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 .
Application Status
Claims 35-54 are pending and examined on the merits herein.
Claim Objections
Claim 36 objected to because of the following informalities: line 2 of the claim recites “Down’s syndrome”; should read “Down syndrome”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 35-40 and 45-54 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.
Regarding claims 35, 52 and 54 the term “promote” in line 4 renders the claims indefinite as it is unclear whether the term “promote” requires the cis trans conversion, an increase in the rate of cis trans conversion or that there is no requirement for cis trans conversion but a possible increase in the conversion thereof.
As claims 36-40 and 46-51 depend from claim 35 and claim 53 depends from claim 52 without rectifying the issue identified above these claims are also included in this rejection.
Further, regarding claims 47 and 49-50, the phrase "optionally" used as exemplary language as it used not as an alternative limitation but in the format of: genus, optionally species. Therefore, the species following the term “optionally” are examples of the members of the genus. This is exemplary language and renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 45, the claim recites the limitation "the chimeric antibody" in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 45 is drawn to a humanized antibody and depends from claim 44 which is also drawn to a humanized antibody, therefore there is no antecedent basis for the term “the chimeric antibody”.
Claim Rejections - 35 USC § 112(a)
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.
Claims 35-40 and 46-54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The teachings of the specification and the claimed invention:
Claims 35, 52 and 54 are directed to a method of treatment comprising administering a genus of antibodies that bind to CD22 wherein the antibody promotes cis-trans conversion of CD22 and/ or induces internalization of CD22.
Claim 52 is further drawn to amyloid beta plaque removal or reduction of neuroinflammation.
Claim 54 is further drawn to internalization of amyloid beta by microglia cels.
The instant specification does not define the structural features of the paratope-epitope binding and the residues therein that facilitate binding of an antibody to CD22 that results in cis trans conversion. Claims 35-40 and 46-54 do not define the CDRs comprising the binding paratope of the antibody.
The instant specification discloses use of SM03 and SM06 their variations and derivations (para 0099; Table 1 and 2). Epitope mapping was not done for any of the clones.
The instant specification discloses that CD22 binds to its specific ligand distributed either on the same cell (cis-binding), or on a different cell (trans-binding) and that cis-binding of CD22 is demonstrated to exert a masking effect on the molecule, preventing the Siglec from forming cell to cell ligation (trans-binding). In resting B cells, CD22 is a prominent cis-ligand for itself, forming CD22 homo-oligomers. Trans-binding of CD22 results in the physical association of the Siglec with B-cell receptor (BCR) to exert a maximal inhibitory response, which is required for immune tolerance via eliciting inhibitory immunological signals (section 5.1, para 0047). The instant specification further discloses that the anti-CD22 antibodies disclosed herein promote cis-trans conversion of CD22 by disrupting the cis-binding of CD22 through steric hindrance on the surface of B-cells or microglia cells after CD22 the antibody is recycled to the surface which allows regaining immune tolerance of self-tissue and dampens pro-inflammatory cytokine release and further that by promoting trans-binding of CD22 to neuronal 2,6-sialic acid, the anti-CD22 antibodies disclosed herein inhibit phagocytosis of synapse and neuronal death, as well as suppress NF-KB signaling and interleukin-6 (IL-6) secretion in microglia cells. (para 0052).
The instant specification further teaches without being bound by theory, it is to be understood that the SM03, SM06, and other anti-CD22 antibodies disclosed herein can be used to achieve the above-mentioned therapeutic effect because they have at least one of the following functions or activities: (1) binding to an epitope that does not sterically interfere CD22 interaction with AP; (2) binding to the domain 2 of human CD22; (3) binding to the conformational epitope of human CD22 encompassing SEQ ID NO: 17-18; (4) disrupting cis-binding of CD22 homo-cluster; (5) promoting the cis-trans conversion of 2,6-sialic acid binding of CD22; (6) promoting trans-binding of CD22 to neuronal 2,6-sialic acid; (7) promoting CD22 internalization on, e.g., microglia cells, Ramos cell, and/or B cell, optionally at a rate of 50% of the surface CD22 internalized within 10 minutes; (8) promoting internalization of A3 in microglia cells; (9) suppressing pro-inflammatory cytokines, such as NFkB signaling, and IL-6 secretion; and (10) reducing neuroinflammation (para 00162).
As detailed below the state of the art does not recognize that a person of ordinary skill in the art could envision a genus of antibodies defined by epitope or function.
