of the T cell engaging agent.
Thus, based on the content of the disclosure in view of the prior art teachings regarding T cell engagers having several adverse and desired effects, a skilled artisan, through extensive trial-and-error experimentation, would have to identify specific adverse and desired effects related to the administration of the T cell engaging agent and demonstrate that they are influenced by the administration of an NLRP3 inhibitor with a reasonable expectation of success. This quantity of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the method for the breadth of what is claimed.
Thus, the specification does not enable one of ordinary skill in the art to use what is claimed and therefore claims 3, 4, and 9-37 are rejected under 35 U.S.C. 112(a).
Amending claim 3 to limit the disease to diffused large B cell lymphoma (DLBCL), the T cell engager to glofitamab, and the NLRP3 inhibitor to MCC950; amending claim 4 to delete the phrase “prevents or”; amending claims 4, 10, and 12 to limit the adverse effect to CRS; and amending claim 11 to limit this desired effect to T cell cytotoxicity and/or T cell activation would obviate this part of the rejection.
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, 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.
Claims 3, 4, 10-20, 29-32, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) in view of Zhang 2021 (WO2021011592).
Independent claim 3 is drawn to method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and(b) the administration of an NLRP3 inhibitor to the individual.
Dependent claim 4 limits the method to that wherein the administration of the NLRP3 inhibitor prevents or mitigates an adverse effect related to the administration of the T cell engaging agent.
Dependent claims 10 and 12 limit the method to that wherein the administration of the NLRP3 inhibitor inhibits an adverse effect related to the administration of the T cell engaging agent. Dependent claim 12 limits the inhibition to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition.
Dependent claim 11 limits the method to that wherein the administration of the NLRP3 inhibitor does not inhibit a desired effect related to the administration of the T cell engaging agent.
Dependent claim 13 limits the adverse effect to CRS.
Dependent claim 14 limits the method to that wherein the administration of the NLRP3 inhibitor is upon manifestation of the adverse effect in the individual.
Dependent claim 15 limits the method to that wherein the administration of the NLRP3 inhibitor is before administration of the T cell engaging agent, intermittent, and orally.
Dependent claim 16 limits the method to that wherein the administration of the NLRP3 inhibitor is associated with the first administration of the T cell engaging agent, wherein the administration of the NLRP3 inhibitor is prior to the first administration of the T cell engaging agent.
Dependent claim 17 limits the method to that wherein the administration of the T cell engaging agent is the first administration of the T cell engaging agent to the individual.
Dependent claims 18 limits the structure of the T cell engaging agent to a T cell bispecific antibody (TCB).
Dependent claims 19 and 20 limit the TCB to one that binds CD3 and a target cell antigen.
Dependent claims 29-31 and 37 limit the disease to cancer.
Dependent claims 30 and 31 limit the cancer to (i) a CD20-expressing cancer or (ii) a B-cell cancer.
Dependent claim 31 limits the cancer to Non-Hodgkin lymphoma (NHL).
Claim 32 limits the inhibition of claim 11 to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition.
Dependent claim 37 limits the cancer to a cancer expressing the target cell antigen of the T cell engaging agent.
Regarding claims 3, 4, 10, 12, 13, 29, and 37, Khadka et al. teach treating hematological malignancies (cancers) with bi-specific T cell engagers (BiTEs) (e.g. see page 851, first paragraph). Khadka et al. also teach that although a significant portion of the innovation and engineering has been invested toward improving the efficacy and potency of T cell-engaging immunotherapies, these therapeutic strategies are prone to varying degrees of toxicities (or adverse effects), including cytokine release syndrome (CRS). Khadka et al. also teach that for ensuring success of these promising and revolutionary therapies, both systematic grading and therapeutic management of CRS are essential for the field of immuno-oncology (e.g. see page 851, first paragraph).
Regarding claim 18, Khadka et al. also teach that BiTEs are T cell bispecific antibodies comprising two single chain variable fragments (scFvs) connected with a flexible short amino acid linker that targets distinct antigens on T cell and tumor cells in tandem (e.g. see page 853, fourth paragraph).
Regarding claim 19, Khadka et al. also teach BiTEs that target CD3 and a target cell antigen (e.g. see page 853, fourth paragraph).
Regarding claim 30, Khadka et al. also teach that BiTE has shown promising efficacy against relapsed or refractory B-cell acute lymphoblastic leukemia (e.g. see page 853, fourth paragraph).
Regarding claim 31, Khadka et al. also teach treating non-Hodgkin lymphoma with blinatumomab, a CD19/CD3 bispecific BiTE (e.g. see page 853, fourth paragraph).
Khadka et al. do not explicitly teach a method for treating by administering a T cell engaging agent or that the method comprises administering an NLRP3 inhibitor in combination with the T cell engaging agent.
Zhang teaches a method of inhibiting, preventing or treating NRLP3 inflammasome-associated disease in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of an NLRP3 inhibitor (e.g. see claims 6 and 7). It is noted that formulas I (claim 6) and II (claim 7) are, or are at least scaffolds for, NLRP3 inhibitors (e.g. see page 3, lines 14-28; and page 4, lines 8-10).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Khadka et al. to incorporate the teachings of Zhang to include explicitly teach a method for treating by administering a T cell engaging agent and that the method comprises administering an NLRP3 inhibitor in combination with the T cell engaging agent. This is because in order to ensure the success of T cell-engaging immunotherapies therapeutic management of CRS is essential (Khadka et al.).
Given that T cell-engaging immunotherapies are prone to varying degrees of toxicities including CRS which limit their therapeutic efficacy (Khadka et al.), strategies to ensure the success of T cell-engaging immunotherapies include therapeutic management of CRS (Khadka et al.), and NLRP3 inhibitors are used to treat NRLP3 inflammasome-associated diseases such as CRS (Zhang); it would have been obvious to a skilled artisan to modify the treatment of hematological malignancies with a T cell engager as taught by Khadka et al. to further include an NLRP3 inhibitor to be used in combination with the T cell engager with a reasonable expectation of success. A skilled artisan would have reasonably anticipated that in developing a method for treating a disease with a T cell engager, the efficacy of said treatment would be limited by CRS. Therefore, it would have been obvious to a skilled artisan to mitigate said CRS in said method by administering an NLRP3 inhibitor, which is known to treat T cell engager-induced CRS, in combination with the T cell engager with a reasonable expectation of success.
Regarding the limitations “wherein the administration of the NLRP3 inhibitor prevents or mitigates an adverse effect related to the administration of the T cell engaging agent” (claim 4), “wherein the administration of the NLRP3 inhibitor inhibits an adverse effect related to the administration of the T cell engaging agent” (claim 10) “wherein the inhibition to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 12), and “wherein the administration of the NLRP3 inhibitor does not inhibit a desired effect related to the administration of the T cell engaging agent” (claim 11) “wherein the inhibition is a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 32); Khadka et al. and Zhang are silent on these properties.
However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are 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).
Although Khadka et al. and Zhang are silent with regard to the NLRP3 inhibitor having the properties recited in claims 4, 10-12, and 32, it is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the NLRP3 inhibitor taught by Khadka et al. in view of Zhang would have the claimed properties recited in claims 4, 10-12, and 32.
When a claim recites using an old composition or structure (e.g., an NLRP3 inhibitor) and the use is directed to a result or property of that composition or structure (properties recited in claims 4, 10-12, and 32) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The properties recited in claims 4, 10-12, and 32 flow naturally from the teachings of the prior art. (citing Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)).
An obvious formulation cannot become nonobvious simply by measuring and claiming an activity of the formulation in a particular context, “because ‘[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property.’” Persion Pharm., slip op. at 13 (Fed. Cir. Dec. 27, 2019) (citing Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012)); see also Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 249 (1945) (“It is not invention to perceive that the product which others had discovered had qualities they failed to detect.”).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Regarding the administration steps “wherein the administration of the NLRP3 inhibitor is upon manifestation of the adverse effect in the individual” (claim 14), “wherein the administration of the NLRP3 inhibitor is before administration of the T cell engaging agent, intermittent, and orally” (claim 15), “wherein the administration of the NLRP3 inhibitor is associated with the first administration of the T cell engaging agent, wherein the administration of the NLRP3 inhibitor is prior to the first administration of the T cell engaging agent” (claim 16), and “wherein the administration of the T cell engaging agent is the first administration of the T cell engaging agent to the individual” (claim 17); Khadka et al. and Zhang are silent on these administration steps.
However, determination of the optimal intervals of treatment and the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. The duration of treatment, the effective dosages, and like factors are well within the knowledge and expertise of the medical practitioner.
It would have been obvious to one of ordinary skill in the art at the time Applicants' invention was filed to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Further, if there are any differences between Applicant’s claimed method and that suggested by the teachings of the prior art, the differences would appear to be minor in nature. Although the prior art do not teach all the various permutations of interval ranges as recited in claims 14-17, it would be conventional and within the skill of the art to identify the optimal administration steps. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). See MPEP §§ 2144.05 part II A.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) in view of Zhang 2021 (WO2021011592), as applied to claim 3, and further in view of Schwaid and Spencer 2020 (J. Med. Chem. 64(1), 101-122).
Dependent claim 9 limits the NLRP3 inhibitor to selnoflast.
The combined teachings of Khadka et al. in view of Zhang pertaining to claim 3, and the rationale for combining them are outlined in the 103 rejection above.
The combined reference teachings do not teach that the NLRP3 inhibitor is specifically selnoflast.
Schwaid and Spencer teach that somalix, also known as selnoflast, is a peripherally restricted NLRP3 inhibitor.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of Khadka et al. in view of Zhang as applied to claim 3, and incorporate the teachings of Schwaid and Spencer to include that the NLRP3 inhibitor is specifically selnoflast.
Given that somalix, also known as selnoflast, is a known peripherally restricted NLRP3 inhibitor; it would have been obvious to a skilled artisan to specifically apply selnoflast as the NLRP3 inhibitor in the method of treating a disease with a combination of a T cell engager and an NLRP3 inhibitor as taught by Khadka et al. in view of Zhang with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 21-28 and 36 is rejected under 35 U.S.C. 103 as being unpatentable over Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) in view of Zhang 2021 (WO2021011592), as applied to claims 3 and 18-20, and further in view of Hutchings et al. 2021 (J Clin Oncol 39, 1959-1970) as evidenced by Strohl 2024 (Antib Ther. 7(2):132–156).
Dependent claims 21-28 and 36 limit the target cell antigen to CD20.
Dependent claims 22, 24-28, and 36 limit the anti-CD20/CD3 TCB to that which comprising a first and a second antigen binding domain, wherein the first antigen binding domain binds CD3 and comprises HCDRs1-3 as SEQ ID NOs: 4-6, respectively, and LCDRs1-3 as SEQ ID NOs: 7-9, respectively, and wherein the second antigen binding domain binds CD20 and comprises HCDRs1-3 as SEQ ID NOs: 12-14, respectively, and LCDRs1-3 as SEQ ID NOs: 15-17, respectively.
