DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 09/12/2024, is acknowledged.
3. Claims 1-4, 6, 8, 10, 12, 14-21, 25-27, 30 and 35 are pending.
4. Applicant’s IDS, filed 03/20/2024, is acknowledged.
5. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
6. Claims 1-4, 6, 8, 10, 12, 14-21, 25-27, 30 and 35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims encompass a broad genus of monoclonal anti-Siglec-5 antibodies that inhibit the interaction between Siglec-5 and the Siglec-5 ligand, treat cancers, increases production of at least one pro-inflammatory cytokine by at least 1.5-fold, at least 2-fold, at least 2.5-fold or at least 3-fold in a co-culture of (i) engineered human T cells transduced with a TCR (1383i) and (ii) MEL624 cells relative to the absence of the antibody or ligand-binding portion thereof, wherein the one or more pro-inflammatory cytokines comprises IFNγ, treat breast cancer, cervical cancer, ovarian cancer, colon cancer, colorectal cancer, rectal cancer, renal cancer, urothelial cancer, bladder cancer, prostate cancer, pancreatic cancer, intestinal cancer, anal cancer, head and neck cancer, pharynx cancer, gastro-esophageal cancer, esophageal cancer, nasopharyngeal cancer, thyroid cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, T-cell lymphoma, T cell leukemia, B cell leukemia, a myeloid leukemia, a lymphoid leukemia, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), myeloid leukemia, Hairy cell leukemia, promyelocytic leukemia (PML), myelodysplastic syndrome (MDS), a- lymphoproliferative disease, liver cancer, central nervous system cancer, skin cancer, and mesothelioma, (a) binds to human Siglec-5 with a kD of [1 x 10-7 M] or less (b) does not substantially reduce cell surface levels of Siglec-5 expressed on an immune cell (e.g. activated T cell) in vitro and/or in vivo (c) increases T-cell proliferation in a Mixed Lymphocyte Reaction (MLR) assay (d) increases IL-2 secretion in a MLR assay (e) increases T-cell proliferation and/or increases IL-2 secretion in a T cell proliferation assay (f) binds to human Siglec-5 and cynomolgus monkey Siglec-5 (g) inhibits binding of Siglec-5 to a Siglec-5 ligand expressed on an immune cell (h) inhibits tumor cell growth in vivo (i) does not cross-react with human Siglec-14.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of inhibit the interaction between Siglec-5 and the Siglec-5 ligand, treat cancers, increases production of at least one pro-inflammatory cytokine by at least 1.5-fold, at least 2-fold, at least 2.5-fold or at least 3-fold in a co-culture of (i) engineered human T cells transduced with a TCR (1383i) and (ii) MEL624 cells relative to the absence of the antibody or ligand-binding portion thereof, wherein the one or more pro-inflammatory cytokines comprises IFNγ, treat breast cancer, cervical cancer, ovarian cancer, colon cancer, colorectal cancer, rectal cancer, renal cancer, urothelial cancer, bladder cancer, prostate cancer, pancreatic cancer, intestinal cancer, anal cancer, head and neck cancer, pharynx cancer, gastro-esophageal cancer, esophageal cancer, nasopharyngeal cancer, thyroid cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, T-cell lymphoma, T cell leukemia, B cell leukemia, a myeloid leukemia, a lymphoid leukemia, acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), acute promyelocytic leukemia (APML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), myeloid leukemia, Hairy cell leukemia, promyelocytic leukemia (PML), myelodysplastic syndrome (MDS), a- lymphoproliferative disease, liver cancer, central nervous system cancer, skin cancer, and mesothelioma, (a) binds to human Siglec-5 with a kD of [1 x 10-7 M] or less (b) does not substantially reduce cell surface levels of Siglec-5 expressed on an immune cell (e.g. activated T cell) in vitro and/or in vivo (c) increases T-cell proliferation in a Mixed Lymphocyte Reaction (MLR) assay (d) increases IL-2 secretion in a MLR assay (e) increases T-cell proliferation and/or increases IL-2 secretion in a T cell proliferation assay (f) binds to human Siglec-5 and cynomolgus monkey Siglec-5 (g) inhibits binding of Siglec-5 to a Siglec-5 ligand expressed on an immune cell (h) inhibits tumor cell growth in vivo (i) does not cross-react with human Siglec-14. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, 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.