The disclosed antibody clone is not representative of the claimed genus of antibodies. This is because when antibodies are raised to an antigen each monoclonal antibody raised comes from one unique cell with unique CDRs which are responsible for antibody binding, such that the structure of CDRs for one antibody cannot be considered representative of other antibodies with different CDRs that bind the same antigen or even substantially the same epitope. Notably, the epitope structure that one antibody binds on an antigen, do not inform the skilled artisan as to what other antibodies would bind the same or substantially the same structure.
Claim analysis:
As detailed below, one skilled in the art would be unable to envision the entire genus of antibodies that would bind CD22 and promote cis trans conversion.
The state of the art as it applies to the claimed invention:
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Biodrugs (2007), 21 (3): 145-156; page 146, section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence.
Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al. Protein Science (2005), 14:246–248; page 246). 3D structural analyses of antibody-epitope binding highlights the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al. J Comput Chem (2005), 26(9):879-87; page 879).
Ladner (Biotechnology and Genetic Engineering Reviews (2007), 24(1): 1-30) teaches that competitive binding assays demonstrate that two antibodies bind to overlapping or non-overlapping epitopes but not the same epitope (page 3; paragraph 3), so for accurate epitope mapping techniques that can be used are large energy transfer between labeled antibody to an antigen, antigen fragment binding, competitive peptide and antigen binding to antibody, antigen or antibody mutation, antigen-antibody complex analysis by NMR, determination of the 3D crystal structure of the antigen-antibody complex or electron microscopy (pages 5-7).
There are antibodies that bind to CD22 known in the art and it is well recognized that binding to CD22 facilitates internalization. Shah (ImmunoTargets and Therapy, 10, 225–236; PTO-892) teaches that CD22 is a cell surface sialoglycoprotein uniquely present on B-cells and regulates B-cell function and proliferation, making it an appealing therapeutic target for autoimmune disorders and B-cell malignancies (abstract). Shah further teaches clinical trials with various CD22 antibodies for B cell malignancies (table 1). Ereño-Orbea (Nat Commun 8, 764 (2017); PTO-892) teaches characterization of the antigenic surface of CD22 recognized by two leading therapeutic antibodies in clinical trials: epratuzumab and pinatuzumab (page 5, col 2, para 2). Whether the known antibodies “promoted” cis trans conversion of could not be found in the prior art.
Regarding cis trans conversion of CD22 ligand binding Ereño-Orbea (Nat Commun 8, 764 (2017); PTO-892) teaches that although the role of CD22 as an inhibitory regulator of BCR signaling is well established, the question of how it binds ligands in both cis and trans is not fully understood (page 6, col 2, para 5). Crocker (Nat Rev Immunol 7, 255–266 (2007): PTO-892) teaches that cis ligands downregulate, but do not preclude, binding of ligands in trans, and that equilibrium-based binding of Siglecs to trans ligands can occur dynamically in the presence of cis ligands (page 258, col 1, para 1). Crocker further teaches that even when Siglecs are masked cis interactions, trans interactions might occur during an encounter with another cell or a pathogen expressing higher affinity ligands that can out-compete the cis interactions (Fig 4).
Accordingly, one skilled in the art would be unable to predict or envision a genus of antibodies that bind to CD22 and enable cis trans conversion. Since the disclosure fails to describe a sufficient number of species to describe the claimed genus, it is submitted that the written description requirement of 35 U.S.C. 112(a) has not been met.
Claim 36 is 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 a method of treating a neuroinflammation or a disease associated with beta amyloid by administering an antibody to CD22 wherein the disease is Alzheimer’s, prodromal Alzheimer’s, clinical or pre-clinical amyloid angiopathy, cerebral amyloid angiopathy, multi-infarct dementia, Parkinson’s disease, cognitive impairment, memory loss or vascular disorder caused by pathogenic amyloid beta in blood vessels, does not reasonably provide enablement for treatment of Down’s syndrome, glaucoma, or pre-eclampsia. 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. This is a scope of enablement rejection.
Nature of the invention/ Breadth of the claims. The claim is drawn to a method of treating a disease associated with beta amyloid or neuroinflammation comprising administering an anti-CD22 antibody that mediates cis trans conversion or internalization of CD22 wherein the disease is Alzheimer’s, prodromal Alzheimer’s, clinical or pre-clinical amyloid angiopathy, cerebral amyloid angiopathy, Parkinson’s disease, cognitive impairment, memory loss or vascular disorder caused by pathogenic amyloid beta in blood vessels, Down’s syndrome, multi-infarct dementia, glaucoma, or pre-eclampsia.
