Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Application/Election/Restrictions
Claims 2-6, 10-12 and 15-18 are canceled. Claims 1, 7-9, 13-14 and 19-22 are pending in this application and under examination in this office action.
Claim Objections
Claims 1, 8-9 and 19-21 are objected to because of the following informalities: The recitation “MASP-2” is not a unique or common abbreviation in the art. Applicants are required to spell out “MASP-2” at the first usage. 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 1, 7-9, 13-14 and 21-22 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 pre-AIA the applicant regards as the invention.
Claims 1, 7-9, 13-14 and 21-22 are indefinite because:
i. The limitation “a portion of SEQ ID NO:6” recited in claims 1 and 21 is unclear. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “a portion of SEQ ID NO:6”. Since the metes and bounds are unknown, a skilled artisan cannot envision what portion of SEQ ID NO:6 that is bound by the claimed anti-MASP-2 inhibitory antibody or fragment thereof, and what the claimed anti-MASP-2 inhibitory antibody or fragment thereof is recited in the claim. Thus, the claims are indefinite.
ii. The term "high risk” in claim 7 or the term “reduced effector function” in claim 13 and 22 is a relative term which renders the claim indefinite. The term " high risk" or “reduced effector function” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of "high risk” or “reduced effector function”. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as "high risk” and what would be considered as having “reduced effector function” recited in the claim. Thus, the claims are indefinite.
iii. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
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 1, 7-9, 13-14 and 19-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reducing laser-induction choroidal neovascularization (CNV) in an animal model of laser-induction CNV by intraperitoneal administration of a structurally and functionally defined anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) to the animal model of laser-induction CNV as compared to a vehicle treatment (32%) or anti-VEGF treatment, does not reasonably provide enablement for a method for a method for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from all forms of angiogenesis-dependent cancer or inhibiting tumor angiogenesis in a mammalian subject with all forms of cancer using the claimed structurally and functionally undefined anti-MASP-2 inhibitory antibody or fragment thereof that specifically binds to a portion of SEQ ID NO:6 or the claimed structurally and functionally undefined MASP-2 inhibitor agent including a structurally and functionally undefined anti-MASP-2 inhibitory antibody or fragment thereof as broadly claimed. 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. In addition, the specification does not enable the invention of claims 1, 7-9 and 13-14 that is directed to a method of prevention and curing.
“There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue’. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)”. See MPEP § 2164.01.
Claims 1, 7-9 and 13-14 are directed to a method for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from an angiogenesis-dependent cancer, comprising administering to the subject an amount of an anti-MASP-2 inhibitory antibody or fragment thereof that specifically binds to a portion of SEQ ID NO:6.
Claims 19-22 are directed to a method of inhibiting tumor angiogenesis, comprising administering to a subject with cancer an amount of a MASP-2 inhibitory agent including an anti-MASP-2 antibody or fragment thereof.
The claims encompass methods of preventing, treating, reverting (curing) and/or delaying angiogenesis in all forms of angiogenesis-dependent cancer, all forms of solid tumors, blood borne tumors, high risk carcinoid tumors and tumor metastases using the claimed anti-MASP-2 inhibitory antibody or fragment thereof that specifically binds to a portion of SEQ ID NO:6 or the claimed MASP-2 inhibitory agent including an anti-MASP-2 antibody or fragment thereof including monoclonal antibody, recombinant antibody, antibody having reduced effector function, chimeric antibody, humanized antibody and human antibody in view of paragraphs [0117]-[0118], and paragraphs [0121]-[0124] and [0140]-[0167] of the published application.
The claims also encompass using a structurally and functionally undefined anti-MASP-2 inhibitory antibody or fragment thereof binding to a structurally and functionally undefined portion of SEQ ID NO:6, or a structurally and functionally undefined MASP-2 inhibitory agent including an a structurally and functionally undefined anti-MASP-2 antibody or fragment thereof, monoclonal antibody, recombinant antibody, antibody having reduced effector function, chimeric antibody, humanized antibody and human antibody in the claimed methods in view of paragraphs [0121]-[0124] and [0140]-[0167] of the instant specification (based on the published application).
The instant invention is based on findings that: i) IP administration of a mouse anti-MASP-2 MoAb (derived from anti-MASP-2 Fab2 antibody #11) at 1.0mg/kg to wild type mice 16 hours prior to laser-induction choroidal neovascularization (CNV) resulted in approximately 50% reduction in CNV at 7 day-post laser injury as compared to the mice treated isotype control MoAb; and a 0.3 mg/kg dose of anti-MASP-2 MoAb was not efficacious in reducing CNV (Example 14, Figure 16). 2) IP administration of an anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70 as listed on p.125) to wild type mice 8 days prior to laser CN induction resulted in reduction in CNV reduction (i.e. 20%, 25%, 18%) at 7 day-post laser jury as compared to vehicle treatment (32%) or anti-VEGF treatment (30%) (See Example 16, Figure 20).
Applicant extrapolates the above findings to the claimed methods for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from an angiogenesis-dependent cancer and inhibiting tumor angiogenesis in a subject with a cancer by the claimed anti-MASP-2 inhibitory antibody or fragment thereof or the claimed MASP-2 inhibitory agent including anti-MASP-2 antibody or fragment thereof.
First, Applicant is not enabled for a method of preventing/delaying, treating, and/or reverting (i.e. curing) angiogenesis in a subject suffering from an angiogenesis-dependent cancer or inhibiting tumor angiogenesis in a subject with a cancer using the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6, or the claimed MASP-2 inhibitory agent including an anti-MASP-2 antibody or fragment thereof.
The instant claims recite the limitation “preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from an angiogenesis-dependent cancer", which encompasses preventing and curing angiogenesis in all forms of angiogenesis-dependent cancer including tumor metastasis in view of paragraphs [0117]-[0118] of instant specification (based on published application).
However, neither the specification nor the prior art provides guidance as to how to prevent a subject who suffers from an angiogenesis-dependent cancer from having angiogenesis. The subject suffering from an angiogenesis-dependent cancer has already had tumor angiogenesis and so does the subject with a cancer because angiogenesis is the hallmark of cancer as evidenced by Albini et al. (Cancer Prev. Res. 2024;17:189-303. Doi:10.1158/1940-6207.CAPR-24-0085). Tumor angiogenesis is the hallmark or major feature of angiogenesis-dependent cancer. Tumor angiogenesis is a natural process in the subject with a cancer or an angiogenesis-dependent cancer. The tumor angiogenesis has existed in the subject with an angiogenesis-dependent cancer or a cancer, and thus cannot be prevented or delayed in the subject suffering from an angiogenesis-dependent cancer or a cancer. Neither the specification nor the prior art teaches that administration of the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 can prevent or delay the subject with an angiogenesis-dependent cancer from getting angiogenesis or happening of angiogenesis in the subject.
Further, currently there is no cure for such angiogenesis-dependent cancer including tumor metastasis in view of the factsheet of Metastasis (retrieved from the Cleveland Clinic website on 09/03/2026). Neither the specification nor the prior teaches that administration of the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 can treat or cure angiogenesis in all forms of angiogenesis-dependent cancer or inhibit tumor angiogenesis in all forms of cancer because MASP-2 is not the only cause of tumor angiogenesis in all forms of angiogenesis-dependent cancer or all forms of cancer. For example, there are at least six primary cellular mechanisms of tumor angiogenesis, including i) sprouting angiogenesis (SA); ii) vasculogenic mimicry (VM); iii) vessel intussusception; iv) vascular co-option; v) cancer stem cell-derived angiogenesis; and vi) bone marrow-derived angiogenesis as taught by Zhang et al. (Front Oncol. 2024; 14:1359069. Doi:10.3389/fonc.2024.1359069) and Subudhi et al. (Cell 2026; 189:2379-2415). These mechanisms encompass different signaling pathways, different growth factors such as VEGF/VEGFR, PDGF/PDGFR, different molecules such as Notch, Semaphorin, Ephrins and Slits and their receptors, and different cells involved as taught by Zhang et al. (Front Oncol. 2024; 14:1359069. Doi:10.3389/fonc.2024.1359069), Weis et al. (Nat. Med., 2011, 17: 1359-1370), Subudhi et al. (Cell 2026; 189:2379-2415), and Lugano et al. (Cell. Mol. Life Sci. 2020; 77:1745-1770. Doi.org/10.1007/s00018-019-03351-7). Neither the specification nor the prior art provides sufficient guidance as to how to cure tumor angiogenesis in angiogenesis-dependent cancer including tumor metastasis or inhibit tumor angiogenesis that is not mediated by MASP-2. The specification fails to provide sufficient guidance as to enable one of skill in the art to practice the invention as it pertains to a method of prevention or curing. Further, Applicant also fails to provide specific guidance as to what specific amount of the claimed the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 can be used and thus would be effective to prevent or cure tumor angiogenesis in all forms of angiogenesis-dependent cancer including tumor metastasis or inhibit tumor angiogenesis in all forms of cancer. Thus, a skilled artisan cannot contemplate a right amount to prevent the disease or to prevent a person from getting the disease or cure the disease.
Second, based on the specification, Applicant is enabled for reducing laser-induction choroidal neovascularization (CNV) in an animal model of laser-induction CNV by intraperitoneal administration of a structurally and functionally defined anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) to the animal model of laser-induction CNV as compared to a vehicle treatment (32%) or anti-VEGF treatment (see Example 14, Figure 16; and Example 16, Figure 20).