The specification at [0163] disclosed Five 30-to 50-day old female BALB/c mice were injected intraperitoneally on days 0, 14, 21, 28, 35,42, 43, and 44 with a human Siglec-5 antigen (Cat #SI5-H5250 ACROBiosystems Inc.) or a soluble Siglec-5 generated internally, the antigen was mixed in alum adjuvant at 100 micrograms of protein antigen per mouse (total volume 100 micrograms/microliter per mouse).
[0170] Monoclonal antibodies (mAbs) against Siglec-5 (generated in Example 1) were tested to determine if they recognize cell surface human Siglec-5 and whether they modulate a T cell antigen response.
[0171] Tissue culture supernatants from the 1920 hybridomas were screened by ELISA against Siglec-5 (Cat #SIS-H5250 ACROBiosystems Inc.) and probed with an HRP-labeled Goat Anti-Mouse IgG secondary antibody. TMB (T5569-100 ml) was used in the reaction to visualize positives. H2SO4 or sulfuric acid was used to stop the reaction. Positive hybridoma clones >0.3 OD in this assay continued to the next level of development, and were subcloned.
The specification discloses that [0179] antibodies that were positive for binding to human Siglec-5 were tested for their ability to bind activated T-cells and their ability to expand or grow out activated T-cell populations or to contract or decrease the growth of activated T-cell populations. The data in FIG. 2 show the percent difference in live cell count after 4 days of stimulation in the presence of anti-Siglec5 Abs compared with mouse IgG control. Two clones showed more than a 10% increase in live cell count compared to the IgG control. Three other clones showed a mild increase. Five clones showed more than 10% reductions in cell count. In the first set of twenty monoclonal antibody clones, two clones (clone #5, #6) promoted activated T-cell growth by acting on the Siglec-5 present on both CD4 and CD8 positive activated T-cells. (FIG. 2).
Besides monoclonal anti-Siglec-5 antibodies #5 and #6, no other antibodies that specifically bind Siglec-5 and inhibits an interaction between an immune cell that expresses Siglec-5 and a cancer cell that expresses a Siglec-5 ligand is disclose.
Claim 1 requires a monoclonal antibody against Siglec-5 that " inhibits the interaction between Siglec-5 and the Siglec-5 ligand” recited in claim 1. While the amino acid sequence of Siglec-5, SEQ ID NO: 1 with 557 amino acid long was known, immunizing an animal with Siglec-5 will generate antibodies directed to a number of different epitopes within the amino acid residues at positions 557 of SEQ ID NO: 1 and not necessarily to the same epitope which inhibits the interaction between Siglec-5 and the Siglec-5 ligand. The knowledge of the amino acid sequence of Siglec-5, by itself, did not put Applicants in possession of antibodies that inhibits the interaction between Siglec-5 and the Siglec-5 ligand, inhibits interaction between Siglec-5 expressed on an activated T cell and a Siglec-5 ligand expressed- on the cancer cell, increases production of at least one pro-inflammatory cytokine by at least 1.5-fold, at least 2-fold, at least 2.5-fold or at least 3-fold in a co-culture of (i) engineered human T cells transduced with a TCR (I383i) and (ii) MEL624 cells relative to the absence of the antibody or ligand-binding portion thereof, wherein the one or more pro-inflammatory cytokines comprises IFNγ.
When a claim contains functional language but the specification lacks any teaching regarding the amino acid residues that are critical for the function, there is a lack of written description because the function language limits the claim to a subset of species, and those skilled in the art would not know which species are in the subset and which species aren't. In other words, absent any teaching of structure-function relationships, the skilled in the art cannot determine the critical antigen/epitope that in the recited sequence and also possess the recited function. See AbbVie Deutschland GmbH v. Janssen Biotech, Inc. (Fed. Cir. 2014).
