DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Applicant’s preliminary amendments received 21NOV2024 are acknowledged.
Claims 1-138 have been canceled.
Claims 139-158 are new.
Claims 139-158 are pending in the instant application (i.e., Claim 139 is independent).
Priority
The present application is a continuation of 16/980771 filed 14SEP2020 (now abandoned) which is a 371 National Stage of PCT International Application No. PCT/US2019/022284, filed 14MAR2019, which claims the benefit of US Provisional Patent Application No. 62/642689, filed 14MAR2018. Applicant’s claim for the benefit of prior-filed application is acknowledged.
Information Disclosure Statement
The listing of references in the specification (e.g., p 67) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 139 is objected to because of the following informalities:
Claim 139 contains a typographical error: The “a” should be removed between “…binds” and “to G6B;….” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 140-144, 149, 153-154, and 157 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 140-144 drawn to the multispecific molecule comprising a first TTM that binds G6B and a second TTM that binds to CD34, wherein the first TTM comprises the HCDRs 1-3 and the LCDRs 1-3 of SEQ ID NOs: 87-89 and 90-92, respectively (i.e., claim 140) or wherein the first TTM comprises a VH and/or VL of SEQ ID NOs: 1 and/or 2, respectively (i.e., claims 141-144) are indefinite because the sequences are directed to the second TTM that binds CD34, rather than the first TTM that binds G6B. Correcting “first” to “second” would obviate this rejection.
Claims 149 and 157 appear to recite a Markush group, but the group of alternatives are not closed as required by a proper Markush group in MPEP §2173.05(h). In this instance, claims 149 and 157 recite Markush-type claims without reciting proper Markush-type language such as “selected from the group consisting of” and an “and” between the last two species. For example, in claim 149, “the group consisting of” is missing prior to listing the positions and in claim 157, an “and” should replace the ‘or’ between “…(PV),” and “chronic....”
Claims 153 and 154 recite the limitation "the composition of claim 139" however, claim 139 recites a multispecific molecule. Therefore, there is insufficient antecedent basis for this limitation in the claim. Examiner notes that changing “…the composition of claim 139…” to “…the multispecific molecule of claim 139…” in claim 153 and then changing the dependency of claim 154 to the pharmaceutical composition of claim 153 would obviate this rejection.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 139-158 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 and having support for:
“A multispecific molecule comprising:
a first tumor-targeting moiety (TTM) that binds to G6B; and
a second tumor-targeting moiety (TTM) that binds to CD34;
wherein the first TTM comprises the HCDR1-3 and the LCDR1-3 amino acid sequences of SEQ ID NOs: AA-CC and XX-ZZ, respectively (which in this instance are lacking in the specification) and
wherein the second TTM comprises the HCDR1-3 and the LCDR1-3 amino acid sequences of SEQ ID NOs: 87-89 and 90-91, respectively” (claims 139 and 140);
-AND-
“A multispecific molecule comprising:
a first TTM that binds to G6B; and
a second TTM that binds to CD34;
wherein the first TTM comprises a VH comprising HCDRs1-3 having the amino acid sequence of SEQ ID NO: XX and a VL comprising LCDRs1-3, having the amino acid sequence of SEQ ID NO: YY (which in this instance are lacking in the specification) and
wherein the second TTM comprises a VH comprising HCDRs1-3 having the amino acid sequence of SEQ ID NO: 1 and a VL comprising LCDRs1-3, having the amino acid sequence of SEQ ID NO: 2.” (claims 139 and 141-144);
-AND-
“A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the multispecific molecule comprising:
a first TTM that binds to G6B; and
a second TTM that binds to CD34;
wherein the first TTM comprises the HCDRs1-3 and the LCDRs1-3 amino acid sequences of SEQ ID NOs: AA-CC and XX-ZZ, respectively (which in this instance are lacking in the specification) and
wherein the second TTM comprises the HCDR1-3 and the LCDR1-3 amino acid sequences of SEQ ID NOs: 87-89 and 90-91, respectively.” (claims 139, 140, and 154);
does not reasonably provide enablement or support for more. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims nor does it provide sufficient description to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed had possession of the claimed invention. Claims 145-153 and 155-158 are also rejected since they are dependent on claim 139 but do not remedy the deficiencies.