However, the claims are not limited to the agents and methods set forth above but are directed to prevention or treatment of all forms of angiogenesis-dependent cancer including tumor metastasis or inhibiting tumor angiogenesis in all forms of cancer and using a structurally and functionally undefined anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or structurally and functionally undefined MASP inhibitory agent including an anti-MASP-2 antibody or fragment thereof.
The specification fails to provide sufficient guidance to enable one of skill in the art to practice the full scope of the claimed invention without undue experimentation because there is no well-established structural and functional relationship or correlation between all forms of angiogenesis-dependent cancer including tumor metastasis or tumor angiogenesis in all forms of cancer and an animal model of laser-induction CNV.
The animal model of laser-induction CNV shown in Examples 14 and 16 is an acute laser injury to trigger a localized wound-healing and inflammation leading to neovascularization mimicking wet age-related macular degeneration, which is an experimental animal model to study abnormal blood vessel growth originating from the choroid into the retina as taught by Salas et al. (Biomedicines, 2023, 11:2445. Doi.org/10.3390/biomedicines11092445).
However, tumor angiogenesis in angiogenesis-dependent cancer including tumor metastasis or in different forms of cancer is a process of growing tumors, solid tumors due to hypoxia and secretion of pro-angiogenic factors such as VEGF/FGF/PDGF, anigopoietins and hypoxia-inducible factor HIF-1a and molecules involved in cellular mechanisms of sprouting angiogenesis, vascular co-option, vasculogenesis (bone-marrow-derived endothelial progenitors), intussusceptive vessel growth, vasculogenic mimicry, cancer cell-endothelial transdifferentiation to stimulate vascularization or the formation of new blood vessels to supply oxygen and nutrients. The molecular mechanisms of tumor angiogenesis in different forms of angiogenesis-dependent cancer including tumor metastasis or in different forms of cancer are different from each other (see p. 2387-2389, table 2 in Subudhi et al., Cell 2026; 189:2379-2415).
Neither the specification nor the prior art provides a well-established structural and functional relationship or correlation between treatment of all forms of angiogenesis-dependent cancer including tumor metastasis or inhibiting tumor angiogenesis in all forms of cancer by the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed MASP inhibitory agent and reduction of laser-induction CNV in an animal model of laser-induction CNV by the anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) in the animal model of laser-induction CNV as compared to a vehicle treatment or anti-VEGF treatment shown in Example 16 and Figure 20.
The specification provides insufficient guidance as to what structural and functional relationship between the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed MASP inhibitory agent and the anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) in reducing laser-induction CNV in an animal model of laser-induction CNV as compared to control or even in treatment of all forms of angiogenesis-dependent cancer including tumor metastasis or all forms of cancer, indicating undue experimentation is required by a skilled artisan while practicing the claimed invention.
While the skill level in the art is high, the level of predictability is low. The molecular mechanisms underlying different forms of angiogenesis-dependent cancer including tumor metastasis or different forms of cancer caused by different cellular mechanisms of tumor angiogenesis are different from each other. The specification provides insufficient guidance to demonstrate that administration of the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed MASP inhibitory agent including an anti-MASP-2 antibody or fragment thereof can treat all forms of angiogenesis-dependent cancer including tumor metastasis or all forms of cancer caused by different cellular mechanisms of tumor angiogenesis including angiogenesis not related to or mediated by MASP-2.
Each type of animal models of angiogenesis or tumor angiogenesis caused by different cellular mechanisms only reflects part of pathogenesis of the disease as taught by Makwana et al. (2023. Animal Models for Angiogenesis on Cancer Research. In: Pathak, S., Banerjee, A., Bisgin, A. (eds) Handbook of Animal Models and its Uses in Cancer Research. Springer, Singapore. doi.org/10.1007/978-981-19-3824-5_21). Applicant obviously intended to treat all forms of angiogenesis-dependent cancer including tumor metastasis or inhibiting tumor angiogenesis in all forms of cancer using the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed MASP inhibitory agent including an anti-MASP-2 antibody or fragment thereof. However, the specification provides no well-established structural and functional relationship or correlation between all forms of angiogenesis-dependent cancer including tumor metastasis or tumor angiogenesis in all forms of cancer and an animal model of laser-induction CNV. Thus, it is unpredictable whether one treatment for one specific disorder can be applied to another disorder, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
The specification also provides no well-established correlation among different forms of angiogenesis-dependent cancer including tumor metastasis or different forms of cancer caused by different cellular mechanisms of tumor angiogenesis. The specification fails to establish that different forms of angiogenesis-dependent cancer including tumor metastasis or different forms of cancer caused by different cellular mechanisms of tumor angiogenesis can be treated by the same drugs or same conditions or have the same effects in response to the same drugs. The specification fails to provide sufficient guidance or evidence to demonstrate that all forms of angiogenesis-dependent cancer including tumor metastasis or all forms of cancer caused by different cellular mechanisms of tumor angiogenesis including angiogenesis not mediated by MASP-2 can be treated or prevented or cured by the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed MASP inhibitory agent including an anti-MASP-2 antibody or fragment thereof because there is no well-established correlation between reduction of laser-induction CNV in an animal model of laser-induction CNV by the anti-MASP-2 MoAb OMS646 and pathogeneses or causes of tumor angiogenesis in all forms of angiogenesis-dependent cancer including tumor metastasis or all forms of cancer caused by different cellular mechanisms of tumor angiogenesis including angiogenesis not mediated by MASP-2. Thus, it is unpredictable whether the reduction of laser-induction CNV in an animal model of laser-induction CNV by the anti-MASP-2 MoAb OMS646 can be applied to other forms of tumor angiogenesis in all forms of angiogenesis-dependent cancer including tumor metastasis or all forms of cancer caused by different cellular mechanisms of tumor angiogenesis including angiogenesis not mediated by MASP-2, indicating that undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Further, the specification fails to provide sufficient guidance as to what other anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 are or what other MASP inhibitory agents including other anti-MASP-2 antibodies or fragments thereof are, and whether other anti-MASP-2 inhibitory antibodies or fragments thereof or other MASP inhibitory agents including other anti-MASP-2 antibodies or fragments thereof can be used in the claimed method because a single amino acid change on a molecule can abolish the binding ability of a molecule. For example, a substitution of lysine residue by glutamic acid at position 118 of acidic fibroblast growth factor results in a substantial loss of its biological activity including the binding ability to heparin and its receptor (Burgess et al. J of Cell Bio. 1990, 111:2129-2138). Even if an active or binding site were identified in the specification, they may not be sufficient, as the ordinary artisan would not immediately recognize that an active or binding site must assume the proper three-dimensional configuration to be active because conformation is dependent upon surrounding residues; i.e. substitution of non-essential residues can often destroy activity. In addition to a core determinant sequence, the protein-protein interaction also relies on the flanking or noncontiguous residues (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452). The optimal binding motif for a domain is not necessarily suitable for physiological or in vivo interaction. The predictive data always need to be validated by actual analyses in cells (see p. 445, the third column, second paragraph, Pawson et al. 2003, Science 300:445-452). Alaoui-lsmaili teaches that designing a mutein having predictable activities is difficult because of the complexity of the interactions between ligands and receptors (Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507). For example, given the complexity of BMP-BMP receptor interactions, it is difficult to design BMPs with improved affinity and/or specificity for one specific receptor. More importantly, predicting the in vivo biological activity of such altered BMPs remains a challenging undertaking (see p. 502, right col., 2th paragraph). Further, when multiple mutations are introduced, there is even less predictability because Guo et al. teaches that the effects of mutations on protein function are largely additive (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210). The specification fails to teach what other structures/amino acid sequences can or cannot not be included/changed in all anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 or all MASP inhibitory agents including all anti-MASP-2 antibodies or fragments thereof in order to preserve the activity of the anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) in reducing laser-induction CNV in an animal model of laser-induction CNV as compared to control, or even treating all forms of angiogenesis-dependent cancer including tumor metastasis or all forms of cancer caused by different cellular mechanisms of tumor angiogenesis including angiogenesis not mediated by MASP-2, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, the limited examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by one of skill in the art to perform in order to practice the full scope of the claimed invention as it pertains to methods for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from an angiogenesis-dependent cancer and inhibiting tumor angiogenesis by the claimed anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 or the claimed MASP inhibitory agents including the claimed anti-MASP-2 antibodies or fragments thereof.
Claim Rejections - 35 USC § 112
Claims 1, 7-9, 13-14 and 19-22 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.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 1, 7-9, 13-14 encompass using a genus of anti-MASP-2 inhibitory antibody or fragment thereof that specifically binding to a portion of SEQ ID NO:6 for preventing, treating, reverting and/or delaying angiogenesis in a subject suffering from a genus of angiogenesis-dependent cancer.
Claims 19-22 encompass using a genus of MASP-2 inhibitory agent including a genus of anti-MASP-2 antibody or fragment thereof for inhibiting tumor angiogenesis in a subject with a genus of cancer.
Claims 13 and 21-22 also encompass using a genus of anti-MASP-2 monoclonal antibody, a genus of anti-MASP-2 antibody having reduced effector function, a genus of anti-MASP-2 recombinant antibody, a genus of anti-MASP-2 chimeric antibody, a genus of anti-MASP-2 humanized antibody and a genus of anti-MASP-2 human antibody for preventing, treating, reverting and/or delaying angiogenesis in a genus of angiogenesis-dependent cancer or inhibiting tumor angiogenesis in a genus of cancer.