Dependent claims 23-28 and 36 limit the anti-CD20/CD3 TCB to a trivalent TCB comprising a second anti-CD20 antigen binding domain and/or an Fc domain composed of a first and a second subunit.
Dependent claims 24-28 and 36 limit the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains, to that wherein (i) first antigen binding moiety is a crossover Fab molecule wherein either the variable or the constant regions of the Fab light chain and the Fab heavy chain are exchanged; (ii) the second anti-CD20 antigen binding domain comprises HCDRs1-3 as SEQ ID NOs: 12-14, respectively, and LCDRs1-3 as SEQ ID NOs: 15-17, respectively; (iii) wherein the CD20 binding moieties are each a Fab molecule; (iv) wherein the first CD20 antigen binding moiety is fused at the C-terminus of the Fab heavy chain to the N-terminus of the Fab heavy chain of the CD3 antigen binding moiety, and the CD3 antigen binding moiety is fused at the C-terminus of the Fab heavy chain to the N-terminus of the first subunit of the Fc domain, and (v) wherein the second CD20 antigen binding moiety is fused at the C-terminus of the Fab heavy chain to the N-terminus of the second subunit of the Fc domain.
Dependent claim 25 the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains of claim 24 to that wherein the first antigen binding domain that binds CD3 comprises a VH amino acid sequence of at least about 95% identical to SEQ ID NOs:10 and VL amino acid sequence of at least about 95% identical to SEQ ID NOs: 11, and the second and third antigen binding domains which bind CD20 both comprise VH amino acid sequence of at least about 95% identical to SEQ ID NOs: 18 and VL amino acid sequence of at least about 95% identical to SEQ ID NOs: 19.
Claim 26 limits the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains of claim 24 to that wherein the CD3 antigen binding moiety of the T cell bispecific antibody is a crossover Fab molecule wherein the variable regions of the Fab light chain and the Fab heavy chain are exchanged, and wherein the CD20 binding moieties of the T cell bispecific antibody are conventional Fab molecules wherein the constant domain CL the amino acid at position 124 is substituted independently by lysine (K) (numbering according to Kabat) and the amino acid at position 123 is substituted independently by arginine (R) (numbering according to Kabat) and in the constant domain CH1 the amino acid at position 147 is substituted independently by glutamic acid (E) (numbering according to Kabat EU index) and the amino acid at position 213 is substituted independently by glutamic acid (E) (numbering according to Kabat EU index).
Claim 27 limits the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains of claim 24 to that wherein the Fc domain of the T cell bispecific antibody comprises a modification promoting the association of the first and the second subunit of the Fc domain.
Dependent claim 28 the trivalent anti-CD20/CD3 TCB comprising one CD3 antigen binding domain and two anti-CD20 antigen binding domains of claim 24 to glofitamab.
Claim 36 limits the Fab molecule for each of the CD20 antigen binding moieties of claim 24 to a conventional Fab molecule.
The combined teachings of Khadka et al. in view of Zhang pertaining to claims 3 and 18-20, and the rationale for combining them are outlined in the 103 rejection above.
The combined reference teachings do not teach that the T cell engager is glofitamab. It is noted that glofitamab comprises all of the features recited in claims 21-27 and 36.
Hutchings et al. teach that method of treating relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL) with glofitamab is a T-cell–engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells (e.g. see Abstract). Hutchings et al. also teach that glofitamab (RO7082859) is a novel T-cell–engaging, bispecific, full-length antibody that has a longer half-life compared with non–Fc-bearing bispecific T-cell engagers (e.g. see paragraph spanning pages 1959 and 1960). The 2:1 configuration enables bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells. Its CD3-binding region is fused to one of the CD20-binding regions in a head-to-tail manner via a flexible linker for improved target-effector cell binding. This endows glofitamab with superior in vitro potency versus other CD20-CD3 bispecific antibodies with a 1:1 configuration and leads to profound antitumor efficacy in preclinical DLBCL models. CD20 bivalency preserves this potency in the presence of competing anti-CD20 antibodies, providing the opportunity for pre- or co-treatment with these agents.
Hutchings et al. also teach that glofitamab induces CRS which was managed by moderate use of steroids or tocilizumab (e.g. see page 1968, left column, third paragraph).
It is noted that the Applicant has disclosed that glofitamab is also known as CD20-TCB which comprises SEQ ID NOs: 4-23 (e.g. see page 2, lines 1-6; and page 47, lines 10-15).
It is further noted that Strohl teaches that glofitamab (also known as RG6026) is a humanized heterodimeric, trivalent, bispecific (“2:1”) IgG1κ/λ-based antibody with two combining sites targeting CD20 and one targeting CD3ε (e.g. see page 142, left column, sixth paragraph; Table 1, #4; and Figure 3D, copied below). This configuration, with proper cognate heavy/light chain pairing, is achieved via cross-over, chain-swapping technology combined with an asymmetric silenced Fc generated using a modified version of knobs-into-holes technology. Strohl also teaches that the CH1 domains of the CD20 antigen binding domains comprise the K149E and K215E point mutations which correspond to positions 147 and 213, respectively, in instant claim 25 and the CL domains of the CD20 antigen binding domains comprise the E128R and Q129K point mutations which correspond to positions 123 and 124, respectively, in instant claim 25 (e.g. see page 142, left column, sixth paragraph; Table 1, #4; and Figure 3D, copied below).
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Figure 3D from Strohl 2024 (Antib Ther. 7(2):132–156)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined teachings of Khadka et al. in view of Zhang as applied to claims 3 and 18-20, and incorporate the teachings of Hutchings et al. to include that that the T cell engager is glofitamab. This is because glofitamab has already proven successful in a methods of treating R/R B-NHL and DLBCL (Hutchings et al.).
It is noted and evidenced by the instant specification and Strohl that glofitamab is a trivalent, bispecific (“2:1”) IgG1κ/λ-based antibody with two combining sites targeting CD20 and one targeting CD3ε. The configuration of glofitamab, with proper cognate heavy/light chain pairing, is achieved by cross-over, chain-swapping technology combined with an asymmetric silenced Fc generated using a modified version of knobs-into-holes technology. Furthermore, glofitamab comprises glutamine residue substitutions at positions 147 and 213 of the CH1 domains of each of the CD20 antigen binding domains and an arginine residue substitution and a lysine residue substitution as positions 123 and 124 of the CL domains of each of the CD20 antigen binding domains. Therefore, glofitamab comprises all of the features recited in claims 21-28 and 36.
Given that glofitamab has been successfully applied in methods of treating R/R B-NHL and DLBCL and that it induces CRS which can be managed by moderate use of steroids or tocilizumab; it would have been obvious to a skilled artisan to specifically apply glofitamab as the T cell engager in the method of treating a disease with a combination of a T cell engager and an NLRP3 inhibitor as taught by Khadka et al. in view of Zhang with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 3, 4, 10-20, 29-32, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 11,718,680 (the ‘680 Patent) in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592).
The instant claims are drawn to a method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and(b) the administration of an NLRP3 inhibitor to the individual.
The claims in the ‘680 Patent are drawn to a method for treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject, wherein the method comprises administering to the subject an effective amount of an anti-CD20/anti-CD3 bispecific antibody and a 4-1BB agonist.
In terms of the instantly claimed disease and T cell engager, it is noted that the method of treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject in the ‘680 Patent is a species of the generic method of treating a disease comprising administering a T cell engaging agent in an individual. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29, USPQ2d 2010 (Fed. Cir. 1993).
However, the claims in the ‘680 Patent differ from the instant invention by failing to recite that the method comprises administering an NLRP3 inhibitor in combination with the T cell engaging agent.
The teachings of Khadka et al. and Zhang are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the ‘680 Patent and to incorporate the teachings of Khadka et al. and Zhang to include administering an NLRP3 inhibitor in combination with the T cell engaging agent in the method of treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject. This is because T cell-engaging immunotherapies, such as the one claimed by the ‘680 Patent, are prone to varying degrees of toxicities (or adverse effects), including cytokine release syndrome (CRS), and in order to ensure the success of these promising and revolutionary therapies, therapeutic management of CRS is essential (Khadka et al.).
Given that T cell-engaging immunotherapies are prone to varying degrees of toxicities including CRS which limit their therapeutic efficacy (Khadka et al.), strategies to ensure the success of T cell-engaging immunotherapies include therapeutic management of CRS (Khadka et al.), and NLRP3 inhibitors are used to treat NRLP3 inflammasome-associated diseases such as CRS (Zhang); it be obvious to a skilled artisan to modify the method for treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject taught by the ‘680 Patent to further include an NLRP3 inhibitor to be used in combination with the T cell engager with a reasonable expectation of success.
In view of Khadka et al.’s teachings, a skilled artisan would reasonably anticipate that in developing a method for treating a disease with a T cell engager, the efficacy of said treatment would be limited by CRS. Therefore, it would be obvious to a skilled artisan to mitigate said CRS in said method by administering an NLRP3 inhibitor, which is known to treat T cell engager-induced CRS, in combination with the T cell engager with a reasonable expectation of success.
Regarding the limitations “wherein the administration of the NLRP3 inhibitor prevents or mitigates an adverse effect related to the administration of the T cell engaging agent” (claim 4), “wherein the administration of the NLRP3 inhibitor inhibits an adverse effect related to the administration of the T cell engaging agent” (claim 10) “wherein the inhibition to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 12), and “wherein the administration of the NLRP3 inhibitor does not inhibit a desired effect related to the administration of the T cell engaging agent” (claim 11) “wherein the inhibition is a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 32); the ’680 Patent, Khadka et al., and Zhang are silent on these properties.
However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are 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).
Although the ’680 Patent, Khadka et al., and Zhang are silent with regard to the NLRP3 inhibitor having the properties recited in claims 4, 10-12, and 32, it is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the NLRP3 inhibitor taught by Zhang would have the claimed properties recited in claims 4, 10-12, and 32.
When a claim recites using an old composition or structure (e.g., an NLRP3 inhibitor) and the use is directed to a result or property of that composition or structure (properties recited in claims 4, 10-12, and 32) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The properties recited in claims 4, 10-12, and 32 flow naturally from the teachings of the prior art. (citing Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)).