In the instance of a bispecific antibody, it is well known in the art that such a construct comprises two pairs of VH/VL regions (i.e., one pair for each binding domain) and each VH/VL pair consists of six CDRs for a total of 12 CDRs (Brinkmann, et al., MABS, 2017, 9, 182-212, see p 183, col 1, ¶1 and Fig 1-2). 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, et al., Immunobiology: The Immune System in Health and Disease, 5th edition, 2001). It is also known that single amino acid changes in a CDR can abrogate the antigen binding function of an antibody (Rudikoff, et al., PNAS, 1982, 79, 1979-1983 see entire document, particularly the abstract and the middle of the left column of p 1982). 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. Furthermore, the pairing propensity of any two given germlines depends to a large extent on the sequence and conformation of HCDR3, which is highly variable and if HCDR3 is fixed, different VH/VL pairs can result in significant stability differences (Chiu, et al., Antibodies, 2019, 8, 1-80, Section 2.1.3). Therefore, the art supports that the nondegenerate CDR sequences for each antigen binding domain and the specific pairing of the VH and VL sequences for each antigen binding domain are necessary structural features to maintain functional binding.
Artisans are well aware that knowledge of a given antigen (for instance a specific epitope of G6B or CD34) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. 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 (Edwards, et al., J Mol Biol, 2003, 334, 103-118, see entire document). Goel et al. disclose the synthesis of three monoclonal antibodies that bind to the same short (12-mer) peptide and found that the sequences of these antibodies which bound the same epitope exhibited diverse V gene usage indicating their independent germline origin (Goel, et al., J Immunol, 2004, 173, 7358-7367, see entire document). Further, it should be noted that degenerate binding of the same structural motif by antibodies does not require the existence of sequence homology or identity at any of their CDRs or other chemical similarities at the antigen-binding sites; side chain mobility of epitope residues can confer steric and electrostatic complementarity to differently shaped combining sites, allowing functional mimicry to occur (Lescar et al., J Biol Chem, 1995, 270, 18067-18076, see entire document, in particular Abstract and Discussion). 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 represent the breadth of the genus of antibodies that bind the given antigen in the instant application.
With regards to claim 145, which recites that the multispecific molecule “comprises a full-length antibody,…or a camelid antibody” it is known in the art that in the instance of single domain antibodies, the formation of an intact antigen-binding site requires the association of three CDRs for VHH antibodies (rather than the six present in conventional VH/VL antibodies (Henry, et al., MAbs, 2018, 10, 815-826, see entire document). Furthermore, Gordon teaches that the CDR3 loop contributes most to sdAb-antigen binding specificity and is typically longer than the CDR-H3 loop of a conventional antibody (Gordon, et al., Front Immunol, 2023, 14, 1-18, see entire document). Asaadi, et al., teach that the sdAbs evolved with an extra disulfide bond between CDR1, CDR2, or FR2, which in addition to the other structural features of a sdAb increases paratope diversity and allows for a wide variety of geometrical loop structures that deviate fundamentally from the canonical loop structures defined for conventional antibodies (Asaadi, et al., Biomarker Res, 2021, 9, 1-20, see entire document). Therefore, the specific combination of CDRs 1-3 affects structure within the sdAb and specific antigen binding. Thus, based upon the prior art, skilled artisans would reasonably understand that it is the organization of the three CDRs in a specific combination, in a single domain antibody, which gives rise to the functional property of antigen binding to in this instance, G6B or CD34.
For example, below is an alignment of five HCDR3 sequences of an anti-G6B antibodies disclosed in US 2025/0011459 A1 (Loew, et al., 09JAN2025). Despite sharing the same immunogen (G6B) the resulting antibodies share little similarity at the sequence level:
Amino acid sequence
1
Y
A
Q
L
G
L
Y
A
Y
F
D
V
2
N
D
W
D
Y
F
D
Y
3
E
R
N
Y
G
I
Y
D
I
D
H
4
R
L
Y
S
G
S
Y
Y
F
D
F
5
R
H
W
D
A
F
D
Y
It is noted that applicant has also claimed a method of administering a product. However, artisans must reasonably be in possession of a product in order to be in possession of methods of administering said product. As has been discussed above, the broadest claims describe the administered product based upon what it does, such as targeting G6B and CD34. However, as has been made clear by recent court cases as well as USPTO guidance, describing an antibody simply by what it binds is not sufficient to provide adequate written description for the recited genus, and has been mentioned while antibodies are members of the genus of targeting moiety it is not limited thereto. Indeed, as taught by Edwards et al., Lescar et al., and Goel et al., the number of potential antibody structures (i.e., sequences) which can bind to the same antigen is literally astronomical, and when it is considered that the agent doing the “binding” can literally be anything including a small molecule, lipid, peptide, protein, polysaccharide, nucleotide, etc., the size of the genus of administered reagents grows. As such, describing the administered reagent based upon what it binds, where it binds, or its function as an inhibitor fails to necessarily provide a structure that gives rise to the aforementioned properties.