State of the prior art/ Predictability of the art. The state of the art does not recognize that administering an anti-CD22 antibody can achieve treatment Down’s syndrome, glaucoma, or pre-eclampsia.
Shah (ImmunoTargets and Therapy, 10, 225–236; PTO-892) teaches that CD22 is a cell surface sialoglycoprotein uniquely present on B-cells and regulates B-cell function and proliferation, making it an appealing therapeutic target for autoimmune disorders and B-cell malignancies (abstract). Shah further teaches clinical trials with various CD22 antibodies for B cell malignancies (table 1).
Okpala (Genet Mol Med. 2021; 3(1): 1-5; PTO-892) teaches that Down syndrome occurs when individuals experience abnormal cell division, resulting in a partial or complete copy of chromosome 21 that when unmanaged leads to serious health complications like ear infections, eye diseases, heart defects, hearing loss, seizures, gastrointestinal disorders, obesity, and obstructive sleep apnea (abstract). Okpala further teaches that medical practitioners cannot cure Down syndrome, but only manage its adverse signs and symptoms using medications for pain, dementia, depression, anti-psychotics, anti-convulsant, antibiotics for respiratory disorders as well as surgery and physical therapy (pages 2-3).
Li (Leukemia 40, 1542–1546 (2026); PTO-892) teaches use of CD22 antibody ADC inotuzumab ozogamicin to treat acute lymphoblastic leukemia in patients with Down syndrome (para 2). Li further teaches that patients with Down syndrome (DS) constitute ~3% of childhood B-cell acute lymphoblastic leukemia (B-ALL) and have inferior outcomes compared with patients without DS (para 1).
No prior art could be found that taught CD22 could be targeted for treatment of glaucoma or pre-eclampsia.
Working examples. There are no working examples of administration of an anti-CD22 antibody for any disease in the instant specification.
Guidance in the specification. The specification provides guidance towards using an anti-CD22 antibody for treatment of neuroinflammatory disease or disease mediated by amyloid beta, via various routes of administration.
The instant specification discloses that “anti-CD22 antibodies provided herein provide a novel mechanism of AP clearance that is not only highly efficient, but also associated with reduced vascular side effect like ARIA-E and/or ARIA-H. Unlike the AP-targeting antibodies, the anti-CD22 antibodies disclosed herein promotes AP clearance via CD22 internalization, which does not involve the cross-linking of the therapeutic antibodies with FcyR, thereby avoiding the subsequent pro-inflammatory response. Accordingly, provided here are methods of efficient AP clearance that have reduced vascular side effect. In some embodiments, methods provided herein do not cause vascular side effect” (para 0051).
All examples in the instant specification were performed on ex vivo cell cultures.
Amount of experimentation necessary. An extensive amount of additional research is required in order to determine how effective administering an anti-CD22 antibody, via the various disclosed routes of administration, to a subject would be to treat an amyloid beta or neuroinflammatory disease.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods.
Claim 46 is 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 a method of treating a neuroinflammation or a disease associated with beta amyloid by administering an antibody to CD22 via intracranial, intrathecal, or intraventricular administration, does not reasonably provide enablement for intravenous, intramuscular, subcutaneous, intraperitoneal, intranasal, parenteral, topical or intradermal administration. 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. This is a scope of enablement rejection.