An obvious formulation cannot become nonobvious simply by measuring and claiming an activity of the formulation in a particular context, “because ‘[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property.’” Persion Pharm., slip op. at 13 (Fed. Cir. Dec. 27, 2019) (citing Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012)); see also Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 249 (1945) (“It is not invention to perceive that the product which others had discovered had qualities they failed to detect.”).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Regarding the administration steps “wherein the administration of the NLRP3 inhibitor is upon manifestation of the adverse effect in the individual” (claim 14), “wherein the administration of the NLRP3 inhibitor is before administration of the T cell engaging agent, intermittent, and orally” (claim 15), “wherein the administration of the NLRP3 inhibitor is associated with the first administration of the T cell engaging agent, wherein the administration of the NLRP3 inhibitor is prior to the first administration of the T cell engaging agent” (claim 16), and “wherein the administration of the T cell engaging agent is the first administration of the T cell engaging agent to the individual” (claim 17); the ’680 Patent, Khadka et al., and Zhang are silent on these administration steps.
However, determination of the optimal intervals of treatment and the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. The duration of treatment, the effective dosages, and like factors are well within the knowledge and expertise of the medical practitioner.
It would be obvious to one of ordinary skill in the art at the time Applicants' invention was filed to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would be routinely determined and optimized in the pharmaceutical art. Further, if there are any differences between Applicant’s claimed method and that suggested by the teachings of the prior art, the differences would appear to be minor in nature. Although the prior art do not teach all the various permutations of interval ranges as recited in claims 14-17, it would be conventional and within the skill of the art to identify the optimal administration steps. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). See MPEP §§ 2144.05 part II A.
Therefore, the claims in the ‘680 Patent would render the instant claims obvious.
Claims 3, 4, 10-20, 29-32, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims in the following U.S. Patent and Applications in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592) for similar reasons as the NSDP rejection to the ‘680 Patent above.
The instant claims are drawn to a method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and(b) the administration of an NLRP3 inhibitor to the individual.
Claims 1-52 of U.S. Patent No. 10,596,257 are drawn to methods for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of an anti-PD-L1 antagonist antibody and an anti-CEA/anti-CD3 bispecific antibody; and methods of enhancing immune function in an individual having cancer comprising administering an effective amount of an anti-PD-L1 antagonist antibody and an anti-CEA/anti-CD3 bispecific antibody.
Claims 1-28 of U.S. Patent No. 11,013,801 are drawn to a method of treating a carcinoembryonic antigen (CEA)-expressing cancer in a subject, the method comprising a treatment regimen comprising administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CEA; and a method of treating a CD20-positive B-cell disorder in a subject, the method comprising a treatment regimen comprising administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CD20.
Claims 26-32 of U.S. Application No. 18/347,362 are drawn to a method for treating a CD20 expressing cancer in a subject comprising administering to the subject an effective amount of an anti-CD20/anti-CD3 antibody and an effective amount of an anti-PD 1/anti-LAG3 bispecific antibody.
Claims 50, 51, 53, and 54 of U.S. Application No. 18/786,187 are drawn to a method of treating an individual who has a HER2-expressing cancer comprising administering to the individual a T-cell activating anti-CD3 bispecific antibody.
Claims 1-20 of U.S. Patent No. 10,781,262 are drawn to a method for treating or delaying progression of a cancer in an individual comprising administering to the individual an effective amount of an anti-CD3 T cell activating bispecific antigen-binding molecule and a PD-1 axis binding antagonist antibody; and a method of enhancing immune function in an individual having a FolR1-positive cancer comprising administering to the individual an effective amount of a combination of: (a) a T cell activating bispecific antigen-binding molecule specific for FolR1 and CD3.
Claim 25 of U.S. Application No. 18/493,659 is drawn to a method of treating a disease, in an individual, comprising administration of a T-cell activating agent, such as an antibody that binds to CD3.
Claims 10-12, 35, 36, 39, and 40 of U.S. Patent No. 12,098,213 are drawn to a method of treating an HLA-A2/WT1-expressing cancer in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising an anti-CD3 bispecific antigen binding molecule.
Claims 43 of U.S. Patent No. 12,629,419 are drawn to a method of treating an HLA-A2/WT1-expressing cancer in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising an anti-CD3 bispecific antigen binding molecule.
Claims 1-41 of U.S. Patent No. 12,629,419 are drawn to a method for preventing or mitigating an adverse effect related to the administration of a T cell bispecific antibody to an individual, comprising administering an anti-CD3 T cell bispecific antibody.
Claims 3, 6, 61-99, 107-114, 116-122, 126-127, 130, and 131 of U.S. Application No. 17/448,729 are drawn to a method for treatment of a cancer or an autoimmune disease in an individual, wherein said method comprises the administration of a T cell bispecific antibody to the individual, wherein the T cell bispecific antibody comprises an Fc domain composed of a first and a second subunit; and a method for preventing or mitigating an adverse effect related to the administration of a T cell bispecific antibody to an individual.
Claims 1 and 5-28 of U.S. Application No. 18/309,582 are drawn to methods of treating an individual having a cancer comprising administering to the individual an effective amount of a CEA CD3 bispecific antibody.
Claims 102-124 of U.S. Application No. 19/016,060 are drawn to a method of treating a subject having a relapsed or refractory (R/R) multiple myeloma (MM), the method comprising administering to the subject a bispecific antibody that binds to Fc receptor-homolog 5 (FcRH5) and cluster of differentiation 3 (CD3) and a method of treating a subject having a relapsed or refractory (R/R) multiple myeloma (MM), wherein the subject has previously received a B cell maturation factor (BCMA)-targeting therapeutic agent, the method comprising administering to the subject a bispecific antibody that binds to Fc receptor-homolog 5 (FcRH5) and cluster of differentiation 3 (CD3).
Claims 3-13 and 15-19 of U.S. Application No. 18/668,810 are drawn to a method of treating a tyrosinase-related protein 1 (TYRP1)- expressing cancer in an individual comprising administering to said individual a therapeutically effective amount of an anti-TYRP1/anti-CD3 bispecific antibody.
Claims 62, 63, and 64-66 of U.S. Application No. 18/421,912 are drawn to methods of treating a disease in an individual, comprising administering to the individual an effective amount of an antibody that binds to CD3 and Colony stimulating factor 1 receptor (CSF1R), comprising a first antigen binding domain that binds CD3 and a second antigen binding domain that binds to CSF1R.
Claims 23-35 of U.S. Application No. 19/310,373 are drawn to a method for treating an HLA-G expressing cancer in a subject comprising administering to the subject an effective amount of an anti-HLA-G/anti-CD3 antibody and an effective amount of an anti-PD1/anti-LAG3 bispecific antibody.
Claim 5 of U.S. Patent No. 12,065,502 is drawn to a method of treatment, comprising administering to a subject who has cancer a pharmaceutical formulation comprising: 20 to 50 mg/ml of a CEA CD3 bispecific antibody.
Claims 116-145 of U.S. Application No. 19,027,113 are drawn to a method of treating a subject having a multiple myeloma (MM) with a high-risk cytogenetic feature, the method comprising administering to the subject (i) a bispecific antibody that binds to fragment crystallizable receptor-like 5 (FcRH5) and cluster of differentiation 3 (CD3); and methods of method of treating a subject having an MM with a high-risk cytogenetic feature, the method comprising administering to the subject cevostamab and lenalidomide.
Claims 29 and 34 of U.S. Application No. 18/063,459 are drawn to a method of treating a cancer in an individual, comprising administering to said individual an effective amount of an antibody that binds to CD3 and PLAP; and a method of treating an autoimmune disease in an individual, comprising administering to said individual an effective amount of an antibody that binds to CD3 and PLAP.
Claims 31-33, 45, and 61-64 of U.S. Application No. 18/066,526 are drawn to methods of treating a cancer in an individual comprising administering to the subject a bispecific antibody that binds to CD3 and Folate receptor 1 (FoIRi).
Claims 81-86 of U.S. Application No. 19/093,051 are drawn to methods of treating or delaying progression of a disease, or stimulating an immune response or function, in an individual, comprising administering to said individual a therapeutically effective amount of an anti-CD3 bispecific molecule.
Claims 14 and 15 of U.S. Patent No. 10,253,104 are drawn to a method of treatment of a plasma cell disorder in a subject comprising administering an effective amount of a composition comprising a bispecific bi- or trivalent antibody specifically binding to two targets which are the extracellular domain of human B cell maturation antigen (BCMA) and human CD3ε (CD3) to said subject; and a method of treatment of Multiple Myeloma comprising administering an effective amount of a composition comprising a bispecific bi- or trivalent antibody specifically binding to two targets which are the extracellular domain of human B cell maturation antigen (BCMA) and human CD3ε (CD3) to said subject.
Claims 1-9 of U.S. Patent No. 12,565,530 are drawn to a method for treating cancer in a subject, wherein the method comprises administering to the subject an effective amount of a T-cell activating anti-carcinoembryonic antigen (CEA)/anti-CD3 bispecific antibody.
Claims 42, 46, and 47 of U.S. Application No. 18/069,847 are drawn to a method of treating an epithelial cancer in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule; a method of treating a squamous cell carcinoma in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule; and a method of treating cancer in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule.
Claims 1-5 of U.S. Patent No. 9,963,513 are drawn to a method of treating multiple myeloma (MM) comprising administering a bispecific antibody specifically binding to human B cell maturation factor (BCMA) and CD3 to a subject in need thereof.
Claims 50 and 51 of U.S. Application No. 18/066,529 are drawn to a of treating a disease in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising the protease-activatable anti-CD3 T cell activating bispecific molecule.
Claims 1-39 of U.S. Patent No. 10,781,258 are drawn to a method of treating a CEA-expressing cancer in an individual, the method comprising administering to the individual a therapeutically effective amount of a composition comprising an anti-CD3 T cell activating bispecific antigen-binding molecule in a pharmaceutically acceptable form; and a method for inducing lysis of a CEA-expressing tumor target cell, the method comprising contacting the CEA-expressing tumor target cell with an anti-CD3 T cell activating bispecific antigen-binding molecule comprising.
Claims 15 and 20 of U.S. Application No. 18/772,922 are drawn to methods of treating cancer in a patient, the method comprising administering to the patient an effective amount of a multispecific antibody that binds to human HLA-G and to human CD3.
Claims 27-51 of U.S. Application No. 18/742,449 are drawn to a method of treating a MAGE-A4-expressing cancer in an individual, comprising administering to the individual an HLA-A2/MAGE-A4 x CD3 bispecific antibody.
Claims 27-51 of U.S. Application No. 18/646,492 are drawn to a method of treating a WT1-expressing cancer in an individual, comprising administering to the individual an HLA-A2/WT1 x CD3 bispecific antibody.
Claim 22 of U.S. Application No. 18/979,221 is drawn to a method of treatment comprising the administration of an anti-CD3 multimeric polypeptide to a patient in need of such treatment.
Claims 1-16 of U.S. Patent No. 11,672,858 are drawn to a method of treating a TYRP-1-expressing cancer in a human individual having a TYRP-1-expressing cancer, the method comprising administering to the individual an effective amount of an anti-CD3 bispecific antibody molecule.