The specification discloses exemplary multifunctional constructs (Fig 1-2) comprising a first TTM, second TTM, third TTM, immune cell engager, cytokine, and/or stromal modifying moiety. Examples of TTM are provided; however, there is no clear structural definition of what a TTM encompasses (i.e., antibody or fragment thereof, peptide, polysaccharide, etc.). Furthermore, while there are exemplary structures of the CD34 TTM in Tables 2-4; there are no examples of G6B TTM. Therefore, claims 139-158 as presently claimed are rejected because the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims nor does it provide sufficient description to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed had possession of the claimed invention.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 139 and 152 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent No. 9364498 B2 (Hossainy, et al., 14JUN2016), herein referred to as “’498” as evidenced by de Vet, et al., (FEBS Lett, 2005, 579, 2355-2358), herein referred to as “de Vet.”
‘498 teaches heparin-based conjugates comprising a modified heparin (i.e., a stromal modifying moiety), which as evidenced by de Vet, heparin binds to the cell surface receptor G6b (see abstract) and an anti-CD34 antibody (col 7, lines 24-26).
Therefore, the prior art anticipates the invention as presently claimed.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 141-148 and 153-154 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 9364498 B2 (Hossainy, et al., 14JUN2016), herein referred to as “’498” as evidenced by de Vet, et al., (FEBS Lett, 2005, 579, 2355-2358), herein referred to as “de Vet” as applied to claims 139 and 152 and in further view of U.S. Patent No. 8399249 B2 (Kerschbaumer, et al., 19MAR2013), herein referred to as “’249” and Lazo-Langer, et al., (J Thromb and Haem, 2007, 5, 729-737), herein referred to as “Lazo.”
The teachings of ‘498 as evidenced by de Vet are summarized above.
However, they do not teach: wherein the [second] TTM comprises a VH and VL of SEQ ID NOs: 1 and 2; or wherein the multispecific molecule comprises a full-length antibody; or wherein the multispecific molecule comprises an IgG1 Fc region; or a pharmaceutical composition thereof; or a method of treating cancer comprising administering a multispecific molecule targeting G6b and CD34.
Nevertheless, ‘249 teaches generation of recombinant anti-CD34 antibodies comprising the HC and the LC of SEQ ID NOs: 2 and 4 (i.e., 100% query match to SEQ ID NOs: 1 and 2 of the instant application, see OA.APPENDIX), wherein the HC comprises a mouse IgG1 Fc region (col 3, lines 33-37 and lines 49-54, col 4, lines 25-27, col 6, lines 26-31, and Example 1). Furthermore, ‘249 teaches that CD34 is mainly expressed on early lymphohematopoietic stem and progenitor cells as well as small-vessel endothelial cells and that anti-CD34 antibodies can be used to select CD34+ peripheral blood stem cells for use in stem cell transplants after high dose chemotherapy, autologous transplantation studies and tumor cell purging (col 3, lines 43-47 and 49-54).
Furthermore, Lazo teaches that low-molecular-weight heparins have an antitumor effect in vitro and in experimental animal models of malignancy (see entire document, specifically see summary). Lazo further teaches that heparins likely have a positive impact on patient survival due to multiple mechanisms involving inhibition of the proliferation of malignant cell types, blockage of angiogenesis by decreasing the activity of proangiogenic factors, activation of NK cells, and blockage of the metastatic process (¶2 of Background section).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the multifunctional heparin anti-CD34 conjugate disclosed by ‘498 by utilizing a specific anti-CD34 antibody for anti-cancer therapy disclosed by ‘249 and Lazo because the high yielding and specific anti-CD34 antibody combined with a G6b targeting heparin is useful in a variety of clinical scenarios such as cancer therapy. One would have been motivated to do so, given the teachings of ‘498 that the G6b targeting heparin could be conjugated to an anti-CD34 antibody. There would have been a reasonable expectation of success, given the knowledge that the combination of the anti-CD34-heparin conjugate as taught by ‘498 would result in utilizing a specific anti-CD34 antibody which can be readily generated at high yields for targeting CD34 on vascular endothelial cells (i.e., angiogenesis for example in tumor vasculature) and a heparin conjugate for targeting G6b and delivering the anti-angiogenic properties of heparin as taught by ‘249 and Lazo.