Applicant has not disclosed sufficient species for the broad genus of anti-MASP-2 inhibitory antibody or fragment thereof, the broad genus of MASP-2 inhibitory agent, the broad genus of anti-MASP-2 antibody having reduced effector function, the broad genus of anti-MASP-2 recombinant antibody, the broad genus of anti-MASP-2 chimeric antibody, the broad genus of anti-MASP-2 humanized antibody and the broad genus of anti-MASP-2 human antibody for preventing, treating, reverting and/or delaying angiogenesis in the broad genus of angiogenesis-dependent cancer or inhibiting tumor angiogenesis in the broad genus of cancer.
The specification only describes i) IP administration of a mouse anti-MASP-2 MoAb (derived from anti-MASP-2 Fab2 antibody #11) at 1.0mg/kg to wild type mice 16 hours prior to laser-induction choroidal neovascularization (CNV) resulted in approximately 50% reduction in CNV at 7 day-post laser injury as compared to the mice treated isotype control MoAb; and a 0.3 mg/kg dose of anti-MASP-2 MoAb was not efficacious in reducing CNV (Example 14, Figure 16); 2) IP administration of an anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70 as listed on p.125) to wild type mice 8 days prior to laser CN induction resulted in reduction in CNV reduction (i.e. 20%, 25%, 18%) at 7 day-post laser jury as compared to vehicle treatment (32%) or anti-VEGF treatment (30%) (See Example 16, Figure 20).
However, the claims are not limited to the method and the anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) set forth above but also encompass using a genus of structurally and functionally undefined anti-MASP-2 inhibitory antibody or fragment thereof that specifically binding to a portion of SEQ ID NO:6 and a genus of structurally and functionally undefined MASP-2 inhibitory agent including anti-MASP-2 antibody including a monoclonal antibody, antibody having reduced effector function, a recombinant antibody, a chimeric antibody, a humanized antibody and a human antibody for preventing, treating, reverting and/or delaying angiogenesis in the broad genus of angiogenesis-dependent cancer or inhibiting tumor angiogenesis in the broad genus of cancer.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, Applicant is in possession of using MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) for reducing laser-induction CNV in an animal model of laser-induction CNV as compared to a vehicle or anti-VEGF treatment.
However, Applicant is not in possession of using the claimed genus of structurally and functionally undefined anti-MASP-2 inhibitory antibody or fragment thereof that specifically binding to a portion of SEQ ID NO:6, the claimed genus of structurally and functionally undefined MASP-2 inhibitory agent including the genus of anti-MASP-2 antibody including a monoclonal antibody, antibody having reduced effector function, a recombinant antibody, a chimeric antibody, a humanized antibody and a human antibody for preventing, treating, reverting and/or delaying angiogenesis in the broad genus of angiogenesis-dependent cancer or inhibiting tumor angiogenesis in the broad genus of cancer.
The specification provides no well-established structural and functional relationship or correlation between reduction of laser-induction CNV in an animal model of laser-induction CNV by the anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) in the animal model of laser-induction CNV as compared to a vehicle treatment or anti-VEGF treatment shown in Example 16 and Figure 20 and treatment of all forms of angiogenesis-dependent cancer including tumor metastasis or inhibiting tumor angiogenesis in all forms of cancer by the claimed anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed MASP-2 inhibitory agent for preventing, treating, reverting and/or delaying angiogenesis in the broad genus of angiogenesis-dependent cancer or inhibiting tumor angiogenesis in the broad genus of cancer.
The specification provides no identification of any particular portion of the structure that must be conserved for the claimed genus of anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed genus of MASP-2 inhibitory agent including the genus of anti-MASP-2 antibody, monoclonal antibody, antibody having reduced effector function, recombinant antibody, chimeric antibody, humanized antibody and human antibody.
The instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of anti-MASP-2 inhibitory antibody or fragment thereof binding to a portion of SEQ ID NO:6 or the claimed genus of MASP-2 inhibitory agent including the genus of anti-MASP-2 antibody, monoclonal antibody, antibody having reduced effector function, recombinant antibody, chimeric antibody, humanized antibody and human antibody. There is no description of the conserved regions which are critical to the function of the genus claimed. There is no description of the sites at which variability may be tolerated and there is no information regarding the relation of structure of other anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 or other MASP-2 inhibitory agents including anti-MASP-2 antibodies, monoclonal antibodies, antibodies having reduced effector function, recombinant antibodies, chimeric antibodies, humanized antibodies and human antibodies to the function of the anti-MASP-2 MoAb OMS646 (a VH of SEQ ID NO: 67 and a VL of SEQ ID NO:70) in reducing laser-induction CNV in the animal model of laser-induction CNV as compared to a vehicle treatment or anti-VEGF treatment shown in Example 16 and Figure 20. Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to isolate and identify what other anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 or other MASP-2 inhibitory agents including anti-MASP-2 antibodies, monoclonal antibodies, antibodies having reduced effector function, recombinant antibodies, chimeric antibodies, humanized antibodies and human antibodies might be. Since the common characteristics/features of other anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 or other MASP-2 inhibitory agents including anti-MASP-2 antibodies, monoclonal antibodies, antibodies having reduced effector function, recombinant antibodies, chimeric antibodies, humanized antibodies and human antibodies are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the genus of anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 or other MASP-2 inhibitory agents including anti-MASP-2 antibodies, monoclonal antibodies, antibodies having reduced effector function, recombinant antibodies, chimeric antibodies, humanized antibodies and human antibodies.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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).
As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of anti-MASP-2 inhibitory antibodies or fragments thereof binding to a portion of SEQ ID NO:6 or other MASP-2 inhibitory agents including anti-MASP-2 antibodies, monoclonal antibodies, antibodies having reduced effector function, recombinant antibodies, chimeric antibodies, humanized antibodies and human antibodies, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483.
Therefore, the claimed methods have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(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.
Claims 1, 7-9, 13-14 and 19-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schwaeble et al. (US20070172483, published Jul 26, 2007, priority Jun 10, 2004) as evidenced by Weis et al. (Nat. Med., 2011, 17: 1359-1370).
Claims 1, 7-9 and 13-14 are directed to a method for preventing, treating, reverting and/or delaying angiogenesis in a mammalian subject suffering from an angiogenesis-dependent cancer, comprising administering to the subject an amount of an anti-MASP-2 inhibitory antibody or fragment thereof that specifically binds to a portion of SEQ ID NO:6. Claims 19-22 are directed to a method of inhibiting tumor angiogenesis, comprising administering to a subject with cancer an amount of a MASP-2 inhibitory agent including an anti-MASP-2 antibody or fragment thereof.
Schwaeble et al. (US20070172483) teach a method of treating malignancies (para. [0038]; [0283]-[0285]; [0289], claim 54), comprising administering to a subject in need thereof a MASP-2 inhibitory agent including an anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 (see the sequence alignment; para. [0038]; [0283]-[0285]; [0289], [0419]-claim 54) at a dose range of 0.010 to 10.0 mg/kg; 0.010 to 1.0 mg/kg; or 0.010 to 0.1 mg/kg of the subject body weight (see para. [0399]). The method disclosed by Schwaeble meets the limitations recited in instant claims 1, 7-9, 13-14 and 19-22 because the cancer, malignant tumor is an angiogenesis-dependent cancer and has tumor angiogenesis as evidenced by Weis et al. (see p. 1359-1365; Figures 1-2; boxes 1-2; Nat. Med., 2011, 17: 1359-1370). The amount recited in claims 8-9 is not limited to any specific amount. The dose range of 0.010 to 10.0 mg/kg; 0.010 to 1.0 mg/kg; or 0.010 to 0.1 mg/kg of the subject body weight disclosed by Schwaeble is identical to the dose range disclosed by the instant specification (see para. [0209] of the published Application).Schwaeble teaches an anti-MASP2 inhibitory antibody or fragment thereof, a MASP-2 inhibitory agent including an anti-MASP-2 antibody, a monoclonal antibody, a recombinant antibody, an antibody having reduced effector function, a chimeric antibody, a humanized antibody or a human antibody as in claims 13 and 22 (see para.[0138]-[0143]; claims 5-10;16-23). Schwaeble teaches different administration methods including subcutaneous, intraperitoneal, intra-muscular, intra-arterial, intravenous, or as an inhalant as in claim 14 (see para. [0415]-[0417]; [0428]-[0446]).
The limitation “preventing, treating, reverting and/or delaying angiogenesis” recited in the preamble of independent claim 1 or the limitation “inhibiting tumor angiogenesis” recited in the preamble of independent claim 19 is an intended use and is an inherent result or feature of administration of the claimed anti-MASP-2 inhibitory antibody or the claimed MASP-2 inhibitor agent. Schwaeble teaches a method of using the same material (i.e. the claimed anti-MASP2 inhibitory antibody or fragment thereof or the claimed MASP-2 inhibitory agent) and the same active step (i.e. administering to a subject in need thereof) in the same patient population (cancer or malignancy, which is an angiogenesis-dependent cancer and has tumor angiogenesis) as recited in instant claims. If the claimed method can prevent, treat, revert and/or delay angiogenesis or inhibit tumor angiogenesis, the Schwaeble’s method using the same material and the same active step in the same patient population can achieve the same intended result recited in independent claims 1 and 19. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999); Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) and MPEP § 2111.02-II. Note that
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997). If a prior art structure is capable of performing the intended use as recited in the preamble, then it meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997).