Claims 1-19 of U.S. Application No. 19/136,536 are drawn to methods of treating a cancer in a patient, the method comprising administering a combination therapy comprising a CD47 blocking agent and an anti-CD20/ anti-CD3 bispecific antibody to the patient.
Claim 3 of U.S. Application No. 19/319,680 is drawn to a method of treating cancer in an individual comprising administering to said individual an anti- EGFRvill/anti-CD3 bispecific antibody in combination with a tumor-targeted 4-1BB agonist.
Claims 5, 7-14, 16, and 18-26 of U.S. Application No. 19/325,175 are drawn to a method for treating cancer in an individual comprising administering to the individual an effective amount of an anti-HLA-G/anti-CD3 bispecific antibody.
In terms of the instantly claimed disease and T cell engager, it is noted that the methods in the above Patents and Applications are species of the generic method of treating a disease comprising administering a T cell engaging agent in an individual. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29, USPQ2d 2010 (Fed. Cir. 1993).
However, the claims in the above Patents and Applications differ from the instant invention by failing to recite that the method comprises administering an NLRP3 inhibitor in combination with the T cell engaging agent.
The teachings of Khadka et al. and Zhang are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the above Patents and Applications and to incorporate the teachings of Khadka et al. and Zhang to include administering an NLRP3 inhibitor in combination with the T cell engaging agent in the method of treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject. This is because T cell-engaging immunotherapies, such as the one claimed by the above Patents and Applications, are prone to varying degrees of toxicities (or adverse effects), including cytokine release syndrome (CRS), and in order to ensure the success of these promising and revolutionary therapies, therapeutic management of CRS is essential (Khadka et al.).
Given that T cell-engaging immunotherapies are prone to varying degrees of toxicities including CRS which limit their therapeutic efficacy (Khadka et al.), strategies to ensure the success of T cell-engaging immunotherapies include therapeutic management of CRS (Khadka et al.), and NLRP3 inhibitors are used to treat NRLP3 inflammasome-associated diseases such as CRS (Zhang); it be obvious to a skilled artisan to modify the methods taught by the above Patents and Applications to further include an NLRP3 inhibitor to be used in combination with the T cell engager with a reasonable expectation of success.
In view of Khadka et al.’s teachings, a skilled artisan would reasonably anticipate that in developing a method for treating a disease with a T cell engager, the efficacy of said treatment would be limited by CRS. Therefore, it would be obvious to a skilled artisan to mitigate said CRS in said method by administering an NLRP3 inhibitor, which is known to treat T cell engager-induced CRS, in combination with the T cell engager with a reasonable expectation of success.
Regarding the limitations “wherein the administration of the NLRP3 inhibitor prevents or mitigates an adverse effect related to the administration of the T cell engaging agent” (claim 4), “wherein the administration of the NLRP3 inhibitor inhibits an adverse effect related to the administration of the T cell engaging agent” (claim 10) “wherein the inhibition to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 12), and “wherein the administration of the NLRP3 inhibitor does not inhibit a desired effect related to the administration of the T cell engaging agent” (claim 11) “wherein the inhibition is a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 32); the above Patents and Applications, Khadka et al., and Zhang are silent on these properties.
However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are 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).
Although the above Patents and Applications, Khadka et al., and Zhang are silent with regard to the NLRP3 inhibitor having the properties recited in claims 4, 10-12, and 32, it is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the NLRP3 inhibitor taught by Zhang would have the claimed properties recited in claims 4, 10-12, and 32.
When a claim recites using an old composition or structure (e.g., an NLRP3 inhibitor) and the use is directed to a result or property of that composition or structure (properties recited in claims 4, 10-12, and 32) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The properties recited in claims 4, 10-12, and 32 flow naturally from the teachings of the prior art. (citing Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)).
An obvious formulation cannot become nonobvious simply by measuring and claiming an activity of the formulation in a particular context, “because ‘[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property.’” Persion Pharm., slip op. at 13 (Fed. Cir. Dec. 27, 2019) (citing Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012)); see also Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 249 (1945) (“It is not invention to perceive that the product which others had discovered had qualities they failed to detect.”).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Regarding the administration steps “wherein the administration of the NLRP3 inhibitor is upon manifestation of the adverse effect in the individual” (claim 14), “wherein the administration of the NLRP3 inhibitor is before administration of the T cell engaging agent, intermittent, and orally” (claim 15), “wherein the administration of the NLRP3 inhibitor is associated with the first administration of the T cell engaging agent, wherein the administration of the NLRP3 inhibitor is prior to the first administration of the T cell engaging agent” (claim 16), and “wherein the administration of the T cell engaging agent is the first administration of the T cell engaging agent to the individual” (claim 17); the above Patents and Applications, Khadka et al., and Zhang are silent on these administration steps.
However, determination of the optimal intervals of treatment and the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. The duration of treatment, the effective dosages, and like factors are well within the knowledge and expertise of the medical practitioner.
It would be obvious to one of ordinary skill in the art at the time Applicants' invention was filed to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would be routinely determined and optimized in the pharmaceutical art. Further, if there are any differences between Applicant’s claimed method and that suggested by the teachings of the prior art, the differences would appear to be minor in nature. Although the prior art do not teach all the various permutations of interval ranges as recited in claims 14-17, it would be conventional and within the skill of the art to identify the optimal administration steps. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). See MPEP §§ 2144.05 part II A.
Therefore, the claims in the above Patents and Applications would render the instant claims obvious.
Claims 3, 4, 10-33, 36, and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 6, 19, 24, 25, 28, 29, 39, 40, 44, 45, 48, 58, 60, 71, 72, 74, 95, 97, and 113-120 of U.S. Application No. 19/175,703 (the ‘730 Application) in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592).
The instant claims are drawn to a method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and(b) the administration of an NLRP3 inhibitor to the individual.
The claims in the ‘730 Application are drawn to methods for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a human patient in need thereof, comprising administering to the human patient an effective amount of glofitamab; and a method of reducing the incidence of CRS events or the likelihood of a CRS event in a CD20-positive B cell proliferative disorder patient population treated with glofitamab.
In terms of the instantly claimed disease and T cell engager, it is noted that the methods for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a human patient in need thereof, comprising administering to the human patient an effective amount of glofitamab and the method of reducing the incidence of CRS events or the likelihood of a CRS event in a CD20-positive B cell proliferative disorder patient population treated with glofitamab in the ‘730 Application is a species of the generic method of treating a disease comprising administering a T cell engaging agent in an individual. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29, USPQ2d 2010 (Fed. Cir. 1993).
However, the claims in the ‘730 Application differ from the instant invention by failing to recite that the method comprises administering an NLRP3 inhibitor in combination with the T cell engaging agent.
The teachings of Khadka et al. and Zhang are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the ‘730 Application and to incorporate the teachings of Khadka et al. and Zhang to include administering an NLRP3 inhibitor in combination with the T cell engaging agent in the methods for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a human patient in need thereof, comprising administering to the human patient an effective amount of glofitamab and the method of reducing the incidence of CRS events or the likelihood of a CRS event in a CD20-positive B cell proliferative disorder patient population treated with glofitamab. This is because T cell-engaging immunotherapies, such as the one claimed by the ‘680 Patent, are prone to varying degrees of toxicities (or adverse effects), including cytokine release syndrome (CRS), and in order to ensure the success of these promising and revolutionary therapies, therapeutic management of CRS is essential (Khadka et al.).
Given that T cell-engaging immunotherapies are prone to varying degrees of toxicities including CRS which limit their therapeutic efficacy (Khadka et al.), strategies to ensure the success of T cell-engaging immunotherapies include therapeutic management of CRS (Khadka et al.), and NLRP3 inhibitors are used to treat NRLP3 inflammasome-associated diseases such as CRS (Zhang); it be obvious to a skilled artisan to modify the methods for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a human patient in need thereof, comprising administering to the human patient an effective amount of glofitamab and the method of reducing the incidence of CRS events or the likelihood of a CRS event in a CD20-positive B cell proliferative disorder patient population treated with glofitamab taught by the ‘730 Application to further include an NLRP3 inhibitor to be used in combination with the T cell engager with a reasonable expectation of success.
In view of Khadka et al.’s teachings, a skilled artisan would reasonably anticipate that in developing a method for treating a disease with a T cell engager, the efficacy of said treatment would be limited by CRS. Therefore, it would be obvious to a skilled artisan to mitigate said CRS in said method by administering an NLRP3 inhibitor, which is known to treat T cell engager-induced CRS, in combination with the T cell engager with a reasonable expectation of success.
Regarding the limitations “wherein the administration of the NLRP3 inhibitor prevents or mitigates an adverse effect related to the administration of the T cell engaging agent” (claim 4), “wherein the administration of the NLRP3 inhibitor inhibits an adverse effect related to the administration of the T cell engaging agent” (claim 10) “wherein the inhibition to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 12), and “wherein the administration of the NLRP3 inhibitor does not inhibit a desired effect related to the administration of the T cell engaging agent” (claim 11) “wherein the inhibition is a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 32); the ‘730 Application, Khadka et al., and Zhang are silent on these properties.
However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are 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).
Although the ‘730 Application, Khadka et al., and Zhang are silent with regard to the NLRP3 inhibitor having the properties recited in claims 4, 10-12, and 32, it is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the NLRP3 inhibitor taught by Zhang would have the claimed properties recited in claims 4, 10-12, and 32.
When a claim recites using an old composition or structure (e.g., an NLRP3 inhibitor) and the use is directed to a result or property of that composition or structure (properties recited in claims 4, 10-12, and 32) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The properties recited in claims 4, 10-12, and 32 flow naturally from the teachings of the prior art. (citing Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)).
An obvious formulation cannot become nonobvious simply by measuring and claiming an activity of the formulation in a particular context, “because ‘[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property.’” Persion Pharm., slip op. at 13 (Fed. Cir. Dec. 27, 2019) (citing Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012)); see also Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 249 (1945) (“It is not invention to perceive that the product which others had discovered had qualities they failed to detect.”).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Regarding the administration steps “wherein the administration of the NLRP3 inhibitor is upon manifestation of the adverse effect in the individual” (claim 14), “wherein the administration of the NLRP3 inhibitor is before administration of the T cell engaging agent, intermittent, and orally” (claim 15), “wherein the administration of the NLRP3 inhibitor is associated with the first administration of the T cell engaging agent, wherein the administration of the NLRP3 inhibitor is prior to the first administration of the T cell engaging agent” (claim 16), and “wherein the administration of the T cell engaging agent is the first administration of the T cell engaging agent to the individual” (claim 17); the ‘730 Application, Khadka et al., and Zhang are silent on these administration steps.
However, determination of the optimal intervals of treatment and the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. The duration of treatment, the effective dosages, and like factors are well within the knowledge and expertise of the medical practitioner.