Nature of the invention/ Breadth of the claims. The claim is drawn to a method of treating a disease associated with beta amyloid or neuroinflammation comprising administering an anti-CD22 antibody that mediates cis trans conversion or internalization of CD22 via intravenous, intramuscular, subcutaneous, intracranial, intrathecal, intraventricular, intraperitoneal, intranasal, parenteral, topical or intradermal administration
State of the prior art/ Predictability of the art. The state of the art does not recognize that administering an anti-CD22 antibody can achieve treatment Down’s syndrome, multi-infarct dementia or pre-eclampsia. Shah (ImmunoTargets and Therapy, 2021 10: 225–236; Published Jul7 6, 2021; PTO-892) teaches that CD22 is a cell surface sialoglycoprotein uniquely present on B-cells and regulates B-cell function and proliferation, making it an appealing therapeutic target for autoimmune disorders and B-cell malignancies (abstract). Shah further teaches clinical trials with various CD22 antibodies for B cell malignancies (table 1). However Yu et al. teaches that crossing the blood brain barrier would be necessary to treat neurodegenerative diseases such as Alzheimer’s disease and that 0.1-0.2% of circulating antibodies are found in the brain (Abstract; Neurotherapeutics. 10: 459-472, 2013). Yu et al. further teaches that receptor mediated transport can be utilized to facilitate transport of antibodies across the BBB (Figure 1b). However Yu teaches that crossing the blood brain barrier would be necessary to treat neurodegenerative diseases such as Alzheimer’s disease and that 0.1-0.2% of circulating antibodies are found in the brain (Abstract; Neurotherapeutics. 10: 459-472, 2013). Yu further teaches that receptor mediated transport can be utilized to facilitate transport of antibodies across the BBB (Figure 1b). Tashima (Pharmaceutics. 2022; 14(2):411; PTO-892) teaches that in general, Abs are unable to cross the BBB due to their large size and hydrophilic features but several Abs, such as DMR7, SKT82, and other anti-tau IgG molecules, have been reported to be successfully transported across the BBB in in vivo tests (Section 2.8.2) Tashima further teaches that BBB dysfunction is known to occur in AD , but delivery based on Ab leakage at a disordered BBB depends on the conditions of dysfunction, and may not be effective or appropriate for prophylactic use before AD pathogenesis (section 2.8.2). Tashima further teaches that bispecific mAbs with Fc domain targeting not only tau species in the brain but also receptors inducing transcytosis at the BBB represent a promising molecular design (fig 12). Therefore, an anti-CD22 antibody would not be effective against neurodegenerative disease via various routes of administration unless it was engineered to cross the BBB or directly administered via intra-cerebellar or intrathecal Therefore, an anti-CD22 antibody would not be effective against neurodegenerative disease via various routes of administration unless it was engineered to cross the BBB or directly administered via intracranial, intrathecal, or intraventricular.
Working examples. There are no working examples of in vivo administration of an anti-CD22 antibody in the instant specification.
Guidance in the specification. The specification provides guidance towards using an anti-CD22 antibody for treatment of neuroinflammatory disease or a disease mediated by amyloid beta, via various routes of administration, including intracranial, intrathecal, or intraventricular, but does not have any specific examples.
The instant specification further teaches that aducanumab was approved by FDA in June 2021 for the treatment of AD as the clinical studies consistently displayed reduction of amyloid plaques (para
Amount of experimentation necessary. An extensive amount of additional research is required in order to determine how effective administering an anti-CD22 antibody for treatment of neuroinflammatory disease or a disease mediated by amyloid beta, via various routes of administration recited.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to use the claimed methods.
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 35-40, 46, and 49 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ho (WO 2017/196432 A1; IDS entered 08/11/2024) as evidenced by Carnahan (Clin Cancer Res (2003) 9(10): 3982s–3990s; PTO-892).
Regarding claims 35-37, Ho teaches a method of determining whether a subject has, is at risk of having, or is in need of treatment for a neurodegenerative disease or disorder (claim 1), wherein the method designates the subject for treatment of one or more of Alzheimer's disease (claim 22), wherein the pharmaceutical composition comprises one or more of epratuzumab (claim 53).
Regarding claims 35 and 38-40, as evidenced by Carnahan, epratuzumab is a monoclonal humanized anti-human CD22 IgG1 antibody that is highly efficacious at inducing CD22 internalization (title and abstract).
Regarding claim 46, Ho teaches the compositions disclosed herein can be administered intravenously, intrathecally, or subcutaneously (para 00243).
Regarding claim 49, Ho teaches wherein the method comprises administering to the subject two or more agents that modulate, inhibit, block, decrease, increase, enhance, promote or elicit an acute or chronic immune response (claim 54).
Claim 54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pluvinage (Nature 568, 187–192 (2019); IDS entered 08/12/2024).
Regarding claim 54, Pluvinage teaches CypHer5E-labelled Aβ oligomers (1 mg/ml) were mixed with a mouse IgG1 isotype control antibody (MOPC21, BioXCell, 1 mg/ml) or anti-CD22 (Cy34, BioXCell, 1 mg/ml) and injected into the opposite hemispheres of aged mice using a stereotaxic apparatus; one microliter of the antibody–phagocytic target material mixture was injected and analyzed after 48 hours (methods: in vivo phagocytosis assay). As seen in Fig 3; CD22 inhibition with an anti-CD22 antibody restored deficient microglial phagocytosis ex vivo and in vivo; specifically demonstrated with amyloid beta oligomers (Fig 3h).