The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence, see MPEP 2163. Here, with respect to making monoclonal anti-Siglec-5 antibody which inhibits the interaction between Siglec-5 and the Siglec-5 ligand, the unpredictability is best demonstrated by the recent court decision in AbbVie v. Janssen Biotech and Centocor Biologics (Fed. Cir. 2014), the court found that AbbVie's generic claim can be classified as a set of human antibodies defined functionally by their high affinity and neutralizing activity to the human IL-12 antigen. However, AbbVie did not disclose any structural features common to the members of the genus. Rather, AbbVie's patent described only one type of structurally similar antibodies rather than antibodies representative of the full scope of the genus.
Absent any teaching of structure-function relationships, the skilled in the art cannot determine the critical amino acids in the CDR in the recited sequence and also possess the recited function. See AbbVie Deutschland GmbH v. Janssen Biotech, Inc. (Fed. Cir. 2014).
The claims encompass a broad genus of anti-Siglec-5 antibody, However, the USPTO has released a Memo on the Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, 02/22/2018.
See https://www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf.
The Memo clarifies the applicability of USPTO guidance regarding the written description requirement of 35 U.S.C. § 112(a) concerning the written description requirement for claims drawn to antibodies, including the following.
“In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional”.
In contrast to applicant’s reliance of describe the epitope of the Siglec-5 in providing a fully characterized antigen / specific epitope as well as claiming structural elements of the antigen, one or more functions recited in the claims and binding affinity, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-Siglec-5 antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017).
There is no evidence that knowledge of the chemical structure of an antigen gives the required kind of structure identifying information about the corresponding antibodies Applicants attempt to describe the invention by describing something that is not the invention: viz., the antigens to which the antibodies may bind. There nothing in the disclosure that describes the antibodies as required by the test set forth in Ariad.
However, the anti-Siglec-5 antibodies are required to practice the invention. The specification also fails to provide any specific structural or physical information so as to define a genus of antibodies having the desired therapeutic properties. Applicant is merely relying on the identification of Siglec-5 as the antigen and the well-known structure of antibodies in general. However, the claims do not recite a general antibody, but an antibody having a specific desired activity. However, Federal Circuit clarification of the law of written description as it applies to antibodies. Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017).
The claims are directed to a genus of anti-Siglec-5 antibodies. However, Federal Circuit clarification of the law of written description as it applies to antibodies. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed anti-Siglec-5 antibodies to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e. the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
For instance, citing to Centocor, the Court analogized an antigen and antibody to a lock and a key. For an antigen where there is only a finite number of binding antibodies, discovering those antibodies may be routine and conventional, and description of the antigen alone may be sufficient. By contrast, for antigens with millions of keys, or millions of potentially binding antibodies, description of the antigen and even a couple of examples may be far from sufficient.
Artisans are well aware that knowledge of a given antigen (for instance Siglec-5) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al (J Mol Biol. 2003 Nov 14;334(1): 103-18) 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 FICDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document). Similarly, Lloyd et al (Protein Eng Des Sel. 2009 Mar;22(3):159-68) teach that a large majority of VH/VL germline gene segments are used in the antibody response to an antigen, even when the antibodies were selected by antigen binding, as their sequencing studies revealed that out of 841 unselected and 5,044 selected antibodies, all but one of the 49 functional VH gene segments was observed (see entire document). Goel et al (J Immunol. 2004 Dec 15; 173(12):7358-67) disclose the synthesis of three mAbs 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 (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 sequence bound 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. Indeed, Kanyavuz et al (Nat Rev Immunol. 2019 Jun; 19(6):355-368) teach that “Theoretically, under physiological conditions, the human immune system can generate BCRs with 1026 distinct sequences, an astronomical number that is far greater than the calculated number of all B cell clones that can be generated during the lifespan of a healthy human (estimated to be 4 x 1014).
Given the claimed broadly class of antibodies and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of monoclonal antibodies to Siglec-5, including the claimed functional characteristics set forth in the Claims, the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of monoclonal anti-Siglec-5 antibodies falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
The specification at best describes plan for making antibodies that bind monoclonal anti-Siglec-15 antibodies and then identifying those that satisfy claim limitations, but mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
"When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (fed. Cir. 2005)) (emphasis added).