It would be obvious to one of ordinary skill in the art at the time Applicants' invention was filed to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would be routinely determined and optimized in the pharmaceutical art. Further, if there are any differences between Applicant’s claimed method and that suggested by the teachings of the prior art, the differences would appear to be minor in nature. Although the prior art do not teach all the various permutations of interval ranges as recited in claims 14-17, it would be conventional and within the skill of the art to identify the optimal administration steps. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). See MPEP §§ 2144.05 part II A.
Therefore, the claims in the ‘730 Application would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 3, 4, 10-33, 36, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims in the following U.S. Patents and Applications in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592) for similar reasons as the NSDP rejection to the claims in the ‘730 Application.
The instant claims are drawn to a method for treatment of a disease in an individual, wherein said method comprises (a) the administration of a T cell engaging agent to the individual, and(b) the administration of an NLRP3 inhibitor to the individual.
Claims 1-41 of U.S. Patent No. 10,611,841 are drawn to methods of treating a CD20-expressing cancer in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising a T cell activating bispecific antigen-binding molecule in a pharmaceutically acceptable form, the T cell activating bispecific antigen-binding molecule comprising: (a) a first Fab molecule which specifically binds to CD20 and (b) a second Fab molecule which specifically binds to CD3; methods of inducing lysis of a human CD20-expressing tumor target cell, comprising contacting the target cell with a T cell activating bispecific antigen-binding molecule in the presence of a T cell, the T cell activating bispecific antigen-binding molecule comprising: (a) a first Fab molecule which specifically binds to CD20 and (b) a second Fab molecule which specifically binds to CD3.
It is noted that the T cell activating bispecific antigen-binding molecule of the ‘841 Patent comprises the same structure as glofitamab (CDRs and CH1 and CL amino acid substitutions).
Claims 1, 3, 6, 8, 9, 12, 13, 16, 19, 20, 26, 27, 57-59, 61-63, 96, 99, 104, and 131-133 of U.S. Application No. 17/733,909 are drawn to a method of treating a subject having a CD20-positive B cell proliferative disorder comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle; a method of treating a subject having a non-Hodgkin lymphoma comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle; a method of treating a subject having a diffuse large B cell lymphoma comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle; method of treating a subject having a diffuse large B cell lymphoma comprising administering to the subject glofitamab in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle.
It is noted that the anti-CD20/anti-CD3 bispecific antibody of the ‘909 Application comprises the same structure as glofitamab (CDRs and CH1 and CL amino acid substitutions) or is glofitamab.
Claim 29 of U.S. Application No. 18/347,362 is drawn to a method for treating a CD20 expressing cancer in a subject comprising administering to the subject an effective amount of an anti-CD20/anti-CD3 antibody and an effective amount of an anti-PD 1/anti-LAG3 bispecific antibody, wherein the anti- CD20/anti-CD3 bispecific antibody is glofitamab.
Claims 30 and 36-55 of U.S. Application No. 18/299,877 are drawn to a method of treating or delaying the progression of a cell proliferative disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a liquid pharmaceutical composition comprising glofitamab; and methods of treating an R/R DLBCL NOS or trFL in a subject in need thereof, the method comprising intravenously administering to the subject an effective amount of glofitamab.
Claims 1, 2, 4-6, 8, 9, 12, 16, 18, 19, 21, 22, 24, and 30-35 of U.S. Application No. 18/923,857 are drawn to a method of treating previously untreated circulating tumor DNA (ctDNA) high risk diffuse large B-Cell Lymphoma in an individual in need thereof, comprising administering a bispecific antibody targeting CD3 and CD20.
It is noted that the anti-CD20/anti-CD3 bispecific antibody of the ‘857 Application comprises the same structure as glofitamab (CDRs and CH1 and CL amino acid substitutions) or is glofitamab.
Claims 1-4, 6, 8-10, 14, 19, 21, 22, and 25 of U.S. Application No. 18/188,168 are drawn to a method of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject an effective amount of glofitamab.
Claims 100-106 and 123-125 of U.S. Application No. 17/448,729 are drawn to a method for treatment of a cancer or an autoimmune disease in an individual, wherein said method comprises the administration of a T cell bispecific antibody to the individual, wherein the T cell bispecific antibody comprises an Fc domain composed of a first and a second subunit, wherein the target cell antigen is CD20; and a method for preventing or mitigating an adverse effect related to the administration of a T cell bispecific antibody to an individual, wherein the target cell antigen is CD20.
It is noted that the anti-CD20/anti-CD3 bispecific antibody of the ‘729 Application comprises the same structure as glofitamab (CDRs and CH1 and CL amino acid substitutions) or is glofitamab.
Claims 1-28 of U.S. Patent No. 12,195,547 are drawn to methods of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject glofitamab; and a method of treating a population of subjects having a relapsed and/or refractory NHL comprising administering to the subjects glofitamab.
Claims 167-205 of U.S. Patent No. 18/964,055 are drawn to methods of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject glofitamab.
Claims 1, 7, 15, 16, 19, 28, 29, 33, 39, 42, 45, 47, 56, 58, 60, 63-65, 69, 89, 90, 93, 94, 97, 105, and 106 of U.S. Application No. 19/372,448 are drawn to methods for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a human individual in need thereof, comprising administering to the human individual an effective amount of glofitamab.
In terms of the instantly claimed disease and T cell engager, it is noted that the methods in the above Patents and Applications are a species of the generic method of treating a disease comprising administering a T cell engaging agent in an individual. It has been held that a generic invention is “anticipated” by a “species” within the scope of the generic invention. See In re Goodman, 29, USPQ2d 2010 (Fed. Cir. 1993).
However, the claims in the above Patents and Applications differ from the instant invention by failing to recite that the method comprises administering an NLRP3 inhibitor in combination with the T cell engaging agent.
The teachings of Khadka et al. and Zhang are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the above Patents and Applications and to incorporate the teachings of Khadka et al. and Zhang to include administering an NLRP3 inhibitor in combination with the T cell engaging agent in the claimed methods. This is because T cell-engaging immunotherapies, such as the one claimed by the above Patents and Applications, are prone to varying degrees of toxicities (or adverse effects), including cytokine release syndrome (CRS), and in order to ensure the success of these promising and revolutionary therapies, therapeutic management of CRS is essential (Khadka et al.).
Given that T cell-engaging immunotherapies are prone to varying degrees of toxicities including CRS which limit their therapeutic efficacy (Khadka et al.), strategies to ensure the success of T cell-engaging immunotherapies include therapeutic management of CRS (Khadka et al.), and NLRP3 inhibitors are used to treat NRLP3 inflammasome-associated diseases such as CRS (Zhang); it be obvious to a skilled artisan to modify the methods taught by the above Patents and Applications to further include an NLRP3 inhibitor to be used in combination with the T cell engager with a reasonable expectation of success.
In view of Khadka et al.’s teachings, a skilled artisan would reasonably anticipate that in developing a method for treating a disease with a T cell engager, the efficacy of said treatment would be limited by CRS. Therefore, it would be obvious to a skilled artisan to mitigate said CRS in said method by administering an NLRP3 inhibitor, which is known to treat T cell engager-induced CRS, in combination with the T cell engager with a reasonable expectation of success.
Regarding the limitations “wherein the administration of the NLRP3 inhibitor prevents or mitigates an adverse effect related to the administration of the T cell engaging agent” (claim 4), “wherein the administration of the NLRP3 inhibitor inhibits an adverse effect related to the administration of the T cell engaging agent” (claim 10) “wherein the inhibition to a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 12), and “wherein the administration of the NLRP3 inhibitor does not inhibit a desired effect related to the administration of the T cell engaging agent” (claim 11) “wherein the inhibition is a complete inhibition, or a clinically meaningful and/or statistically significant inhibition” (claim 32); the above Patents and Applications, Khadka et al., and Zhang are silent on these properties.
However, silence about a particular property does not necessarily constitute its absence. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that there is a difference between the materials, i.e., that the claims are directed to new materials and that such a difference would have been considered unexpected by one of ordinary skill in the art, that is, the claimed subject matter, if new, is unobvious. In the absence of evidence to the contrary, the burden is on the Applicant to prove that the claimed materials are 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).
Although the above Patents and Applications, Khadka et al., and Zhang are silent with regard to the NLRP3 inhibitor having the properties recited in claims 4, 10-12, and 32, it is noted that a compound and all of its properties are inseparable; they are one and the same thing (see In re Papesch, CCPA 137 USPQ 43; In re Swinehart and Sfiligoj, 169) USPQ 226 (CCPA 1971)). Therefore, in the absence of evidence to the contrary, the NLRP3 inhibitor taught by Zhang would have the claimed properties recited in claims 4, 10-12, and 32.
When a claim recites using an old composition or structure (e.g., an NLRP3 inhibitor) and the use is directed to a result or property of that composition or structure (properties recited in claims 4, 10-12, and 32) then the claim is anticipated. See MPEP 2112.02. Also, see Bristol-Myers Squibb Co. v. Ben Venue Laboratories, Inc. 58 USPQ2d 1508 (CA FC 2001); Ex parte Novitski 26 USPQ 1389 (BPAI 1993); Mehl/Biophile International Corp. V. Milgraum, 52 USPQ2d 1303 (Fed. Cir. 1999); Atlas Powder Co. V. IRECO, 51 USPQ2d 1943 (Fed. Cir. 1999).
The properties recited in claims 4, 10-12, and 32 flow naturally from the teachings of the prior art. (citing Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985 (“The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious.”), and Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of... a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer.”)).
An obvious formulation cannot become nonobvious simply by measuring and claiming an activity of the formulation in a particular context, “because ‘[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property.’” Persion Pharm., slip op. at 13 (Fed. Cir. Dec. 27, 2019) (citing Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012)); see also Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242, 249 (1945) (“It is not invention to perceive that the product which others had discovered had qualities they failed to detect.”).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Regarding the administration steps “wherein the administration of the NLRP3 inhibitor is upon manifestation of the adverse effect in the individual” (claim 14), “wherein the administration of the NLRP3 inhibitor is before administration of the T cell engaging agent, intermittent, and orally” (claim 15), “wherein the administration of the NLRP3 inhibitor is associated with the first administration of the T cell engaging agent, wherein the administration of the NLRP3 inhibitor is prior to the first administration of the T cell engaging agent” (claim 16), and “wherein the administration of the T cell engaging agent is the first administration of the T cell engaging agent to the individual” (claim 17); the above Patents and Applications, Khadka et al., and Zhang are silent on these administration steps.
However, determination of the optimal intervals of treatment and the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. The duration of treatment, the effective dosages, and like factors are well within the knowledge and expertise of the medical practitioner.