Thus, claims 1, 7-9, 13-14 and 19-22 are anticipated by Schwaeble et al. (US20070172483) as evidenced by Weis et al..
The sequence search results disclose as follows:
SEQ ID NO:6
ID AGE19333 standard; protein; 686 AA.
XX
AC AGE19333;
XX
DT 04-OCT-2007 (first entry)
XX
DE Human MBL-associated serine protease-2 polypeptide, SEQ ID 5.
XX
KW MBL-associated serine protease-2; therapeutic; enzyme inhibition;
KW meconium aspiration syndrome; wegener granulomatosis; vasculitis;
KW ulcerative colitis; thrombocytopenic purpura; takayasu's arteritis;
KW systemic lupus erythematosus; stress; spontaneous abortion; septic shock;
KW sepsis; rheumatoid arthritis; retinopathy; restenosis;
KW respiratory distress syndrome; pulmonary fibrosis; pulmonary disease;
KW psoriatic arthritis; psoriasis; pre-eclampsia; Parkinsons disease;
KW pancreatitis; osteoarthritis; non-insulin dependent diabetes; neuropathy;
KW myocardial infarction; myasthenia gravis; muscular dystrophy;
KW motor neurone disease; meningitis; membranous glomerulonephritis;
KW macular degeneration; lupus nephritis; Kawasaki disease;
KW juvenile rheumatoid arthritis; ischemia; irritable bowel syndrome;
KW interstitial cystitis; insulin dependent diabetes; infertility;
KW IgA nephropathy; Huntingtons chorea; Henoch-Schonlein purpura;
KW hemorrhagic shock; hemolytic uremic syndrome; hemolytic anemia;
KW hashimotos disease; gout; Goodpasture's syndrome; glomerulonephritis;
KW emphysema; diabetic angiopathy; cystitis; Crohns disease;
KW cerebrovascular trauma; cerebrovascular ischemia; cancer;
KW bullous pemphigoid; bronchiolitis; bleeding; bladder disease; asthma;
KW arthropathy; anxiety disorder; angiopathy; Alzheimers disease; vulnerary;
KW vasotropic; uropathic; tranquilizer; respiratory-gen.; osteopathic;
KW ophthalmological; nootropic; neuroprotective; nephrotropic;
KW muscular-gen.; immunosuppressive; hemostatic; gynecological;
KW gastrointestinal-gen.; dermatological; cytostatic; cns-gen.;
KW cerebroprotective; cardiovascular-gen.; cardiant; antiulcer; antithyroid;
KW antirheumatic; antipyretic; antipsoriatic; antiparkinsonian;
KW antiinflammatory; antiinfertility; antigout; antidiabetic;
KW anticonvulsant; antibacterial; antiasthmatic; antiarthritic; antianemic;
KW antiallergic; anti-abortive; enzyme; complement pathway;
KW immune inhibition; BOND_PC;
KW mannan-binding lectin serine protease 2, isoform 1, chain A;
KW mannan-binding lectin serine protease 2, isoform 1, chain B;
KW mannan-binding lectin serine protease 2 isoform 1 precursor;
KW MBL-associated plasma protein of 19 kD; small MBL-associated protein;
KW MBL-associated protein MAp19; MBL-associated serine protease 2;
KW MBL-associated serine protease(MASP)-2; Masp-2 protein; MASP2; sMAP;
KW MAP19; MASP-2; mannan-binding lectin serine protease 2;
KW mannan-binding lectin serine peptidase 2; GO4252; GO5509; GO6508; GO6958;
KW GO45087.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Peptide 1..15
FT /label= Signal_peptide
FT Protein 16..686
FT /label= Mature_MASP-2
XX
CC PN US2007172483-A1.
XX
CC PD 26-JUL-2007.
XX
CC PF 22-DEC-2006; 2006US-00645359.
XX
PR 10-JUN-2004; 2004US-0578847P.
PR 09-JUN-2005; 2005US-00150883.
PR 03-APR-2006; 2006US-0788876P.
XX
CC PA (OMER-) OMEROS CORP.
CC PA (UYLE-) UNIV LEICESTER.
XX
CC PI Schwaeble H, Stover CM, Tedford CE, Parent JB, Fujita T;
XX
DR WPI; 2007-662028/62.
DR N-PSDB; AGE19332.
DR PC:NCBI; gi21264363.
DR PC:SWISSPROT; O00187.
DR PC:BIND; 256563.
XX
CC PT Inhibiting in a subject mannan-binding lectin-associated serine protease
CC PT 2 (MASP-2)-dependent complement activation for treating or preventing
CC PT e.g., atherosclerosis by administering a MASP-2 inhibitory agent.
XX
CC PS Example 5; SEQ ID NO 5; 145pp; English.
XX
CC The present invention relates to methods of inhibiting the adverse
CC effects of MASP-2 dependent complement activation. The complement system
CC provides an early acting mechanism to initiate and amplify the
CC inflammatory response to microbial infection and other acute insults.
CC Complement system can be activated through two major systems namely
CC innate (lectin) and acquired (classical) wings of the complement immune
CC defense system. Lectins (mannan-binding lectin (MBL), H-ficolin, M-
CC ficolin, and L-ficolin) are the specific recognition molecules that
CC trigger the innate complement system and the system includes the lectin
CC pathway and the associated alternative pathway amplification loop. Human
CC MBL forms a specific and high affinity interaction through its collagen-
CC like domain with unique C1r/C1s-like serine proteases, termed MBL-
CC associated serine proteases (MASPs). C1q is the specific recognition
CC molecule that triggers the acquired complement system and the system
CC includes the classical pathway and associated alternative pathway
CC amplification loop. These two major complement systems are referred as
CC the lectin-dependent complement system and the C1q-dependent complement
CC system. In addition to its essential role in immune defense, the
CC complement system contributes to tissue damage in many clinical
CC conditions. So there is a need to develop therapeutically effective
CC complement inhibitors to prevent these adverse effects. It would be
CC highly desirable to specifically inhibit only the complement activation
CC system causing a particular pathology without completely shutting down
CC the immune defense capabilities of complement. The preferred protein
CC component to target in the development of therapeutic agents to
CC specifically inhibit the lectin-dependent complement system is MASP-2. Of
CC all the protein components of the lectin-dependent complement system,
CC only MASP-2 is both unique to the system and required for the system to
CC function and the plasma concentration of MASP-2 is among the lowest of
CC any complement protein, therefore, correspondingly low concentrations of
CC high-affinity inhibitors of MASP-2 may be required to obtain full
CC inhibition. The method of the invention comprises administering to the
CC subject an amount of a MASP-2 inhibitory agent effective to selectively
CC inhibit MASP-2-dependent complement activation without substantially
CC inhibiting C1q-dependent complement activation. The MASP-2 inhibitory
CC agent is a peptide derived from a polypeptide consisting of human MASP-2,
CC human MBL that inhibits MASP-2, human H-ficolin that inhibits MASP2,
CC human M-ficolin that inhibits MASP-2, human L-ficolin that inhibits MASP-
CC 2 or human C4 that inhibits MASP-2. The present invention provides
CC compositions for inhibiting the adverse effects of MASP-2-dependent
CC complement activation, comprising a MASP-2 inhibitory agent and a
CC pharmaceutically acceptable carrier. Methods are also provided for
CC manufacturing a medicament for use in inhibiting the effects of MASP-2-
CC dependent complement activation. The method is useful in inhibiting MASP-
CC 2-dependent complement activation in a subject for treating or preventing
CC ischemia-reperfusion injury, atherosclerosis, inflammatory
CC gastrointestinal disorder, pulmonary condition, musculoskeletal
CC condition, renal condition, skin condition, blood disorder, urogenital
CC condition, non-obese diabetes (Type-1 diabetes or Insulin-dependent
CC diabetes mellitus) or complications associated with Type-1 or Type-2
CC (adult onset) diabetes, malignancy, endocrine disorder or
CC ophthalmological condition. The present sequence is the protein sequence
CC of human MBL-associated serine protease-2 (MASP-2) which is encoded by
CC DNA located on chromosome 1 of the invention.
CC
CC Revised record issued on 29-AUG-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 686 AA;
Query Match 100.0%; Score 3686; Length 686;
Best Local Similarity 100.0%;
Matches 671; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 16 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 75
Qy 61 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 76 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 135
Qy 121 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 136 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 195
Qy 181 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 196 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 255
Qy 241 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 256 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 315
Qy 301 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 316 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 375
Qy 361 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 376 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 435
Qy 421 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 436 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 495
Qy 481 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 496 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 555
Qy 541 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 556 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 615
Qy 601 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 616 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 675
Qy 661 IPWIENIISDF 671
|||||||||||
Db 676 IPWIENIISDF 686
Claim Rejections - 35 USC § 102
Claims 1, 7-9, 13-14 and 19-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Demopulos et al. (WO2015058143, published Apr 23, 2015, priority Oct 17, 2013, as in IDS) as evidenced by Bhat et al. (eCancer, 2016; 10:649. DOI:10.3332/ecancer.2016.649) and Weis et al. (Nat. Med., 2011, 17: 1359-1370).