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
7. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
8. Claims 1-4, 6, 8, 10, 12, 14-21, 25-27, 30 and 35 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by patent WO 2018213316 A1 / US Pat. 11/359014 (102(a)(2) /US Pat. 11965023 (102(a)(2).
The `316 publication teaches and claims several monoclonal anti-Siglec-5 antibodies, wherein the anti-Siglec-5 antibody binds to one or more amino acids within amino acid residues 17-441, 19-360, 19-330, 19-229, 19-136, 146-229, or 236-330 of SEQ ID NO: 1, wherein the anti-Siglec-5 antibody binds to one or more amino acids within amino acid residues 63-71, 83-92, and 125-132 of SEQ ID NO: 1, wherein the anti-Siglec-5 antibody competes with one or more antibodies selected from the group consisting of 2G5, 7A5, 8A1, 10B6, 10F9, 6G2, 8C3, 4D6, 7E7, 11C6, 11H3, 9A5, 5H2, 9B1, and any combination thereof for binding to Siglec-5, wherein the antibody further inhibits interaction between Siglec-5 and one or more Siglec-5 ligands (published claims 1-2), an isolated monoclonal anti-Siglec-5 antibody, wherein the anti-Siglec-5 antibody decreases cellular levels of Siglec-5 and inhibits interaction between Siglec-5 and one or more Siglec-5 ligands, wherein the anti-Siglec-5 antibody decreases cell surface levels of Siglec-5, decreases intracellular levels of Siglec-5, decreases total levels of Siglec-5, or any combination thereof, wherein the antibody decreases cellular levels of Siglec-5 in vivo, wherein the anti-Siglec-5 antibody inhibits cell surface clustering of Siglec-5, wherein the anti-Siglec-5 antibody induces neutrophil extracellular traps (NET) formation in neutrophils, wherein the anti-Siglec-5 antibody has dissociation constant (KD) for human Siglec-5 and mammalian Siglec-5 that ranges from about 10 nM to about10 pM, or less than 10 pM, wherein the KD is determined at a temperature of approximately 25ºC, wherein the anti-Siglec-5 antibody is a bispecific antibody recognizing a first antigen and a second antigen, wherein the first antigen is Siglec-5 and the second antigen is ligands and/or proteins expressed on immune cells, wherein the ligands and/or proteins selected from the group consisting of PD1/PDL1, CD40, OX40, ICOS, CD28, CD137/4- 1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD-1, B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD30, TIGIT, VISTA, KIR, GAL9, TIM1, TIM3, TIM4, A2AR, LAG3, DR-5, CD2, CD5, CD39, CD73, and phosphatidylserine (i.e., bispecific means co-administered/concurrently) (see published claims 1-69).
Regarding claim 2, the `316 teaches that the cellular levels of Siglec-5 are measured on primary cells selected from the group consisting of dendritic cells, bone marrow-derived dendritic cells, monocytes, microglia, macrophages, neutrophils, and NK cells, or on cell lines, and wherein the cellular levels of Siglec-5 are measured utilizing an in vitro cell assay.
The `316 publication teaches and claims methods of preventing, reducing risk, or treating a disease, disorder, or injury selected from the group consisting of dementia, frontotemporal dementia, Alzheimer’s disease, vascular dementia, mixed dementia, taupathy disease, infections, and cancer, comprising administering to an individual in need thereof a therapeutically effective amount of an agent that decreases cellular levels of Siglec-5, inhibits interaction between Siglec-5 and one or more Siglec-5 ligands, or both, wherein the disease, disorder, or injury is cancer, and wherein the agent inhibits one or more Siglec-5 activities, wherein the cancer is selected from the group consisting of bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal cell cancer, renal pelvis cancer, leukemia, lung cancer, melanoma, non-Hodgkin’s lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, fibrosarcoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and multiple myeloma (see published claims 77-80). Wherein the individual is human [0057].