It would be obvious to one of ordinary skill in the art at the time Applicants' invention was filed to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would be routinely determined and optimized in the pharmaceutical art. Further, if there are any differences between Applicant’s claimed method and that suggested by the teachings of the prior art, the differences would appear to be minor in nature. Although the prior art do not teach all the various permutations of interval ranges as recited in claims 14-17, it would be conventional and within the skill of the art to identify the optimal administration steps. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). See MPEP §§ 2144.05 part II A.
Therefore, the claims in the above Patents and Applications would render the instant claims obvious.
Claim 9 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 11,718,680 (the ‘680 Patent) in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592), as applied to claim 3, and further in view of Schwaid and Spencer 2020 (J. Med. Chem. 64(1), 101-122).
The combined teachings of the claims of the ‘680 Patent in view of Khadka et al. and Zhang pertaining to claim 3, and the rationale for combining them are outlined in the NSDP rejection above.
The combined teachings do not teach that the NLRP3 inhibitor is specifically selnoflast.
The teachings of Schwaid and Spencer are outlined in the 103 rejection above.
It would be to one of ordinary skill in the art to modify the combined teachings the claims of the ‘680 Patent in view of Khadka et al. and Zhang as applied to claim 3, and incorporate the teachings of Schwaid and Spencer to include that the NLRP3 inhibitor is specifically selnoflast.
Given that somalix, also known as selnoflast, is a known peripherally restricted NLRP3 inhibitor; it would be obvious to a skilled artisan to specifically apply selnoflast as the NLRP3 inhibitor in the method for treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject taught by the ‘680 Patent in view of Khadka et al. in view of Zhang with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘680 Patent would render the instant claims obvious.
Claim 9 is (provisionally) rejected on the ground of nonstatutory double patenting as being unpatentable over the claims in the following U.S. Patent and Applications in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592), as applied to claim 3, and further in view of Schwaid and Spencer 2020 (J. Med. Chem. 64(1), 101-122) for similar reasons as the NSDP rejection to the ‘680 Patent above.
Claims 1-52 of U.S. Patent No. 10,596,257 are drawn to methods for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of an anti-PD-L1 antagonist antibody and an anti-CEA/anti-CD3 bispecific antibody; and methods of enhancing immune function in an individual having cancer comprising administering an effective amount of an anti-PD-L1 antagonist antibody and an anti-CEA/anti-CD3 bispecific antibody.
Claims 1-28 of U.S. Patent No. 11,013,801 are drawn to a method of treating a carcinoembryonic antigen (CEA)-expressing cancer in a subject, the method comprising a treatment regimen comprising administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CEA; and a method of treating a CD20-positive B-cell disorder in a subject, the method comprising a treatment regimen comprising administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CD20.
Claims 1, 2, 5, 6, 19, 24, 25, 28, 29, 39, 40, 44, 45, 48, 58, 60, 71, 72, 74, 95, 97, and 113-120 of U.S. Application No. 19/175,703 are drawn to methods for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a human patient in need thereof, comprising administering to the human patient an effective amount of glofitamab; and a method of reducing the incidence of CRS events or the likelihood of a CRS event in a CD20-positive B cell proliferative disorder patient population treated with glofitamab.
Claims 1-41 of U.S. Patent No. 10,611,841 are drawn to methods of treating a CD20-expressing cancer in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising a T cell activating bispecific antigen-binding molecule in a pharmaceutically acceptable form, the T cell activating bispecific antigen-binding molecule comprising: (a) a first Fab molecule which specifically binds to CD20 and (b) a second Fab molecule which specifically binds to CD3; methods of inducing lysis of a human CD20-expressing tumor target cell, comprising contacting the target cell with a T cell activating bispecific antigen-binding molecule in the presence of a T cell, the T cell activating bispecific antigen-binding molecule comprising: (a) a first Fab molecule which specifically binds to CD20 and (b) a second Fab molecule which specifically binds to CD3.
It is noted that the T cell activating bispecific antigen-binding molecule of the ‘841 Patent comprises the same structure as glofitamab (CDRs and CH1 and CL amino acid substitutions).
Claims 1, 3, 6, 8, 9, 12, 13, 16, 19, 20, 26, 27, 57-59, 61-63, 96, 99, 104, and 131-133 of U.S. Application No. 17/733,909 are drawn to a method of treating a subject having a CD20-positive B cell proliferative disorder comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle; a method of treating a subject having a non-Hodgkin lymphoma comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle; a method of treating a subject having a diffuse large B cell lymphoma comprising administering to the subject an anti-CD20/anti-CD3 bispecific antibody in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle; method of treating a subject having a diffuse large B cell lymphoma comprising administering to the subject glofitamab in a dosing regimen comprising at least a first dosing cycle and a second dosing cycle.
It is noted that the anti-CD20/anti-CD3 bispecific antibody of the ‘909 Application comprises the same structure as glofitamab (CDRs and CH1 and CL amino acid substitutions) or is glofitamab.
Claim 26-32 of U.S. Application No. 18/347,362 is drawn to a method for treating a CD20 expressing cancer in a subject comprising administering to the subject an effective amount of an anti-CD20/anti-CD3 antibody and an effective amount of an anti-PD 1/anti-LAG3 bispecific antibody.
Claims 30 and 36-55 of U.S. Application No. 18/299,877 are drawn to a method of treating or delaying the progression of a cell proliferative disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a liquid pharmaceutical composition comprising glofitamab; and methods of treating an R/R DLBCL NOS or trFL in a subject in need thereof, the method comprising intravenously administering to the subject an effective amount of glofitamab.
Claim 50, 51, 53, and 54 of U.S. Application No. 18/786,187 is drawn to a method of treating an individual who has a HER2-expressing cancer comprising administering to the individual a T-cell activating anti-CD3 bispecific antibody.
Claims 1, 2, 4-6, 8, 9, 12, 16, 18, 19, 21, 22, 24, and 30-35 of U.S. Application No. 18/923,857 are drawn to a method of treating previously untreated circulating tumor DNA (ctDNA) high risk diffuse large B-Cell Lymphoma in an individual in need thereof, comprising administering a bispecific antibody targeting CD3 and CD20.
It is noted that the anti-CD20/anti-CD3 bispecific antibody of the ‘857 Application comprises the same structure as glofitamab (CDRs and CH1 and CL amino acid substitutions) or is glofitamab.
Claims 1-4, 6, 8-10, 14, 19, 21, 22, and 25 of U.S. Application No. 18/188,168 are drawn to a method of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject an effective amount of glofitamab.
Claim 1-20 of U.S. Patent No. 10,781,262 is drawn to a method for treating or delaying progression of a cancer in an individual comprising administering to the individual an effective amount of an anti-CD3 T cell activating bispecific antigen-binding molecule and a PD-1 axis binding antagonist antibody; and a method of enhancing immune function in an individual having a FolR1-positive cancer comprising administering to the individual an effective amount of a combination of: (a) a T cell activating bispecific antigen-binding molecule specific for FolR1 and CD3.
Claim 25 of U.S. Application No. 18/493,659 is drawn to a method of treating a disease, in an individual, comprising administration of a T-cell activating agent, such as an antibody that binds to CD3.
Claims 10-12, 35, 36, 39, and 40 of U.S. Patent No. 12,098,213 are drawn to a method of treating an HLA-A2/WT1-expressing cancer in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising an anti-CD3 bispecific antigen binding molecule.
Claims 1-41 of U.S. Patent No. 12,629,419 are drawn to a method for preventing or mitigating an adverse effect related to the administration of a T cell bispecific antibody to an individual, comprising administering an anti-CD3 T cell bispecific antibody.
Claims 3, 6, 61-114, 116-128, 130, and 131 of U.S. Application No. 17/448,729 are drawn to a method for treatment of a cancer or an autoimmune disease in an individual, wherein said method comprises the administration of a T cell bispecific antibody to the individual, wherein the T cell bispecific antibody comprises an Fc domain composed of a first and a second subunit; and a method for preventing or mitigating an adverse effect related to the administration of a T cell bispecific antibody to an individual.
Claims 1 and 5-28 of U.S. Application No. 18/309,582 are drawn to methods of treating an individual having a cancer comprising administering to the individual an effective amount of a CEA CD3 bispecific antibody.
Claims 102-124 of U.S. Application No. 19/016,060 are drawn to a method of treating a subject having a relapsed or refractory (R/R) multiple myeloma (MM), the method comprising administering to the subject a bispecific antibody that binds to Fc receptor-homolog 5 (FcRH5) and cluster of differentiation 3 (CD3) and a method of treating a subject having a relapsed or refractory (R/R) multiple myeloma (MM), wherein the subject has previously received a B cell maturation factor (BCMA)-targeting therapeutic agent, the method comprising administering to the subject a bispecific antibody that binds to Fc receptor-homolog 5 (FcRH5) and cluster of differentiation 3 (CD3).
Claims 3-13 and 15-19 of U.S. Application No. 18/668,810 are drawn to a method of treating a tyrosinase-related protein 1 (TYRP1)- expressing cancer in an individual comprising administering to said individual a therapeutically effective amount of an anti-TYRP1/anti-CD3 bispecific antibody.
Claims 62, 63, and 64-66 of U.S. Application No. 18/421,912 are drawn to methods of treating a disease in an individual, comprising administering to the individual an effective amount of an antibody that binds to CD3 and Colony stimulating factor 1 receptor (CSF1R), comprising a first antigen binding domain that binds CD3 and a second antigen binding domain that binds to CSF1R.
Claims 23-35 of U.S. Application No. 19/310,373 are drawn to a method for treating an HLA-G expressing cancer in a subject comprising administering to the subject an effective amount of an anti-HLA-G/anti-CD3 antibody and an effective amount of an anti-PD1/anti-LAG3 bispecific antibody.
Claim 5 of U.S. Patent No. 12,065, 502 are drawn to a method of treatment, comprising administering to a subject who has cancer a pharmaceutical formulation comprising: 20 to 50 mg/ml of a CEA CD3 bispecific antibody.
Claims 116-145 of U.S. Application No. 19,027,113 are drawn to a method of treating a subject having a multiple myeloma (MM) with a high-risk cytogenetic feature, the method comprising administering to the subject (i) a bispecific antibody that binds to fragment crystallizable receptor-like 5 (FcRH5) and cluster of differentiation 3 (CD3); and methods of method of treating a subject having an MM with a high-risk cytogenetic feature, the method comprising administering to the subject cevostamab and lenalidomide.
Claims 29 and 34 of U.S. Application No. 18/063,459 are drawn to a method of treating a cancer in an individual, comprising administering to said individual an effective amount of an antibody that binds to CD3 and PLAP; and a method of treating an autoimmune disease in an individual, comprising administering to said individual an effective amount of an antibody that binds to CD3 and PLAP.