Demopulos et al. (WO2015058143) teach a method of treating systemic malignancies, cancer associated thrombotic microangiopathy (TMA) or TMA secondary to cancer (abstract; p. 31, lines 29-30; p. 36, line 27; p. 37, line 5; p. 56, line 13-p. 58, line 27), comprising administering to a subject in need thereof a MASP-2 inhibitory agent including an anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 including OMS646(see the sequence below; p.26-28; p. 49-50; p. 57-58; p.77-87) at a dose range of 0.010 to 10.0 mg/kg, preferably 0.010 to 1.0 mg/kg, more preferably 0.010 to 0.1 mg/kg of the subject body weight (see p. 102, lines 21-27), which is identical to the dose range disclosed by the instant specification (see para. [0209] of the published Application). The amount recited in claims 8-9 is not limited to any specific amount. The method disclosed by Demopulos meets the limitations recited in instant claims because the TMA secondary to cancer/cancer-associated TMA is caused by cancer or systemic malignancy or tumor metastasis as recited in claim 7 as evidenced by Bhat et al. (eCancer, 2016; 10:649. DOI:10.3332/ecancer.2016.649). Malignancy, cancer or systemic malignancy or tumor metastasis is a cancer or an angiogenesis-dependent cancer and has tumor angiogenesis as evidenced by Weis et al. (see p. 1359-1365; Figures 1-2; boxes 1-2; Nat. Med., 2011, 17: 1359-1370). Demopulos teaches an anti-MASP2 inhibitory antibody or fragment thereof, a MASP-2 inhibitory agent including OMS646 (a VH of SEQ ID NO:67 and a VL of SEQ ID NO:70), an anti-MASP-2 antibody, a monoclonal antibody, a recombinant antibody, an antibody having reduced effector function, a chimeric antibody, a humanized antibody or a human antibody as in claims 13 and 22 (see p.26-28; p. 49-50; p. 57-58; p.77-87). Demopulos teaches different administration methods including subcutaneous, intraperitoneal, intra-muscular, intra-arterial, intravenous, or as an inhalant as in claim 14 (see p. 37, lines 19-21; p. 56, lines 33-34).
The limitation “preventing, treating, reverting and/or delaying angiogenesis” recited in the preamble of independent claim 1 or the limitation “inhibiting tumor angiogenesis” recited in the preamble of independent claim 19 is an intended use and is an inherent result or feature of administration of the claimed anti-MASP-2 inhibitory antibody or the claimed MASP-2 inhibitor agent. Demopulos teaches a method of using the same material (i.e. the claimed anti-MASP2 inhibitory antibody or fragment thereof or the claimed MASP-2 inhibitory agent) and the same active step (i.e. administering to a subject in need thereof) in the same patient population (cancer or malignancy, which is an angiogenesis-dependent cancer and has tumor angiogenesis) as recited in instant claims. If the claimed method can prevent, treat, revert and/or delay angiogenesis or inhibit tumor angiogenesis, the Demopulos’ method using the same material and the same active step in the same patient population can achieve the same intended result recited in independent claims 1 and 19. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999); Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) and MPEP § 2111.02-II. Note that
If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997). If a prior art structure is capable of performing the intended use as recited in the preamble, then it meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997).
Thus, claims 1, 7-9, 13-14 and 19-22 are anticipated by Demopulos et al. (WO2015058143) as evidenced by Bhat et al. and Weis et al..
The sequence search results disclose as follows:
SEQ ID NO:6
ID BBY53066 standard; protein; 671 AA.
XX
AC BBY53066;
XX
DT 18-JUN-2015 (first entry)
XX
DE Human MASP-2 mature protein, SEQ ID 6.
XX
KW MASP-2 protein; MBL-associated serine protease 2;
KW Mannan-binding lectin serine protease-2;
KW Mannan-binding lectin-associated serine protease 2; antianemic;
KW antibody therapy; anticoagulant; antigen; antiphospholipid syndrome;
KW dermatological; enzyme inhibition; familial thrombotic microangiopathy;
KW gene silencing; hemolytic uremic syndrome; immunosuppressive;
KW malignant atrophic papulosis; nephrotropic; protein therapy;
KW rna interference; therapeutic; thrombolytic; thrombotic microangiopathy;
KW vasotropic.
XX
OS Homo sapiens.
XX
CC PN WO2015058143-A1.
XX
CC PD 23-APR-2015.
XX
CC PF 17-OCT-2014; 2014WO-US061236.
XX
PR 17-OCT-2013; 2013US-0892283P.
PR 03-JUL-2014; 2014US-0020845P.
XX
CC PA (OMER-) OMEROS CORP.
CC PA (UYLE-) UNIV LEICESTER.
XX
CC PI Demopulos GA, Dudler T, Schwaeble H;
XX
DR WPI; 2015-26373M/33.
DR N-PSDB; BBY53064, BBY53067.
XX
CC PT Inhibiting mannan-binding lectin-associated serine protease (MASP)-2-
CC PT dependent complement activation in subject suffering from, or at risk for
CC PT developing thrombotic microangiopathy comprises administering MASP-2
CC PT inhibitory agent.
XX
CC PS Claim 6; SEQ ID NO 6; 324pp; English.
XX
CC The present invention relates to a novel method for inhibiting a mannan-
CC binding lectin (MBL)-associated serine protease 2 (MASP-2)-dependent
CC complement activation in a subject suffering from, or at risk for
CC developing thrombotic microangiopathy (TMA). The method comprises:
CC administering a composition comprising an amount of a MASP-2 inhibitory
CC agent (preferably an anti-MASP-2 antibody, a lectin protein or a RNAi
CC molecule) to the subject. Also described are: (1) a method for inhibiting
CC MASP2-dependent complement activation in a subject suffering from Upshaw-
CC Schulman Syndrome; (2) a method for inhibiting MASP2-dependent complement
CC activation in a subject suffering from Degos disease; (3) a method for
CC inhibiting MASP2-dependent complement activation in a subject suffering
CC from catastrophic antiphospholipid syndrome; and (4) a method for
CC inhibiting MASP2-dependent complement activation in a subject suffering
CC from atypical hemolytic uremic syndrome. The method of the present is
CC useful for inhibiting MASP-2-dependent complement activation in a subject
CC suffering from thrombotic microangiopathy, Upshaw-Schulman Syndrome,
CC Degos disease, catastrophic antiphospholipid syndrome or atypical
CC hemolytic uremic syndrome, thereby treating the disease. The present
CC sequence represents a human MASP-2 mature protein which can be used as a
CC target antigen for the antibody of the present invention.
XX
SQ Sequence 671 AA;
Query Match 100.0%; Score 3686; Length 671;
Best Local Similarity 100.0%;
Matches 671; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 60
Qy 61 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 120
Qy 121 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 180
Qy 181 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 240
Qy 241 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 300
Qy 301 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 360
Qy 361 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 420
Qy 421 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 480
Qy 481 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 540
Qy 541 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 600
Qy 601 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 660
Qy 661 IPWIENIISDF 671
|||||||||||
Db 661 IPWIENIISDF 671
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 1, 7-9, 13-14 and 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 15-16 and 18 of U.S. Patent No. 8652477, claims 1-4, 7 and 10-14 of U.S. Patent No.10059776 or claims of U.S. Patent No. 10202465 as evidenced by evidenced by Weis et al. (Nat. Med., 2011, 17: 1359-1370). Although the claims at issue are not identical, they are not patentably distinct from each other because the method recited in claims of the issued patents anticipate instant claims.
Claims 1-11, 15-16 and 18 of US8652477 (the ‘477 patent) claim a method of inhibiting systemic coagulation in a subject suffering from disseminated intravascular coagulation that is secondary to a disease including malignancy (claim 2) using a MASP-2 inhibitory agent including n anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 including a monoclonal, recombinant, chimeric, humanized and human antibody.
Claims 1-4, 7 and 10-14 of US10059776 (the ‘776 patent) claim a method for reducing the likelihood that a subject at risk for developing atypical hemolytic uremic syndrome (aHUS) will suffering clinical symptoms associated with aHUS in a subject suffering from malignancy (claims 4 and 7) using a MASP-2 inhibitory agent including n anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 including a monoclonal, recombinant, chimeric, humanized and human antibody.
The cancer, malignant tumor is an angiogenesis-dependent cancer and has tumor angiogenesis as evidenced by Weis et al. (see p. 1359-1365; Figures 1-2; boxes 1-2; Nat. Med., 2011, 17: 1359-1370).
The limitation “preventing, treating, reverting and/or delaying angiogenesis” recited in the preamble of independent claim 1 or the limitation “inhibiting tumor angiogenesis” recited in the preamble of independent claim 19 is an intended use and is an inherent result or feature of administration of the claimed anti-MASP-2 inhibitory antibody or the claimed MASP-2 inhibitor agent. The claims of the issued patent claim a method of using the same material (i.e. the claimed anti-MASP2 inhibitory antibody or fragment thereof or the claimed MASP-2 inhibitory agent) and the same active step (i.e. administering to a subject in need thereof) in the same patient population (cancer or malignancy, which is an angiogenesis-dependent cancer and has tumor angiogenesis) as recited in instant claims. If the claimed method can prevent, treat, revert and/or delay angiogenesis or inhibit tumor angiogenesis, the method of the issued patents using the same material and the same active step in the same patient population can also achieve the same intended result recited in independent claims 1 and 19. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999); Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) and MPEP § 2111.02-II.