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.
Claims 41-45, 47-48, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Ho (WO 2017/196432 A1; IDS entered 08/11/2024) as evidenced by Carnahan (Clin Cancer Res (2003) 9(10): 3982s–3990s; PTO-892) as applied to claims 35-40, 46, and 49 above, and further in view of Leung (mAbs, 7(1): 66–76; PTO-892) and Li (Annals of the Rheumatic Diseases 2020;79:131; First published June 2, 2020; PTO-892).
The teachings of Ho as evidenced by Carnahan regarding claims 35-40 and 46 are detailed above.
Ho does not teach the anti-CD22 antibody is SM03 or SM06.
Leung teaches that there are a number of anti-CD22 antibodies in different
stages of clinical trials for treating lymphomas and other autoimmune diseases and that SM03 is one such antibody developed in China, where it is being evaluated clinically for treating non-Hodgkin’s lymphoma (NHL), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) (introduction, para 1).
Regarding claims 41-43, Leung teaches that SM03 is a chimeric antibody that targets the B-cell restricted antigen CD22 and leads to rapid internalization (abstract).
Regarding claims 44-45, Leung teaches that SM06 is a humanized counterpart of SM03 (page 71, col 1, para 2).
Regarding claims 47-48 and 51, Li teaches dosing of 3600mg cumulative dose of SM03 (group A, 600mg * 6 infusions at 0, 2, 4, 12, 14, and 16 week), 2400mg cumulative dose of SM03 (group B, 600mg*4 infusions at 0, 2, 12, and 14 week) (methods) and that SM03 was well tolerated with a good safety profile and efficacious against rheumatoid arthritis at these doses through 24 weeks of treatment (conclusion).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to substitute the SM03 clone as taught by Leung with the dosing schedule as taught by Li in the method of treating Alzheimer’s disease with an anti-CD22 antibody that induces internalization of CD22 as taught by Ho. The ordinary artisan would have been motivated to do so because Leung teaches that SM03 is an anti-CD22 antibody that leads to rapid internalization and Li teaches that SM03 was well tolerated with a good safety profile at the dosing schedule described. The ordinary artisan has a reasonable expectation of success to substitute SM03 for epratuzumab in the method of treating Alzheimer’s disease with an internalizing anti-CD22 antibody as these antibodies have the same target and same mechanism of action.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Ho (WO 2017/196432 A1; IDS entered 08/11/2024) as evidenced by Carnahan (Clin Cancer Res (2003) 9(10): 3982s–3990s; PTO-892) as applied to claims 35-40, 46, and 49 above, and further in view of Superson (European Journal of Clinical and Experimental Medicine. 17. 338-346; PTO-892).
The teachings of Ho as evidenced by Carnahan regarding claims 35-40 and 46 are detailed above.
Ho does not teach the specific additional therapeutic as recited in claim 50.
Superson teaches that aducanumab an antibody that recognizes conformational epitopes of aggregated β-amyloid forms resulted in a dose-dependent clinical response and a reduction in brain Aβ plaques were observed in PET in clinical trials (table 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to add an additional Alzheimer’s disease therapeutic as taught by Superson in the method of treating Alzheimer’s disease with an anti-CD22 antibody that induces internalization of CD22 as taught by Ho. The ordinary artisan would have been motivated to do so because Superson teaches that treatment with aducanumab resulted in a dose-dependent clinical response and a reduction in brain Aβ plaques were observed in PET in clinical trials. Therefore the ordinary artisan has a reasonable expectation of success to combine treatment with aducanumab and an anti-CD22 antibody to treat Alzheimer’s disease.
The rationale to combine two compositions taught by the prior art as useful for the same purpose to form a third composition to be used for the same purpose is prima facie obvious and is consistent with the exemplary rationales provided In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and discussed in M.P.E.P. § 2144. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
Claims 52-53 are rejected under 35 U.S.C. 103 as being unpatentable over Ho (WO 2017/196432 A1; IDS entered 08/11/2024) as evidenced by Carnahan (Clin Cancer Res (2003) 9(10): 3982s–3990s; PTO-892) as applied to claims 35-40, 46, and 49 above, and further in view of Pluvinage (Nature 568, 187–192 (2019); IDS entered 08/12/2024).