Claims 31-33, 45, and 61-64 of U.S. Application No. 18/066,526 are drawn to methods of treating a cancer in an individual comprising administering to the subject a bispecific antibody that binds to CD3 and Folate receptor 1 (FoIRi).
Claims 81-86 of U.S. Application No. 19/093,051 are drawn to methods of treating or delaying progression of a disease, or stimulating an immune response or function, in an individual, comprising administering to said individual a therapeutically effective amount of an anti-CD3 bispecific molecule.
Claims 14 and 15 of U.S. Patent No. 10,253,104 are drawn to a method of treatment of a plasma cell disorder in a subject comprising administering an effective amount of a composition comprising a bispecific bi- or trivalent antibody specifically binding to two targets which are the extracellular domain of human B cell maturation antigen (BCMA) and human CD3ε (CD3) to said subject; and a method of treatment of Multiple Myeloma comprising administering an effective amount of a composition comprising a bispecific bi- or trivalent antibody specifically binding to two targets which are the extracellular domain of human B cell maturation antigen (BCMA) and human CD3ε (CD3) to said subject.
Claims 1-28 of U.S. Patent No. 12,195,547 are drawn to methods of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject glofitamab; and a method of treating a population of subjects having a relapsed and/or refractory NHL comprising administering to the subjects glofitamab.
Claims 167-205 of U.S. Patent No. 18/964,055 are drawn to methods of treating a subject having a CD20-positive cell proliferative disorder comprising administering to the subject glofitamab.
Claims 1-9 of U.S. Patent No. 12,565,530 are drawn to a method for treating cancer in a subject, wherein the method comprises administering to the subject an effective amount of a T-cell activating anti-carcinoembryonic antigen (CEA)/anti-CD3 bispecific antibody.
Claims 42, 46, and 47 of U.S. Application No. 18/069,847 are drawn to a method of treating an epithelial cancer in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule; a method of treating a squamous cell carcinoma in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule; and a method of treating cancer in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule.
Claims 1-5 of U.S. Patent No. 9,963,513 are drawn to a method of treating multiple myeloma (MM) comprising administering a bispecific antibody specifically binding to human B cell maturation factor (BCMA) and CD3 to a subject in need thereof.
Claims 50 and 51 of U.S. Application No. 18/066,529 are drawn to a of treating a disease in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising the protease-activatable anti-CD3 T cell activating bispecific molecule.
Claims 1-39 of U.S. Patent No. 10,781,258 are drawn to a method of treating a CEA-expressing cancer in an individual, the method comprising administering to the individual a therapeutically effective amount of a composition comprising an anti-CD3 T cell activating bispecific antigen-binding molecule in a pharmaceutically acceptable form; and a method for inducing lysis of a CEA-expressing tumor target cell, the method comprising contacting the CEA-expressing tumor target cell with an anti-CD3 T cell activating bispecific antigen-binding molecule comprising.
Claims 15 and 20 of U.S. Application No. 18/772,922 are drawn to a methods of treating cancer in a patient, the method comprising administering to the patient an effective amount of a multispecific antibody that binds to human HLA-G and to human CD3.
Claims 27-51 of U.S. Application No. 18/742,449 are drawn to a method of treating a MAGE-A4-expressing cancer in an individual, comprising administering to the individual an HLA-A2/MAGE-A4 x CD3 bispecific antibody.
Claims 27-51 of U.S. Application No. 18/646,492 are drawn to a method of treating a WT1-expressing cancer in an individual, comprising administering to the individual an HLA-A2/WT1 x CD3 bispecific antibody.
Claim 22 of U.S. Application No. 18/979,221 is drawn to a method of treatment comprising the administration of an anti-CD3 multimeric polypeptide to a patient in need of such treatment.
Claims 1-16 of U.S. Patent No. 11,672,858 are drawn to a method of treating a TYRP-1-expressing cancer in a human individual having a TYRP-1-expressing cancer, the method comprising administering to the individual an effective amount of an anti-CD3 bispecific antibody molecule.
Claims 1-19 of U.S. Application No. 19/136,536 are drawn to methods of treating a cancer in a patient, the method comprising administering a combination therapy comprising a CD47 blocking agent and an anti-CD20/ anti-CD3 bispecific antibody to the patient.
Claim 3 of U.S. Application No. 19/319,680 is drawn to a method of treating cancer in an individual comprising administering to said individual an anti- EGFRvill/anti-CD3 bispecific antibody in combination with a tumor-targeted 4-1BB agonist.
Claims 5, 7-14, 16, and 18-26 of U.S. Application No. 19/325,175 are drawn to a method for treating cancer in an individual comprising administering to the individual an effective amount of an anti-HLA-G/anti-CD3 bispecific antibody.
Claims 1, 7, 15, 16, 19, 28, 29, 33, 39, 42, 45, 47, 56, 58, 60, 63-65, 69, 89, 90, 93, 94, 97, 105, and 106 of U.S. Application No. 19/372,448 are drawn to methods for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in a human individual in need thereof, comprising administering to the human individual an effective amount of glofitamab.
The combined teachings of the claims of the above Patents and Applications in view of Khadka et al. and Zhang pertaining to claim 3, and the rationale for combining them are outlined in the NSDP rejection above.
The combined teachings do not teach that the NLRP3 inhibitor is specifically selnoflast.
The teachings of Schwaid and Spencer are outlined in the 103 rejection above.
It would be to one of ordinary skill in the art to modify the combined teachings the claims of the above Patents and Applications in view of Khadka et al. and Zhang as applied to claim 3, and incorporate the teachings of Schwaid and Spencer to include that the NLRP3 inhibitor is specifically selnoflast.
Given that somalix, also known as selnoflast, is a known peripherally restricted NLRP3 inhibitor; it would be obvious to a skilled artisan to specifically apply selnoflast as the NLRP3 inhibitor in the methods taught by the above Patents and Applications in view of Khadka et al. in view of Zhang with a reasonable expectation of success.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the above Patents and Applications would render the instant claims obvious.
This is a provisional nonstatutory double patenting rejection for the co-pending Applications because the patentably indistinct claims have not in fact been patented.
Claims 21-28 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of U.S. Patent No. 11,718,680 (the ‘680 Patent) in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592) , as applied to claims 3 and 18-20, and further in view of Hutchings et al. 2021 (J Clin Oncol 39, 1959-1970) as evidenced by Strohl 2024 (Antib Ther. 7(2):132–156).
The combined teachings of the claims of the ‘680 Patent in view of Khadka et al. and Zhang pertaining to claims 3 and 18-20, and the rationale for combining them are outlined in the NSDP rejection above.
The combined teachings do not teach that the anti-CD20/CD3 antibody is glofitamab. It is noted that glofitamab comprises all of the features recited in claims 21-27 and 36.
The teachings of Hutchings et al. and Strohl are outlined in the 103 rejection above.
It would be to one of ordinary skill in the art to modify the combined teachings the claims of the ‘680 Patent in view of Khadka et al. and Zhang as applied to claims 3 and 18-20, and incorporate the teachings of Hutchings et al. to include that that the T cell engager is glofitamab. This is because glofitamab has already proven successful in a methods of treating R/R B-NHL and DLBCL and because glofitamab can bivalently bind CD20 on B cells which leads to superior in vitro potency when compared to antibodies with monovalent binding to CD20 (Hutchings et al.).
It is noted and evidenced by the instant specification and Strohl that glofitamab is a trivalent, bispecific (“2:1”) IgG1κ/λ-based antibody with two combining sites targeting CD20 and one targeting CD3ε. The configuration of glofitamab, with proper cognate heavy/light chain pairing, is achieved by cross-over, chain-swapping technology combined with an asymmetric silenced Fc generated using a modified version of knobs-into-holes technology. Furthermore, glofitamab comprises glutamine residue substitutions at positions 147 and 213 of the CH1 domains of each of the CD20 antigen binding domains and an arginine residue substitution and a lysine residue substitution as positions 123 and 124 of the CL domains of each of the CD20 antigen binding domains. Therefore, glofitamab comprises all of the features recited in claims 21-28 and 36.
Given that glofitamab has been successfully applied in methods of treating R/R B-NHL and DLBCL, the CD20 bivalency of glofitamab endows the antibody with superior in vitro potency when compared to antibodies with monovalent binding to CD20, and glofitamab induces CRS which can be managed by moderate use of steroids or tocilizumab; it would be obvious to a skilled artisan to substitute CD20 bivalent glofitamab for the CD20 monovalent anti-CD20/CD3 antibody in the method for treating or delaying progression of a proliferative disease that expresses CD20 and CD19 in a subject taught by the ‘680 Patent in view of Khadka et al. in view of Zhang with a reasonable expectation of success. A skilled artisan would reasonably expect that the CD20 bivalency of glofitamab would be more potent than the monovalent anti-CD20/CD3 antibody taught by the ‘680 Patent.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘680 Patent would render the instant claims obvious.
Claims 21-28 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims in the following U.S. Patent and Applications in view of Khadka et al. 2019 (Immunotherapy. 11(10), 851–857) and Zhang 2021 (WO2021011592) , as applied to claims 3 and 18-20, and further in view of Hutchings et al. 2021 (J Clin Oncol 39, 1959-1970) as evidenced by Strohl 2024 (Antib Ther. 7(2):132–156) for similar reasons as the NSDP rejection to the ‘680 Patent above.
Claims 1-52 of U.S. Patent No. 10,596,257 are drawn to methods for treating or delaying progression of cancer in an individual comprising administering to the individual an effective amount of an anti-PD-L1 antagonist antibody and an anti-CEA/anti-CD3 bispecific antibody; and methods of enhancing immune function in an individual having cancer comprising administering an effective amount of an anti-PD-L1 antagonist antibody and an anti-CEA/anti-CD3 bispecific antibody.
Claims 1-28 of U.S. Patent No. 11,013,801 are drawn to a method of treating a carcinoembryonic antigen (CEA)-expressing cancer in a subject, the method comprising a treatment regimen comprising administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CEA; and a method of treating a CD20-positive B-cell disorder in a subject, the method comprising a treatment regimen comprising administering to the subject a therapeutic agent comprising a bispecific antibody, wherein the bispecific antibody specifically binds to CD3 and CD20.
Claim 26-28 and 30-32 of U.S. Application No. 18/347,362 is drawn to a method for treating a CD20 expressing cancer in a subject comprising administering to the subject an effective amount of an anti-CD20/anti-CD3 antibody and an effective amount of an anti-PD 1/anti-LAG3 bispecific antibody.
Claim 50, 51, 53, and 54 of U.S. Application No. 18/786,187 is drawn to a method of treating an individual who has a HER2-expressing cancer comprising administering to the individual a T-cell activating anti-CD3 bispecific antibody.