Therefore, claims 1, 7-9, 13-14 and 19-22 of the instant Application are not patentably distinct from claims 1-11, 15-16 and 18 of the ‘477 patent or claims 1-4, 7 and 10-14 of the ‘776 patent because claims 1, 7-9, 13-14 and 19-22 of the instant Application are anticipated by claims 1-11, 15-16 and 18 of the ‘477 patent or claims 1-4, 7 and 10-14 of the ‘776 patent as evidenced by Weis et al.
Conclusion
NO CLAIM IS ALLOWED.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US20130344073 teach a method of treating malignancy or thrombotic microangiopathy secondary to cancer, comprising administering to a subject in need thereof a MASP-2 inhibitory agent including an anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 (see the sequence alignment; para. [0357], claim 37).
SEQ ID NO:6
ID BBB15435 standard; protein; 686 AA.
XX
AC BBB15435;
XX
DT 13-FEB-2014 (first entry)
XX
DE Human MASP-2 protein, SEQ ID 5.
XX
KW MASP-2 protein; Mannan-binding lectin serine protease-2;
KW age related macular degeneration; aneurysm; antiallergic; antiarthritic;
KW antiasthmatic; antibody therapy; antiinflammatory; antimicrobial-gen.;
KW arthritis; asthma; bacterial infection; behcets disease; cancer;
KW disseminated intravascular coagulation; endophthalmitis;
KW fungal infection; glomerulonephritis; hemolytic uremic syndrome;
KW immunosuppressive; injury; juvenile rheumatoid arthritis; liver failure;
KW nephrotropic; neuromyelitis optica; neuroprotective; ophthalmological;
KW osteoarthritis; parasitic infection; pneumonia; psoriatic arthritis;
KW radiation sickness; renal disease; respiratory-gen.;
KW rheumatoid arthritis; sepsis; shock; skin burns; stroke; therapeutic;
KW thrombotic microangiopathy; transplant rejection; traumatic brain injury;
KW uropathic; vasotropic; viral infection; vulnerary.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Region 1..443
FT /note= "Alpha (A) chain"
FT Peptide 1..15
FT /label= Signal_peptide
FT Protein 16..686
FT /label= Mature_MASP-2_protein
FT Domain 300..431
FT /note= "CCP-1-CCP2 domain. This region is claimed in
FT claim 18"
FT Region 444..686
FT /note= "Beta (B) chain"
FT Domain 445..682
FT /note= "Serine protease binding domain. This region is
FT claimed in claim 18"
XX
CC PN US2013344073-A1.
XX
CC PD 26-DEC-2013.
XX
CC PF 18-JUN-2013; 2013US-00921139.
XX
PR 18-JUN-2012; 2012US-0661167P.
XX
CC PA (SCHW/) SCHWAEBLE H.
CC PA (DEMO/) DEMOPULOS G A.
CC PA (DUDL/) DUDLER T.
CC PA (GRAY/) GRAY P.
XX
CC PI Schwaeble H, Demopulos GA, Dudler T, Gray P;
XX
DR WPI; 2013-X37729/03.
DR N-PSDB; BBB15434.
XX
CC PT Inhibiting murine serine protease (MASP)-3-dependent complement
CC PT activation for treating disease or disorder e.g. age-related macular
CC PT degeneration and arthritis, involves administering composition comprising
CC PT MASP-3 inhibitory agent.
XX
CC PS Claim 6; SEQ ID NO 5; 197pp; English.
XX
CC The present invention relates to a method for inhibiting a MASP-3-
CC dependent complement activation in a subject suffering from, or at risk
CC for developing, a disease or disorder, where the disease or disorder is
CC selected from the group consisting of age-related macular degeneration,
CC arthritis (e.g., osteoarthritis, rheumatoid arthritis, juvenile
CC rheumatoid arthritis and psoriatic arthritis), disseminated intravascular
CC coagulation (which is secondary to sepsis, trauma, infection including
CC bacterial, viral, fungal or parasitic infection, malignancy, transplant
CC rejection, transfusion reaction, obstetric complication, vascular
CC aneurysm, hepatic failure, heat stroke, burn, radiation exposure, shock
CC or severe toxic reaction), thrombotic microangiopathy (e.g., hemolytic-
CC uremic syndrome (HUS), atypical hemolytic-uremic syndrome (aHUS) and
CC thrombotic thrombocytopenic purpura (TTP)), asthma, dense deposit
CC disease, pauci-immune necrotizing and crescentic glomerulonephritis,
CC traumatic brain injury, aspiration pneumonia, endophthalmitis,
CC neuromyelitis optica and Behcet's disease. The method involves
CC administering a composition comprising an effective amount of a MASP-3
CC inhibitory agent to inhibit MASP-3-dependent complement activation, to
CC the subject, where the MASP-3 inhibitory agent is a bispecific monoclonal
CC antibody. The invention also provides a method for preparing a medicament
CC for use in inhibiting the effects of MASP-3-dependent complement
CC activation or MASP-2-dependent complement activation, in the subject. The
CC method can also be used for treating the above mentioned disease of
CC disorder. The method has high sensitivity and specificity, and is cost-
CC effective. The composition avoids systemic side effects, and is nontoxic.
CC The present sequence is a human MASP-2 protein which can be used
CC regulating lectin pathway activation by competing for the binding of
CC MASPs to carbohydrate recognition complexes. Note: SEQ ID NO:36, 39 and
CC 41 are given in example 16, but the sequences were not shown in the
CC specification.
XX
SQ Sequence 686 AA;
Query Match 100.0%; Score 3686; Length 686;
Best Local Similarity 100.0%;
Matches 671; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 16 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 75
Qy 61 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 76 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 135
Qy 121 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 136 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 195
Qy 181 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 196 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 255
Qy 241 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 256 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 315
Qy 301 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 316 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 375
Qy 361 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 376 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 435
Qy 421 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 436 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 495
Qy 481 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 496 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 555
Qy 541 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 556 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 615
Qy 601 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 616 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 675
Qy 661 IPWIENIISDF 671
|||||||||||
Db 676 IPWIENIISDF 686
US20110311549 teach a method of treating malignancies (see para. [0329]; [0323]-[0325]), comprising administering to a subject in need thereof a MASP-2 inhibitory agent including an anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 (see the sequence alignment) at a dose of 0.010 to 10.0 mg/kg, preferably 0.010 to 1.0 mg/kg, more preferably 0.010 to 0.1 mg/kg of the subject body weight (see para. [0455]).
SEQ ID NO:6
ID AZQ79009 standard; protein; 686 AA.
XX
AC AZQ79009;
XX
DT 02-FEB-2012 (first entry)
XX
DE Human MBL-associated serine protease (MASP)-2 SEQ ID NO: 5.
XX
KW C1r; C1s-like serine protease; MASP2 protein;
KW Mannan-binding lectin serine protease-2;
KW adult respiratory distress syndrome; age related macular degeneration;
KW antiarthritic; antibody therapy; anticoagulant; antidiabetic; antigen;
KW antiinflammatory; antilipemic; arthritis; atherosclerosis;
KW blood clotting disorder; cancer; cardiant; cerebroprotective;
KW complement pathway; cytostatic; dermatological; dermatological disease;
KW diabetes mellitus; diabetic macular edema; diabetic nephropathy;
KW diabetic neuropathy; diabetic retinopathy; endocrine disease;
KW endocrine-gen.; gastrointestinal disease; gastrointestinal-gen.;
KW genitourinary disease; hematological disease; hematological-gen.;
KW hemolytic anemia; hemolytic uremic syndrome; hemorrhagic shock;
KW inflammatory disease; ischemia; lung disease; metabolic-gen.;
KW musculoskeletal disease; musculoskeletal-gen.; myocardial disease;
KW nephrotropic; neurological disease; neuroprotective; ocular disease;
KW ophthalmological; prophylactic to disease; renal disease;
KW reperfusion injury; respiratory-gen.; sepsis; septic shock; therapeutic;
KW thrombocytopenic purpura; uropathic; vascular disease; vasotropic;
KW vulnerary; BOND_PC;
KW mannan-binding lectin serine protease 2, isoform 1, chain A;
KW mannan-binding lectin serine protease 2, isoform 1, chain B;
KW mannan-binding lectin serine protease 2 isoform 1 precursor;
KW MBL-associated plasma protein of 19 kD; small MBL-associated protein;
KW MBL-associated protein MAp19; MBL-associated serine protease 2;
KW MBL-associated serine protease(MASP)-2; Masp-2 protein; MASP2; sMAP;
KW MAP19; MASP-2; mannan-binding lectin serine protease 2;
KW mannan-binding lectin serine peptidase 2; GO4252; GO5509; GO6508; GO6958;
KW GO45087.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Peptide 1..15
FT /label= Signal_peptide
FT Protein 16..686
FT /label= Mature_human_MASP-2_protein_AZQ79010. Used as
FT antigen for raising an anti-MASP-2 antibodies
FT Domain 16..308
FT /note= "CUB1-EGF-CUBII domain AZQ79014. Used as antigen
FT for raising an anti-MASP-2 antibodies"
FT Domain 16..181
FT /note= "CUB1-EGF domain AZQ79013. Used as antigen for
FT raising an anti-MASP-2 antibodies"
FT Domain 16..136
FT /note= "CUB1 domain AZQ79012. Used as antigen for raising
FT an anti-MASP-2 antibodies"
FT Binding-site 106..130
FT /note= "MBL binding region AZQ79021. Used as antigen for
FT raising an anti-MASP-2 antibodies"
FT Binding-site 116..123
FT /note= "MBL binding region core sequence AZQ79020. Used
FT as antigen for raising an anti-MASP-2 antibodies"
FT Domain 137..181
FT /note= "EGF-like domain AZQ79015. Used as antigen for
FT raising an anti-MASP-2 antibodies."