The `316 publication teaches and claims methods of inducing or promoting the survival, maturation, functionality, migration, or proliferation of one or more immune cells in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of an agent that decreases cellular levels of Siglec-5, inhibits interaction between Siglec-5 and one or more Siglec-5 ligands, or both, wherein the one or more immune cells are selected from the group consisting of dendritic cells, macrophages, neutrophils, NK cells, microglia, T cells, T helper cells, cytotoxic T cells, and any combination thereof, wherein the agent is an isolated anti-Siglec-5 antibody (see published claims 82-85).
Claim 2 is included because the `316 publication teaches under [0150] an agent candidate may be incubated with a Siglec-5, in vivo or in vitro, with a molecule cross-linker capable of covalently linking an agent candidate interacting with Siglec-5 to said Siglec-5 molecule. Subsequently, techniques, such as, but not limited to, mass spectrometry and/or Western blot, may be used to identify an agent candidate that may be capable of interacting with or otherwise inhibiting Siglec-5. For example, detection of Siglec-5covalently cross-linked with the agent candidate may indicate that the agent candidate may be capable of interacting with or otherwise inhibiting Siglec-5. Also, under Example 4, [0495] [0504] [0518] that antibodies 1B11, 1G4, 2G5, 4D5, 4D6, 5H2, 6G2, 7A5, 7E7, 8A1, 8C3, 9A5, 9B1, 10B6, 10D7, 10F9, 11C6, and 11H3 were able to block RBC binding to Siglec-5, thus indicating competitive binding of the antibodies to the ligand-binding site on Siglec-5, and their ability to inhibit the interaction between Siglec-5 and one or more Siglec-5 ligands (i.e., to block ligand binding to Siglec-5). Using a threshold value of 80% or higher of RBC binding to Siglec-5, it was found that all tested Siglec-5 antibodies were able to inhibit the interaction between Siglec-5 and one or more Siglec-5 ligands.
As for claim 35, the `316 publication teaches human Hs578T breast cancer cells, human SK-BR-3 breast cancer cells, human LNCaP(F) prostate cancer cells, human A375 melanoma cells, human Calu-6 lung cancer cells, human U-118-MG glioblastoma cells, human U-251-MG glioblastoma cells, human NCI-H23 lung cancer cells, and human NCI-H1563 lung cancer cells were also assessed for Siglec-5 ligand expression [0526]. [0527] FIG.15B shows that an inhibitory Siglec-5 ligand is expressed on breast cancer cells, prostate cancer cells, glioblastoma cells, and a subset of lung cancer cells. [0528] Without wishing to be bound by theory, identification of inhibitory sialic acid ligand expression on these tumor cells indicates a contributing mechanism by which cancer cells evade immune recognition and clearance. Sialic acid ligands on tumor cells can mediate immunosuppressive interactions via Siglec-5 expressed on myeloid and lymphoid immune cells. These results indicate that antibodies that remove Siglec-5 from the cell surface or block increased ligand interactions may relieve inhibitory effects of tumors on the immune system and enhance cancer therapy. Also, the instructions comprise a description of how to detect a Siglec-5 protein, for example in an individual, in a tissue sample, or in a cell. The kit and/or article of manufacture may further comprise a description of selecting an individual suitable for treatment based on identifying whether that individual has the disease and the stage of the disease [0446]. The `316 further teaches methods of assessing responsiveness of a subject in need thereof to an agent that binds or interacts with Siglec-5, the method comprising: a. measuring the expression levels of CD45+ and CD14+ on non-tumorigenic myeloid cells in a blood sample obtained from the subject prior to administering to the subject an anti-Siglec-5 antibody; b. administering to the subject a therapeutically effective amount of the agent; and c. measuring the expression levels of CD45+ and CD14+ on non-tumorigenic myeloid cells in a blood sample obtained from the subject after administration of the anti-Siglec-5 antibody, wherein a reduction in the levels of CD45+ CD14+ on non-tumorigenic myeloid cells after administration of the anti-Siglec-5 antibody indicates the subject is responsive to the agent [0399]. Moreover, the `316 publication teaches treatment cancers that tumors that express one or more Siglec-5 ligands [0023]. FIG. 14E depicts Siglec-5 ligand expression on primary rectal cancer tumor samples and primary colon cancer tumor samples.
The reference teachings anticipate the claimed invention.