Claim 1-20 of U.S. Patent No. 10,781,262 is drawn to a method for treating or delaying progression of a cancer in an individual comprising administering to the individual an effective amount of an anti-CD3 T cell activating bispecific antigen-binding molecule and a PD-1 axis binding antagonist antibody; and a method of enhancing immune function in an individual having a FolR1-positive cancer comprising administering to the individual an effective amount of a combination of: (a) a T cell activating bispecific antigen-binding molecule specific for FolR1 and CD3.
Claim 25 of U.S. Application No. 18/493,659 is drawn to a method of treating a disease, in an individual, comprising administration of a T-cell activating agent, such as an antibody that binds to CD3.
Claims 10-12, 35, 36, 39, and 40 of U.S. Patent No. 12,098,213 are drawn to a method of treating an HLA-A2/WT1-expressing cancer in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising an anti-CD3 bispecific antigen binding molecule.
Claims 1-41 of U.S. Patent No. 12,629,419 are drawn to a method for preventing or mitigating an adverse effect related to the administration of a T cell bispecific antibody to an individual, comprising administering an anti-CD3 T cell bispecific antibody.
Claims 3, 6, 61-99, 107-114, 116-122, 126-127, 130, and 131 of U.S. Application No. 17/448,729 are drawn to a method for treatment of a cancer or an autoimmune disease in an individual, wherein said method comprises the administration of a T cell bispecific antibody to the individual, wherein the T cell bispecific antibody comprises an Fc domain composed of a first and a second subunit; and a method for preventing or mitigating an adverse effect related to the administration of a T cell bispecific antibody to an individual.
Claims 1 and 5-28 of U.S. Application No. 18/309,582 are drawn to methods of treating an individual having a cancer comprising administering to the individual an effective amount of a CEA CD3 bispecific antibody.
Claims 102-124 of U.S. Application No. 19/016,060 are drawn to a method of treating a subject having a relapsed or refractory (R/R) multiple myeloma (MM), the method comprising administering to the subject a bispecific antibody that binds to Fc receptor-homolog 5 (FcRH5) and cluster of differentiation 3 (CD3) and a method of treating a subject having a relapsed or refractory (R/R) multiple myeloma (MM), wherein the subject has previously received a B cell maturation factor (BCMA)-targeting therapeutic agent, the method comprising administering to the subject a bispecific antibody that binds to Fc receptor-homolog 5 (FcRH5) and cluster of differentiation 3 (CD3).
Claims 3-13 and 15-19 of U.S. Application No. 18/668,810 are drawn to a method of treating a tyrosinase-related protein 1 (TYRP1)- expressing cancer in an individual comprising administering to said individual a therapeutically effective amount of an anti-TYRP1/anti-CD3 bispecific antibody.
Claims 62, 63, and 64-66 of U.S. Application No. 18/421,912 are drawn to methods of treating a disease in an individual, comprising administering to the individual an effective amount of an antibody that binds to CD3 and Colony stimulating factor 1 receptor (CSF1R), comprising a first antigen binding domain that binds CD3 and a second antigen binding domain that binds to CSF1R.
Claims 23-35 of U.S. Application No. 19/310,373 are drawn to a method for treating an HLA-G expressing cancer in a subject comprising administering to the subject an effective amount of an anti-HLA-G/anti-CD3 antibody and an effective amount of an anti-PD1/anti-LAG3 bispecific antibody.
Claim 5 of U.S. Patent No. 12,065, 502 are drawn to a method of treatment, comprising administering to a subject who has cancer a pharmaceutical formulation comprising: 20 to 50 mg/ml of a CEA CD3 bispecific antibody.
Claims 29 and 34 of U.S. Application No. 18/063,459 are drawn to a method of treating a cancer in an individual, comprising administering to said individual an effective amount of an antibody that binds to CD3 and PLAP; and a method of treating an autoimmune disease in an individual, comprising administering to said individual an effective amount of an antibody that binds to CD3 and PLAP.
Claims 31-33, 45, and 61-64 of U.S. Application No. 18/066,526 are drawn to methods of treating a cancer in an individual comprising administering to the subject a bispecific antibody that binds to CD3 and Folate receptor 1 (FoIRi).
Claims 81-86 of U.S. Application No. 19/093,051 are drawn to methods of treating or delaying progression of a disease, or stimulating an immune response or function, in an individual, comprising administering to said individual a therapeutically effective amount of an anti-CD3 bispecific molecule.
Claims 14 and 15 of U.S. Patent No. 10,253,104 are drawn to a method of treatment of a plasma cell disorder in a subject comprising administering an effective amount of a composition comprising a bispecific bi- or trivalent antibody specifically binding to two targets which are the extracellular domain of human B cell maturation antigen (BCMA) and human CD3ε (CD3) to said subject; and a method of treatment of Multiple Myeloma comprising administering an effective amount of a composition comprising a bispecific bi- or trivalent antibody specifically binding to two targets which are the extracellular domain of human B cell maturation antigen (BCMA) and human CD3ε (CD3) to said subject.
Claims 1-9 of U.S. Patent No. 12,565,530 are drawn to a method for treating cancer in a subject, wherein the method comprises administering to the subject an effective amount of a T-cell activating anti-carcinoembryonic antigen (CEA)/anti-CD3 bispecific antibody.
Claims 42, 46, and 47 of U.S. Application No. 18/069,847 are drawn to a method of treating an epithelial cancer in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule; a method of treating a squamous cell carcinoma in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule; and a method of treating cancer in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of a composition comprising the bispecific agonistic CD/CD28 antigen binding molecule.
Claims 1-5 of U.S. Patent No. 9,963,513 are drawn to a method of treating multiple myeloma (MM) comprising administering a bispecific antibody specifically binding to human B cell maturation factor (BCMA) and CD3 to a subject in need thereof.
Claims 50 and 51 of U.S. Application No. 18/066,529 are drawn to a method of treating a disease in an individual, comprising administering to said individual a therapeutically effective amount of a composition comprising the protease-activatable anti-CD3 T cell activating bispecific molecule.
Claims 1-39 of U.S. Patent No. 10,781,258 are drawn to a method of treating a CEA-expressing cancer in an individual, the method comprising administering to the individual a therapeutically effective amount of a composition comprising an anti-CD3 T cell activating bispecific antigen-binding molecule in a pharmaceutically acceptable form; and a method for inducing lysis of a CEA-expressing tumor target cell, the method comprising contacting the CEA-expressing tumor target cell with an anti-CD3 T cell activating bispecific antigen-binding molecule comprising.
Claims 15 and 20 of U.S. Application No. 18/772,922 are drawn to a methods of treating cancer in a patient, the method comprising administering to the patient an effective amount of a multispecific antibody that binds to human HLA-G and to human CD3.
Claims 27-51 of U.S. Application No. 18/742,449 are drawn to a method of treating a MAGE-A4-expressing cancer in an individual, comprising administering to the individual an HLA-A2/MAGE-A4 x CD3 bispecific antibody.
Claims 27-51 of U.S. Application No. 18/646,492 are drawn to a method of treating a WT1-expressing cancer in an individual, comprising administering to the individual an HLA-A2/WT1 x CD3 bispecific antibody.
Claim 22 of U.S. Application No. 18/979,221 is drawn to a method of treatment comprising the administration of an anti-CD3 multimeric polypeptide to a patient in need of such treatment.
Claims 1-16 of U.S. Patent No. 11,672,858 are drawn to a method of treating a TYRP-1-expressing cancer in a human individual having a TYRP-1-expressing cancer, the method comprising administering to the individual an effective amount of an anti-CD3 bispecific antibody molecule.
Claims 1-19 of U.S. Application No. 19/136,536 are drawn to methods of treating a cancer in a patient, the method comprising administering a combination therapy comprising a CD47 blocking agent and an anti-CD20/ anti-CD3 bispecific antibody to the patient.
Claim 3 of U.S. Application No. 19/319,680 is drawn to a method of treating cancer in an individual comprising administering to said individual an anti- EGFRvill/anti-CD3 bispecific antibody in combination with a tumor-targeted 4-1BB agonist.
Claims 5, 7-14, 16, and 18-26 of U.S. Application No. 19/325,175 are drawn to a method for treating cancer in an individual comprising administering to the individual an effective amount of an anti-HLA-G/anti-CD3 bispecific antibody.
The combined teachings of the claims of the above Patents and Applications in view of Khadka et al. and Zhang pertaining to claims 3 and 18-20, and the rationale for combining them are outlined in the NSDP rejection above.
The combined teachings do not teach that the anti-CD20/CD3 antibody is glofitamab. It is noted that glofitamab comprises all of the features recited in claims 21-27 and 36.
The teachings of Hutchings et al. and Strohl are outlined in the 103 rejection above.
It would be to one of ordinary skill in the art to modify the combined teachings the claims of the above Patents and Applications in view of Khadka et al. and Zhang as applied to claims 3 and 18-20, and incorporate the teachings of Hutchings et al. to include that that the T cell engager is glofitamab. This is because glofitamab has already proven successful in a methods of treating R/R B-NHL and DLBCL and because glofitamab can bivalently bind CD20 on B cells which leads to superior in vitro potency when compared to antibodies with monovalent binding to CD20 (Hutchings et al.).
It is noted and evidenced by the instant specification and Strohl that glofitamab is a trivalent, bispecific (“2:1”) IgG1κ/λ-based antibody with two combining sites targeting CD20 and one targeting CD3ε. The configuration of glofitamab, with proper cognate heavy/light chain pairing, is achieved by cross-over, chain-swapping technology combined with an asymmetric silenced Fc generated using a modified version of knobs-into-holes technology. Furthermore, glofitamab comprises glutamine residue substitutions at positions 147 and 213 of the CH1 domains of each of the CD20 antigen binding domains and an arginine residue substitution and a lysine residue substitution as positions 123 and 124 of the CL domains of each of the CD20 antigen binding domains. Therefore, glofitamab comprises all of the features recited in claims 21-28 and 36.
Given that glofitamab has been successfully applied in methods of treating R/R B-NHL and DLBCL, the CD20 bivalency of glofitamab endows the antibody with superior in vitro potency when compared to antibodies with monovalent binding to CD20, and glofitamab induces CRS which can be managed by moderate use of steroids or tocilizumab; it would be obvious to a skilled artisan to substitute CD20 bivalent glofitamab for the monovalent anti-target cell antigen/CD3 antibody in the methods taught by the above Patents and Applications in view of Khadka et al. in view of Zhang with a reasonable expectation of success. A skilled artisan would reasonably expect that the target cell antigen bivalency of glofitamab would be more potent than the monovalent anti-target cell antigen/CD3 antibody taught by the above Patents and Applications.
Combining prior art elements according to known methods to yield predictable results is obvious to one of ordinary skill in the art (see MPEP § 2143(A)). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Therefore, the claims in the ‘680 Patent would render the instant claims obvious.
Conclusion
No claim is allowed.
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/GRACE H LUNDE/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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