Thus, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time of filing.
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 139 and 145-158 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 148-175 of co-pending Application No. 18/779692; herein referred to as the “reference application.” Although the claims at issue are not identical, they are not patentably distinct from each other because the multispecific molecule and methods of use of the reference application anticipates the multispecific molecule and methods of use of the instant application. Specifically, the molecule of claim 153 of the reference application comprising a first and second antigen binding moiety of CD34 and G6b of the reference application and the method of treating cancer of claim 170, wherein a therapeutically effective amount of the multispecific molecule comprising a first antigen binding moiety of CD34 is administered to a subject having cancer each anticipate the product and method of the instant application.
Co-pending claims of the reference application:
Instant Application patent claims, underline corresponds to direct mapping to claim 148 of the reference application and italics corresponds to the additional claim limitations.
148. A composition comprising a multispecific molecule or a recombinant nucleic acid encoding the multispecific molecule, wherein the multispecific molecule comprises a first antigen binding moiety, wherein the first antigen binding moiety comprises an anti-CD34 antibody or an anti-CD34 antigen binding fragment, wherein the anti-CD34 antibody or the anti-CD34 antigen binding fragment comprises: (i) a heavy chain variable domain (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) of SEQ ID NO: 280, a heavy chain complementarity determining region 2 (HC CDR2) of SEQ ID NO: 281, and a heavy chain complementarity determining region 3 (HC CDR3) of SEQ ID NO: 282; and (ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) of SEQ ID NO: 289, a light chain complementarity determining region 2 (LC CDR2) of SEQ ID NO: 290, and a light chain complementarity determining region 3 (LC CDR3) of SEQ ID NO: 291.
153. The composition of claim 148, wherein the multispecific molecule further comprises a second antigen binding moiety, wherein the second antigen binding moiety comprises an anti-G6B antibody or an anti-G6B antigen binding fragment.
160. The composition of claim 153, wherein the anti-G6B antibody or the anti-G6B antigen binding fragment comprises a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv (scFv), a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, a bispecific antibody, or a camelid antibody.
161. The composition of claim 148, wherein the multispecific molecule comprises at least two non-contiguous polypeptide chains comprising a first polypeptide and a second polypeptide chain, wherein the first polypeptide comprises a first member of a dimerization module and the second polypeptide comprises a second member of the dimerization module, wherein the first polypeptide and the second polypeptide form a complex via the first member of the dimerization module and the second member of the dimerization module, and wherein the first member of the dimerization module comprises a first heavy chain constant region and the second member of the dimerization module comprises a second heavy chain constant region.
162. The composition of claim 161, wherein the first heavy chain constant region comprises a first Fc region, and the second heavy chain constant region comprises a second Fc region.
163. The composition of claim 162, wherein the first Fc region comprises an amino acid sequence with at least 70% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 302-307 and 310-313 and/or the second Fc region comprise an amino acid sequence with at least 70% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 302-307 and 310-313.
165. The composition of claim 153, wherein the first antigen binding moiety, the second binding moiety, or a combination thereof comprises a light chain constant region selected from the group consisting of a human kappa light chain constant region and a human lambda light chain constant region.
168. The composition of claim 148, wherein the multispecific molecule further comprises an immune cell engager, a cytokine molecule, a modulator of a cytokine molecule, a stromal modifying moiety, or any combination thereof, and wherein the immune cell engager is selected from the group consisting of a T cell engager, an NK cell engager, a B cell engager, a dendritic cell engager, and a macrophage cell engager.
169. A pharmaceutical composition comprising the composition of claim 148, and a pharmaceutically acceptable carrier, excipient, or stabilizer.
170. A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the composition of claim 148, wherein the administering is effective to treat the cancer in the subject.
171. The method of claim 170, wherein the cancer is a solid cancer, a hematological cancer, or a myeloproliferative neoplasm.