9. Claims 1-4, 6, 8, 10, 12, 14-21, 25-27 and 30 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by patent WO2020023920 (IDS)/ US Patent.12258398 (102(a)(2)).
The US Patent `398 is 371 of the WO `920 publication and have identical teachings. The WO `920 publication is used in this rejection.
The `920 publication teaches and claims a monoclonal anti-Siglec-5 antibody, wherein the anti-Siglec-5 antibody decreases cellular levels of Siglec-5, and wherein the antibody does not bind Siglec-14, wherein the anti-Siglec-5 antibody decreases cellular levels of Siglec-5, and wherein the anti-Siglec-5 antibody does not inhibit the interaction between Siglec-5 and one or more Siglec-5 ligands, wherein the anti-Siglec-5 antibody does not inhibit the interaction between Siglec-5 and one or more Siglec-5 ligands, wherein the anti-Siglec-5 antibody decreases cell surface levels of Siglec-5, decreases intracellular levels of Siglec-5, decreases total levels of Siglec-5, or any combination thereof, wherein the anti-Siglec-5 antibody induces Siglec-5 degradation, Siglec-5 cleavage, Siglec-5 internalization, Siglec-5 shedding, downregulation of Siglec-5 expression, or any combination thereof, wherein the antibody decreases cellular levels of Siglec-5 in vivo, wherein the anti-Siglec-5 antibody induces reactive oxygen species (ROS) production in neutrophils, wherein the anti-Siglec-5 antibody induces neutrophil extracellular traps (NET) formation in neutrophils, wherein the anti-Siglec-5 antibody increases phagocytosis activity in macrophages, wherein the anti-Siglec-5 antibody increases expression of CD86 in myeloid derived suppressor cells, wherein the anti-Siglec-5 antibody increases expression of CCL4 in myeloid derived suppressor cells, wherein the anti-Siglec-5 antibody inhibits one or more Siglec-5 activities, wherein the cellular levels of Siglec-5 are measured on primary cells selected from the group consisting of dendritic cells, bone marrow-derived dendritic cells, monocytes, microglia, macrophages, neutrophils, B cells, and NK cells, or on cell lines, and wherein the cellular levels of Siglec-5 are measured utilizing an in vitro cell assay, wherein the anti-Siglec-5 antibody competes with one or more antibodies selected from the group consisting of S5-172, S5-174, S5-175, S5-176, S5-182, S5-183, S5-190, S5-202, S5-G-03, S5-G-07, S5-G-10, S5-172-H1, S5-172-H2, S5-172-H3, S5-172-H4, S5-172-H5, S5-172-H6, S5-174-H1, S5-174-H2, S5-174-H3, S5-174-H4, S5-174-H5, S5-174-H6, S5-174-H7, S5-174-H8, S5-G-03-H1, S5-G-03-H2, S5-G-03-H3, S5-G-03-H4, S5-G-03-H5, S5-G-03-H6, S5-G-03-H7, S5-G-03-H8, and S5-G-03-H9, and any combination thereof for binding to Siglec5, wherein the anti-Siglec-5 antibody binds to one or more amino acid residues within amino acid residues selected from the group consisting of: amino acid residues 268-278 of SEQ ID NO: 1 or amino acid residues on a Siglec-5 protein that correspond to amino acid residues 268-278 of SEQ ID NO: 1, amino acid residues 226-244 of SEQ ID NO: 1 or amino acid residues on a Siglec-5 protein that correspond to amino acid residues 226-244 of SEQ ID NO: 1, and amino acid residues 228-238 of SEQ ID NO: 1 or amino acid residues on a Siglec-5 protein that correspond to amino acid residues 228-238 of SEQ ID NO: 1, wherein the anti-Siglec-5 antibody binds to one or more amino acid residues within amino acid sequences selected from the group consisting of: the amino acid sequence LSWFQGSPALN (SEQ ID NO:221), the amino acid sequence QTITIFRNGIALEILQNTS (SEQ ID NO:220), and the amino acid sequence ITIFRNGIALE (SEQ ID NO:219), wherein the Siglec-5 protein is expressed on one or more cells selected from the group consisting of human dendritic cells, human macrophages, human neutrophils, human NK cells, human monocytes, human osteoclasts, human T cells, human T helper cell, human cytotoxic T cells, human granulocytes, and human microglia, wherein the anti-Siglec-5 antibody is a humanized antibody, a bispecific antibody, a multivalent antibody, a conjugated antibody, or a chimeric antibody, wherein the anti-Siglec-5 antibody is a bispecific antibody recognizing a first antigen and a second antigen, wherein the first antigen is Siglec-5 and the second antigen is ligands and/or proteins expressed on immune cells, wherein the ligands and/or proteins selected from the group consisting of PD1/PDL1, CD40, OX40, ICOS, CD28, CD137/4-1BB, CD27, GITR, PD-L1, CTLA4, PD-L2, PD-1, B7-H3, B7-H4, HVEM, LIGHT, BTLA, CD30, TIGIT, VISTA, KIR, GAL9, TIM1, TIM3, TIM4, A2AR, LAG3, DR-5, CD2, CD5, CD39, CD73, and phosphatidylserine (see published claims 1-68).