FT Domain 444..686
FT /note= "Serine protease domain AZQ79016. Used as antigen
FT for raising an anti-MASP-2 antibodies"
FT Active-site 614..638
FT /note= "Serine protease binding region active site
FT AZQ79023. Used as antigen for raising an anti-MASP-2
FT antibodies"
XX
CC PN US2011311549-A1.
XX
CC PD 22-DEC-2011.
XX
CC PF 08-APR-2011; 2011US-00083441.
XX
PR 10-JUN-2004; 2004US-0578847P.
PR 09-JUN-2005; 2005US-00150883.
PR 03-APR-2006; 2006US-0788876P.
PR 22-DEC-2006; 2006US-00645359.
PR 16-SEP-2009; 2009US-00561202.
PR 09-APR-2010; 2010US-0322722P.
PR 01-OCT-2010; 2010US-00896754.
XX
CC PA (UYLE-) UNIV LEICESTER.
CC PA (OMER-) OMEROS CORP.
XX
CC PI Schwaeble H, Tedford CE, Parent JB, Dudler T, Demopulos GA;
XX
DR WPI; 2011-Q90627/04.
DR N-PSDB; AZQ79008, AZQ79011.
DR PC:NCBI; gi21264363.
DR PC:SWISSPROT; O00187.
DR PC:BIND; 256563.
XX
CC PT Method for inhibiting mannose-binding protein-associated serine protease
CC PT (MASP)-2-dependent complement activation in subject suffering from e.g.
CC PT blood disorder, involves administering composition comprising MASP-2
CC PT inhibitory agent.
XX
CC PS Example 5; SEQ ID NO 5; 198pp; English.
XX
CC The present invention relates to a method of inhibiting mannan-binding
CC lectin (MBL)-associated serine protease (MASP, a C1r/C1s-like serine
CC protease)-2-dependent complement activation in a subject. The method
CC involves administering a composition comprising a MASP-2 inhibitory agent
CC to the subject. The MASP-2 inhibitory agent is an anti-MASP-2 monoclonal
CC antibody, or its fragments. In some embodiments, the MASP-2 inhibitory
CC agent inhibits cellular injury associated with MASP-2-mediated
CC alternative complement pathway activation, while leaving the classical
CC (C1q-dependent) pathway component of the immune system intact. The
CC invention also makes use of the composition for inhibiting the effects of
CC lectin-dependent complement activation in a subject. The method is useful
CC for preventing and treating diseases involving MASP-2-dependent
CC complement activation. The diseases are blood disorders (chosen from
CC sepsis, severe sepsis, septic shock, acute respiratory distress syndrome
CC resulting from sepsis, systemic inflammatory response syndrome,
CC hemorrhagic shock, hemolytic anemia, autoimmune thrombotic
CC thrombocytopenic purpura and hemolytic uremic syndrome); complement
CC mediated ischemia reperfusion injury (chosen from myocardial ischemia
CC reperfusion injury, gastrointestinal ischemia reperfusion injury,
CC cerebral ischemia reperfusion injury and renal ischemia reperfusion
CC injury); ophthalmologic conditions (preferably age-related macular
CC degeneration); diabetes; diabetic neuropathy, diabetic nephropathy,
CC diabetic retinopathy; diabetic macular edema; atherosclerosis; vascular
CC conditions (including cardiovascular conditions, cerebrovascular
CC conditions, peripheral vascular conditions, renovascular conditions, and
CC mesenteric/enteric vascular conditions); gastrointestinal disorders,
CC pulmonary disorders; inflammatory and non-inflammatory arthritides and
CC other musculoskeletal diseases; renal conditions; skin disorders; nervous
CC system diseases; urogenital disorders; malignancies; endocrine disorders;
CC and coagulopathies. The method is also useful for treating a subject or
CC who has undergone, is undergoing, or will undergo an organ or a tissue
CC (preferably kidney) transplant procedure. The present sequence is a human
CC MASP-2 protein. MASP-2 is used for producing anti-MASP-2 antibodies used
CC in the method of the invention.
CC
CC Revised record issued on 25-JAN-2012 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 686 AA;
Query Match 100.0%; Score 3686; Length 686;
Best Local Similarity 100.0%;
Matches 671; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 16 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 75
Qy 61 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 76 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 135
Qy 121 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 136 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 195
Qy 181 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 196 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 255
Qy 241 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 256 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 315
Qy 301 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 316 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 375
Qy 361 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 376 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 435
Qy 421 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 436 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 495
Qy 481 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 496 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 555
Qy 541 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 556 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 615
Qy 601 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 616 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 675
Qy 661 IPWIENIISDF 671
|||||||||||
Db 676 IPWIENIISDF 686
US20110091450 teaches a method of treating malignancy or thrombotic microangiopathy secondary to cancer, comprising administering to a subject in need thereof a MASP-2 inhibitory agent including an anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 (see the sequence alignment; para. [0291]-[0293]; [0297], claim 29).
SEQ ID NO:6
ID AZH44297 standard; protein; 686 AA.
XX
AC AZH44297;
XX
DT 04-AUG-2011 (revised)
DT 09-JUN-2011 (first entry)
XX
DE Human MBL-associated serine protease 2 (MASP-2), SEQ ID 5.
XX
KW MASP2; Mannan-binding lectin serine protease-2; aneurysm; antibacterial;
KW anticoagulant; antiinflammatory; antimicrobial-gen.;
KW blood clotting disorder; blood transfusion; cancer;
KW cardiovascular disease; cardiovascular-gen.; complement pathway;
KW cytostatic; dermatological; dermatological disease; drug discovery;
KW drug screening; endocrine disease; endocrine-gen.; enzyme inhibition;
KW genitourinary disease; gynecological; hematological disease;
KW hematological-gen.; hepatotropic; hyperthermia; immune disorder;
KW immunomodulator; immunosuppressive; inflammatory disease; injury;
KW liver failure; metabolic disorder; metabolic-gen.;
KW musculoskeletal disease; musculoskeletal-gen.;
KW neisseria meningitidis infection; neurological disease; neuroprotective;
KW obstetrics; otorhinolaryngological disease; otorhinolaryngological-gen.;
KW prophylactic to disease; respiratory disease; respiratory-gen.; sepsis;
KW skin burns; therapeutic; transplant rejection; uropathic; vulnerary;
KW BOND_PC; mannan-binding lectin serine protease 2, isoform 1, chain A;
KW mannan-binding lectin serine protease 2, isoform 1, chain B;
KW mannan-binding lectin serine protease 2 isoform 1 precursor;
KW MBL-associated plasma protein of 19 kD; small MBL-associated protein;
KW MBL-associated protein MAp19; MBL-associated serine protease 2;
KW MBL-associated serine protease(MASP)-2; Masp-2 protein; MASP2; sMAP;
KW MAP19; MASP-2; mannan-binding lectin serine protease 2;
KW mannan-binding lectin serine peptidase 2; GO4252; GO5509; GO6508; GO6958;
KW GO45087.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Peptide 1..15
FT /label= Siganl_peptide
FT Protein 16..686
FT /label= Mature_MBL-associated_serine_protease_2
FT Domain 16..136
FT /label=
FT C1r_C1s_sea_urchin_vegf_bone_morphogenic_protein_1
FT Region 106..130
FT /label= MBL_binding_region
FT Region 116..123
FT /label= MBL_binding_region
FT Domain 137..181
FT /label= Epidermal_growth_factor-like_domain
FT Domain 182..308
FT /label=
FT C1r_C1s_sea_urchin_vegf_bone_morphogenic_protein_2
FT Domain 444..686
FT /label= Serine-protease_domain
FT Active-site 614..638
FT /label= Serine-protease_active_site
XX
CC PN US2011091450-A1.
XX
CC PD 21-APR-2011.
XX
CC PF 15-OCT-2010; 2010US-00905972.
XX
PR 16-OCT-2009; 2009US-0279279P.
PR 09-APR-2010; 2010US-0322722P.
XX
CC PA (OMER-) OMEROS CORP.
CC PA (UYLE-) UNIV LEICESTER.
XX
CC PI Schwaeble H, Dudler T, Tedford CE, Parent JB, Demopulos GA;
XX
DR WPI; 2011-E20245/29.
DR N-PSDB; AZH44296.
DR PC:NCBI; gi21264363.
DR PC:SWISSPROT; O00187.
DR PC:BIND; 256563.
XX
CC PT Inhibiting MBL-associated serine protease (MASP)-2-dependent complement
CC PT activation in a subject suffering from, or at risk for developing, a
CC PT coagulation disorder, comprises administering MASP-2 inhibitory agent to
CC PT the subject.
XX
CC PS Example 5; SEQ ID NO 5; 167pp; English.