173. The method of claim 170, wherein the cancer is a myeloproliferative neoplasm selected from the group consisting of primary or idiopathic myelofibrosis (MF), essential thrombocythemia or thrombocytosis (ET), polycythemia vera (PV), chronic myelogenous leukemia (CML), and myelofibrosis.
139. A multispecific molecule, comprising:(a) a first tumor-targeting moiety that binds a to G6B; and (b) a second tumor-targeting moiety that binds to CD34.
145. The multispecific molecule of claim 139, wherein the multispecific molecule comprises a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv (scFv), a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, a bispecific antibody, or a camelid antibody.
146. The multispecific molecule of claim 139, wherein the multispecific molecule comprises at least two non-contiguous polypeptide chains comprising a first polypeptide and a second polypeptide chain, wherein the first polypeptide comprises a first member of a dimerization module and the second polypeptide comprises a second member of the dimerization module, wherein the first polypeptide and the second polypeptide form a complex via the first member of the dimerization module and the second member of the dimerization module, and wherein the first member of the dimerization module comprises a first heavy chain constant region and the second member of the dimerization module comprises a second heavy chain constant region.
147. The multispecific molecule of claim 146, wherein the heavy chain constant region is selected from the group consisting of IgG1 or fragment thereof, IgG2 or fragment thereof, IgG3 or fragment thereof, and IgG4 or fragment thereof (i.e., of SEQ ID NOs: 302-307 and 310-313 of the reference application).
148. The multispecific molecule of claim 146, wherein the first heavy chain constant region comprises a first Fc region, and the second heavy chain constant region comprises a second Fc region.
149. The multispecific molecule of claim 148, wherein the first Fc region or the second Fc region comprise an amino acid substitution at a position selected from one or more of 347, 349, 350, 351, 366, 368, 370, 392, 394, 395, 397, 398, 399, 405, 407, and 409 of the Fc region of human IgG1 (i.e., SEQ ID NOs: 310 and 311 of the reference application).
150. The multispecific molecule of claim 148, wherein first Fe region comprises an amino acid substitution selected from the group consisting of T366S, L368A, andY407V and the second Fe region comprises an amino acid substitution of T366W, or the first Fe region comprises an amino acid substitution of T366W and the second Fe region comprises an amino acid substitution selected from the group consisting of T366S,L368A, and Y407V (i.e., SEQ ID NOs: 310 and 311 of the reference application).
151. The multispecific molecule of claim 139, wherein the first tumor-targeting moiety, the second tumor-targeting moiety, or a combination thereof comprises a light chain constant region selected from the group consisting of a human kappa light chain constant region and a human lambda light chain constant region.
152. The multispecific molecule of claim 139, wherein the first tumor-targeting moiety, the second tumor-targeting moiety, or a combination thereof comprises a light chain constant region selected from the group consisting of a human kappa light chain constant region and a human lambda light chain constant region.
153. A pharmaceutical composition comprising the composition of claim 139 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
154. A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the composition of claim 139, wherein the administering is effective to treat the cancer in the subject.
155. The method of claim 154, wherein the cancer is a solid tumor cancer or a hematological cancer.
156. The method of claim 155, wherein the cancer is the hematological cancer and wherein the cancer is a myeloproliferative neoplasm.
157. The method of claim 156, wherein the myeloproliferative neoplasm is selected from a group consisting of primary or idiopathic myelofibrosis (MF), essential thrombocytosis (ET), polycythemia vera (PV), or chronic myelogenous leukemia (CML).
158. The method of claim 156, wherein the cancer is myelofibrosis.
In this instance, because certain claims of the reference application are silent on the G6B targeting moiety of the instant claims, the specification was consulted to determine the scope of the generic term of composition. Per the specification of the reference application, the composition comprising a multifunctional molecule, wherein the multifunctional molecule comprises an anti-CD34 antibody linked to an antigen binding moiety, wherein the antigen binding moiety is an anti-G6B antibody and wherein the multifunctional molecule of the composition further comprises the Fc or immune cell engager (¶0049-0050, 0081-0084, 0087, and 0097).
Therefore, because the product of claim 153 of the reference application fully anticipates the product of claim 139 of the instant application and because dependent claims of the reference application use open language regarding the composition of the multispecific molecule comprising the CD34 targeting moiety (i.e., claim 148 of the reference application) which encompasses a second anti-G6b targeting moiety, there is no clear difference in the scope between the products and methods of the instant and reference applications.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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