The `920 publication teaches and claims methods of preventing, reducing risk, or treating cancer, comprising administering to an individual in need thereof a therapeutically effective amount of the anti-Siglec-5 antibody, wherein the cancer expresses Siglec-5 or one or more Siglec-5 ligands, wherein the cancer is selected from the group consisting of bladder cancer, brain cancer, breast cancer, colon cancer, rectal cancer, endometrial cancer, kidney cancer, renal cell cancer, renal pelvis cancer, leukemia, lung cancer, melanoma, non-Hodgkin’s lymphoma, pancreatic cancer, prostate cancer, ovarian cancer, fibrosarcoma, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and multiple myeloma (see published claims 69-74), further comprising administering to the individual at least one antibody that specifically binds to an inhibitory checkpoint molecule, and/or one or more standard or investigational anti-cancer therapies, wherein the at least one antibody that specifically binds to an inhibitory checkpoint molecule is administered in combination with the anti-Siglec-5 antibody, wherein the at least one antibody that specifically binds to an inhibitory checkpoint molecule is anti-PD-L1 antibody, an anti-CTLA4 antibody, an anti-PD-L2 antibody, an anti-PD-1 antibody (see claims 81-83), further comprising administering to the individual at least one agonistic antibody that specifically binds to a stimulatory checkpoint protein, wherein the at least one agonistic antibody that specifically binds to a stimulatory checkpoint protein is administered in combination with the anti-Siglec-5 antibody. (see claims 88-89), wherein the individual is human [0056] . The antibody is obtained by immunizing agent will typically include the antigenic protein (e.g., a purified or recombinant Siglec-5 protein of the present disclosure) or a fusion variant thereof [0243].
The `920 publication teaches that the instructions comprise a description of how to detect a Siglec-5 protein, for example in an individual, in a tissue sample, or in a cell. The kit and/or article of manufacture may further comprise a description of selecting an individual suitable for treatment based on identifying whether that individual has the disease and the stage of the disease [0444] .
The reference teachings anticipate the claimed invention.
10. No claim is allowed.
11. The art made of record and not relied upon is considered pertinent to applicant's disclosure:
Li et al. Siglecs, Novel Immunotherapy Targets, Potentially Enhance The Effectiveness of Existing Immune Checkpoint Inhibitors in Glioma Immunotherapy. OncoTargets and Therapy 2019:12 10263–10273.
Li et al teaches that Siglec-5 showed a significant correlation with immunosuppression in
glioma. Siglec-5 is typically expressed in higher grade, IDH-wildtype, and mesenchymal subtype
gliomas. Siglec-5 had a similar immune function to TIM-3, while Siglec-16 was
similar to PD-L1, suppressing tumor immunity via different mechanisms. Joint use of Siglec inhibitors and immune checkpoint inhibitors could prolong the survival of glioma patients.
Li et al concluded that Siglec-5 suppressed tumor immunity in different ways. Joint
usage of inhibitors may be an effective means to improve the efficacy of glioma immunotherapy (abstract).
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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July 20, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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