The teachings of Ho as evidenced by Carnahan regarding claims 35-40 and 46 are detailed above.
Ho does not teach a method of removing amyloid beta plaque or reduction of neuroinflammation.
Regarding claims 52-53, Pluvinage teaches CypHer5E-labelled Aβ oligomers (1 mg/ml) were mixed with a mouse IgG1 isotype control antibody (MOPC21, BioXCell, 1 mg/ml) or anti-CD22 (Cy34, BioXCell, 1 mg/ml) and injected into the opposite hemispheres of aged mice using a stereotaxic apparatus; one microliter of the antibody–phagocytic target material mixture was injected and analyzed after 48 hours (methods: in vivo phagocytosis assay). As seen in Fig 3; CD22 inhibition with an anti-CD22 antibody restored deficient microglial phagocytosis ex vivo and in vivo; specifically demonstrated with amyloid beta oligomers (Fig 3h).
Pluvinage further teaches that inhibition of CD22 promotes the clearance of myelin debris, amyloid-β oligomers and α-synuclein fibrils in vivo and that long-term central nervous system delivery of an antibody that blocks CD22 function reprograms microglia towards a homeostatic transcriptional state and improves cognitive function in aged mice (abstract). Pluvinage further teaches that CD22 blockade reduces the microglial expression of various neuromodulatory pro-inflammatory molecules.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to that use of an anti-CD22 antibody would result in the reduction of neuroinflammation and amyloid beta as taught by Pluvinage in the method of treating Alzheimer’s disease with an anti-CD22 antibody that induces internalization of CD22 as taught by Ho. The ordinary artisan would have been motivated to do so because Pluvinage teaches that inhibition of CD22 promotes the clearance of amyloid-β oligomers and that CD22 blockade reduces the microglial expression of various neuromodulatory pro-inflammatory molecules. Therefore the ordinary artisan has a reasonable expectation of success that the administration of an anti-CD22 antibody to treat Alzheimer’s disease would also result in the reduction of neuroinflammation.
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 35-43 and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-12 and 18-19 of copending Application No. 18/701,828 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 35-43, the copending claims teach a stable liquid pharmaceutical formulation of a therapeutically active anti-CD22 antibody, wherein said antibody is Suciraslimab (SM03) (claims 1-10), a method of treating an autoimmune disorder or disease in a subject in need thereof, said method comprising the step of administering the formulation according to claim 1 to said subject in an amount effective to bind and/or inhibit B-lymphocytes (claims 18-19), wherein said autoimmune disorder or disease is Alzheimer's Disease (claim 20).
Regarding claim 46, the copending claims teach wherein said formulation is suitable for intravenous infusion (claims 11-12).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 35-45 and 49-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13-18 of copending Application No. 18/858,323 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 35, 49-50, 52, and 54, the copending claims teach a method of promoting removal of beta-amyloid (Aβ) plaque in a subject in need thereof, said method comprising the step of administering to the subject a therapeutically effective amount of a bispecific antibody or antigen-binding fragment thereof that specifically binds on one end to an internalizing antigen expressed on the surface of cells in the neuroimmune system and to a toxic form of Aβ at the other end (claim 1), wherein the binding of the bispecific antibody or antigen-binding fragment to the internalizing antigen expressed on the surface of cells in the neuroimmune system (a) induces internalization of the surface receptors/antigens and/or (b) suppresses microglia, astrocyte, oligodendrocyte, pericyte brain endothelial cell or other neuro-immunological cell activation which promote neuro-inflammation (claims 2-4 and 7-8), wherein the internalizing antigen is CD22 (claim 5),
Regarding claims 36-37 and 53, the copending claims teach wherein the subject has been diagnosed with clinical or pre-clinical Alzheimer’s disease (claims 6 and 9-10).
Regarding claim 39, the copending claims teach wherein the bispecific antibody or antigen-binding fragment is an antibody selected from the group consisting of an IgGl antibody, an IgG2 antibody, an IgG3 antibody, and an IgG4 antibody (claims 11 and 13).
Regarding claims 38 and 40-43, the copending claims teach wherein the anti-CD22 binding moiety of the bispecific antibody or antibody fragment is SM03 (claims 14-16).
Regarding claims 44-45 and 51, the copending claims teach wherein the anti-CD22 binding moiety of the bispecific antibody or antibody fragment is SM06 (claims 17-18).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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