XX
CC The present invention relates to a method for inhibiting MBL-associated
CC serine protease (MASP)-2-dependent complement activation in a subject
CC suffering from, or at risk for developing, a coagulation disorder. The
CC method comprises administering to the subject an amount of a MASP-2
CC inhibitory agent effective to inhibit MASP-2-dependent complement
CC activation. The invention also includes: (1) a method for manufacturing a
CC medicament for use in inhibiting the effects of MASP-2-dependent
CC complement activation in living subjects suffering from a complement
CC mediated coagulation disorder; (2) a method for treating, preventing or
CC reducing the severity of disseminated intravascular coagulation in a
CC subject. The method of the invention is useful for inhibiting MASP-2-
CC dependent complement activation and for treating, preventing or reducing
CC the severity of disseminated intravascular coagulation and a disease or
CC condition selected from sepsis, trauma, malignancy, transplant rejection,
CC transfusion reaction, obstetric complication, vascular aneurysm, hepatic
CC failure, heat stroke, burn, radiation exposure, severe toxic reaction,
CC neurological trauma, and bacterial infection, where the bacterial
CC infection is a Neisseria meningitidis infection. The invention also
CC useful for treating dermatological disease, immune disorder,
CC cardiovascular disease, injury, neurological disease, metabolic disorder,
CC inflammatory disease, respiratory disease, musculoskeletal disease,
CC genitourinary disease, otorhinolaryngological disease, hematological
CC disease, endocrine disease. The present invention provides a MASP-2 to
CC initiate alternative complement pathway activation. The present sequence
CC is a human mature MBL-associated serine protease 2 (MASP-2) used in the
CC invention.
CC
CC Revised record issued on 25-JUL-2011 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 686 AA;
Query Match 100.0%; Score 3686; Length 686;
Best Local Similarity 100.0%;
Matches 671; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 16 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 75
Qy 61 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 76 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 135
Qy 121 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 136 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 195
Qy 181 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 196 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 255
Qy 241 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 256 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 315
Qy 301 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 316 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 375
Qy 361 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 376 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 435
Qy 421 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 436 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 495
Qy 481 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 496 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 555
Qy 541 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 556 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 615
Qy 601 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 616 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 675
Qy 661 IPWIENIISDF 671
|||||||||||
Db 676 IPWIENIISDF 686
WO2011006982 teaches a method of treating malignancy or thrombotic microangiopathy secondary to cancer, comprising administering to a subject in need thereof a MASP-2 inhibitory agent including an anti-MASP-2 inhibitory antibody binding to a portion of SEQ ID NO:6 (see the sequence alignment; para. [0291]-[0293]; [0297], claim 29).
SEQ ID NO:6
ID AZE74253 standard; protein; 686 AA.
XX
AC AZE74253;
XX
DT 17-MAR-2011 (first entry)
XX
DE Human MBL-associated serine protease-2 (MASP-2) SEQ ID NO: 9.
XX
KW Mannan-binding lectin serine protease-2; anticoagulant; antiinflammatory;
KW apoptosis; autoimmune disease; blood clotting disorder; cancer;
KW cardiovascular disease; complement pathway; cytostatic;
KW hematological disease; immune disorder; immunosuppressive;
KW inflammatory disease; neoplasm; protein therapy; therapeutic;
KW thrombolytic; thrombosis; BOND_PC;
KW mannan-binding lectin serine protease 2, isoform 1, chain A;
KW mannan-binding lectin serine protease 2, isoform 1, chain B;
KW mannan-binding lectin serine protease 2 isoform 1 precursor;
KW MBL-associated plasma protein of 19 kD; small MBL-associated protein;
KW MBL-associated protein MAp19; MBL-associated serine protease 2;
KW MBL-associated serine protease(MASP)-2; Masp-2 protein; MASP2; sMAP;
KW MAP19; MASP-2; mannan-binding lectin serine protease 2;
KW mannan-binding lectin serine peptidase 2; GO4252; GO5509; GO6508; GO6958;
KW GO45087.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Peptide 1..15
FT /label= Signal_peptide
FT Protein 16..686
FT /label= Mature_MBL-associated_serine_protease-2_protein
XX
CC PN WO2011006982-A2.
XX
CC PD 20-JAN-2011.
XX
CC PF 16-JUL-2010; 2010WO-EP060279.
XX
PR 17-JUL-2009; 2009EP-00165770.
PR 01-OCT-2009; 2009EP-00171941.
PR 05-MAR-2010; 2010US-0311049P.
XX
CC PA (RIGS-) RIGSHOSPITALET.
CC PA (UYKO-) UNIV KOBENHAVNS.
XX
CC PI Garred P, Glue TH, Skjodt M;
XX
DR WPI; 2011-A97093/10.
DR N-PSDB; AZE74254.
DR PC:NCBI; gi21264363.
DR PC:SWISSPROT; O00187.
DR PC:BIND; 256563.
XX
CC PT New ficolin-associated polypeptide useful as medicament for treating
CC PT conditions associated with inflammation, apoptosis and/or autoimmunity,
CC PT and coagulation, thrombotic or coagulopathic related diseases.
XX
CC PS Disclosure; SEQ ID NO 9; 120pp; English.
XX
CC The present invention relates to ficolin-associated proteins ((FAPs,
CC mannose/mannan-binding lectin (MBL)) and their derivatives. The FAP
CC polypeptides compete with MBL-associated serine protease (MASP)-1, MASP-
CC 2, MASP-3 or small MBL-associated protein (sMAP, MAP19) for binding to
CC MBL, ficolin-1, ficolin-2, ficolin-3, CIq, lung surfactant proteins SP-A
CC and/or SP-D and intracellular collagen-like defence molecules such as CL-
CC Ll. FAP was found to be an alternative transcript variant of MASP-1/MASP-
CC 3. FAP is partly identical to MASP-1 and MASP-3 but lacks a serine
CC protease domain and contains a novel exon encoding 17 amino acids
CC followed by a stop codon, which is spliced out in MASP-1 and MASP-3, and
CC does comprise the domains that are involved in binding to the initiators
CC of the lectin pathway of the complement system. The FAP proteins are
CC involved in regulation and inhibition of complement and coagulation
CC functions through competitions and displacement of the MASPs. The
CC polypeptides are used as biomarkers for diagnosing and treating
CC autoimmune diseases e.g., Addison's disease, autoimmune hemolytic anemia,
CC autoimmune thyroiditis, Crohn's disease and Graves' disease, conditions
CC associated with apoptosis, inflammatory disorders e.g., appendicitis,
CC peptic ulcer, gastric ulcer, duodenal ulcer, peritonitis and
CC pancreatitis, coagulation, thrombotic or coagulopathic related diseases
CC e.g., deep venous thrombosis, arterial thrombosis, post surgical
CC thrombosis and coronary artery bypass graft, and malignant diseases e.g.,
CC cancer. The invention also provides antibodies capable of recognizing the
CC FAP. The present sequence is a human MASP-2 protein of the invention. The
CC protein is encoded by gene located on chromosome 1p36-p36.2. Note: A
CC fragment of the present sequence corresponding to residues 16-296 is
CC specifically claimed in claim 9 (see AZE74274).
CC
CC Revised record issued on 04-MAR-2011 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 686 AA;
Query Match 100.0%; Score 3686; Length 686;
Best Local Similarity 100.0%;
Matches 671; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 16 TPLGPKWPEPVFGRLASPGFPGEYANDQERRWTLTAPPGYRLRLYFTHFDLELSHLCEYD 75
Qy 61 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 76 FVKLSSGAKVLATLCGQESTDTERAPGKDTFYSLGSSLDITFRSDYSNEKPFTGFEAFYA 135
Qy 121 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 136 AEDIDECQVAPGEAPTCDHHCHNHLGGFYCSCRAGYVLHRNKRTCSALCSGQVFTQRSGE 195
Qy 181 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 196 LSSPEYPRPYPKLSSCTYSISLEEGFSVILDFVESFDVETHPETLCPYDFLKIQTDREEH 255
Qy 241 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 256 GPFCGKTLPHRIETKSNTVTITFVTDESGDHTGWKIHYTSTAQPCPYPMAPPNGHVSPVQ 315
Qy 301 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 316 AKYILKDSFSIFCETGYELLQGHLPLKSFTAVCQKDGSWDRPMPACSIVDCGPPDDLPSG 375
Qy 361 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 376 RVEYITGPGVTTYKAVIQYSCEETFYTMKVNDGKYVCEADGFWTSSKGEKSLPVCEPVCG 435
Qy 421 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 436 LSARTTGGRIYGGQKAKPGDFPWQVLILGGTTAAGALLYDNWVLTAAHAVYEQKHDASAL 495
Qy 481 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 496 DIRMGTLKRLSPHYTQAWSEAVFIHEGYTHDAGFDNDIALIKLNNKVVINSNITPICLPR 555
Qy 541 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 556 KEAESFMRTDDIGTASGWGLTQRGFLARNLMYVDIPIVDHQKCTAAYEKPPYPRGSVTAN 615
Qy 601 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 616 MLCAGLESGGKDSCRGDSGGALVFLDSETERWFVGGIVSWGSMNCGEAGQYGVYTKVINY 675
Qy 661 IPWIENIISDF 671
|||||||||||
Db 676 IPWIENIISDF 686
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
September 4, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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