DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 22, and 45 have been canceled. Claims 18 and 25 have been amended. Claims 1-21, 23-44, and 46-51 are pending and examined on the merits.
Claim Objections
Claims 19, 20, 23 objected to because of the following informalities: the typographical error of “SEQ ID NO:14 (NYWM)” instead of “SEQ ID NO:14 (NYWMH)”. Appropriate correction is required.
Specification
The substitute specification, filed 5/10/2023, has been entered.
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 50 and 51 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “high” in claim 50 is a relative term which renders the claim indefinite. The term “high” 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..
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 1-5, 28-44, 46-51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-5, 28-44 and 46-51 are reliant upon the written description of a genus of monoclonal antibody or antigen-binding fragment characterized by binding to the linear epitope of SEQ ID NO:6 within the serine protease domain of MASP-2, wherein the antibody competes with C4 binding to MASP-2, forms a hydrogen bond with at least one of Lys 503 and/or His 508, forms a Wan der Waals contact with one or more of Asp 496, Lys 503, Ser 506, Pro 507, His 508 and Trp 513; has a binding affinity to MASP-2 of less than 20nM or less than 10nM; decreases C3b, C4 and MAC deposition under lectin-pathway specific assay conditions.
Section 2163 of the M.P.E.P states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
The specification has described the amino acid sequences of the heavy and light chains for the anti-MASP-2 antibodies of OMS850, OMS852, OMS854, OMS856, OMS858, OMS860, and OMS870 (page 40, Table 1A), and the CDR sequences for theOMS850, OMS860 and OMS870 antibodies (page 40, Table 1B). The specification has described the heavy and light chain and corresponding CDR sequences for “humanized and modified” versions of OMS850 (page 40, last sentence), but actually appears to describe the heavy and light chain and corresponding CDRS of modified forms of OMS852, OMS854, OMS856 and OMS858 (page 41, Table). This fails to provides an adequate written description of the genus of anti-MASP-2 antibodies that bind to the epitope of SEQ ID NO:6.
In claims 1-5, 28-44 and 46-51 the required antibodies are described only by functional characteristics. There is no correlation between a minimal structural requirement for the binding to MASP-2 coupled with these functional characteristics. One of skill in the art would not be able to envision the structure of the heavy and light chains or CDR sequences making up the antibody paratope beyond those anti-MASP-2 antibodies comprising the heavy and light chains or corresponding CDR sequences as described in the specification. One of skill in the art would reasonably conclude that applicant was not in possession of the claimed invention at the time of filing.
Claims 50 and 51are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating a mammalian subject suffering from a lectin-pathway disease or disorder comprising the administration of a MASP-2 inhibitory antibody or antigen-binding fragment sufficient to inhibit lectin pathway complement activation in the mammal, and a method of treating a subject at risk for developing a lectin-pathway disease or disorder wherein the disease or disorder to be prevented is the result of tissue or organ transplantation, graft v host disease, or a cardiovascular graft, does not reasonably provide enablement for the prevention of TMA, a renal condition resulting in a lectin-pathway disease, ischemia-reperfusion injury, a complication associated with diabetes, a cardiovascular disease, an inflammatory gastrointestinal disorder, a pulmonary disorder, an ophthalmic disease or disorder, DIC, , a veno-occulsive disease or diffuse alveolar hemorrhage.. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Claims 50 and 51 require, n part, the prevention of a lectin-pathway associated disease or disorder. When given the broadest reasonable interpretation, a “mammalian subject” includes humans and non-experimental animals and “prevention” requires that a subject without the disease or disorder is prevented from acquiring the disease or disorder by administration of the MASP-2 inhibitory antibody or antigen-binding fragment thereof r. In the case or a subject receiving a tissue or organ transplantation, or a cardiac graft, said subject will be free of the lectin pathway disease or disorder at the time of receiving the tissue or organ transplant, such as a cardiac graft and thus the potential lectin-pathway disease or graft vs-host could be prevented. It is noted that antibodies administered to a mammalian subject will have a finite lifetime in circulation. Thus, it would be necessary to administer the anti-MASP-2 antibodies to subjects prior to the onset of TMA, a renal condition resulting in a lectin pathway disorder, an ischemia reperfusion injury, a complication associated with diabetes, a cardiovascular disease or disorder beyond that resulting from a cardiac graft, an inflammatory gastrointestinal disorder, an ophthalmic disease or disorder, DIC, a pulmonary disorder, a veno-occlusive disease or diffuse alveolar hemorrhage. Since it would not be possible to determine if a mammalian subject will become afflicted with TMA, a renal condition, ischemia-reperfusion injury, a complication associated with diabetes, a cardiovascular disease or disorder other than a cardiac graft, a pulmonary disorder, an ophthalmic disease or disorder, DIC, or a veno-occlusive disease or diffuse alveolar hemorrhage prior to the actual onset of these diseases or disorder, one of skill I the art would not be able to determine which mammalian subject will acquire said diseases or disorder, and also when the mammalian subject will acquire the disease or disorder so that the anti-MASP-2 inhibitor antibody could be administered prior to onset such that the administered antibodies will be at a level in the circulation to provide efficacy. Given the lack of teachings and guidance in the specification regarding these issues, one of skill in the art would be subject to undue experimentation without reasonable expectation of success in the prevention of said diseases or disorders.
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 1-6, 9, 12, 13, 15, 24, 28, 29, 30-44 and 46-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No.12,091,468. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent anticipate the instant claims. The heavy chain comprising SEQ ID NO: 57, 53 and 18 of the ‘468 patent meets the limitations of “NXXMH”, wherein X at position 2 is “H” and X at position 3 is “W” in instant claims 6a, 9 and 15. The heavy chain comprising SEQ ID NO: 53 in claim 1 of the patent meets the limitations of instant claim 6a, wherein X at position 4 is “A”, and instant claims 12 and 15 requiring SEQ ID NO: 53. The heavy chain comprising the SEQ ID NO: 18 in claim 1 of the patent meets the limitations of instant claims 6a and 15 requiring SEQ ID NO:18. The light chain comprising the CDRs of SEQ ID NO: 32, 34 and 36 of the ‘468 patent meets the limitations of instant claim 6a, 13, and 15.
The heavy chain variable region of SEQ ID NO: 5 and light chain comprising SEQ ID NO” 47 of claim 2 of the patent meets the limitations of instant claim 6a, 9, 12, 15 and claims 24 and 25 for 100% identity to the instant SEQ ID NO: 50 and 47:
SEQ ID NO: 50
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SEQ ID NO: 47
DIQLTQSPSSLSASVGDRVTITCSASSSVRYMYWYQQKPGKAPKLLIYDTSNLASGVPSRFSGSGSGTDNTLTISSLQPEDFATYYCQQWSSYPLTFGQGTKVEIKR
Claims 3-16 of the patent anticipates instant claims 28-41, respectively. Claims 17 and 18 of the patent anticipates claims 42 and 43. The claims of the patent anticipate instant claims 2-5 as well, because the instant specification teaches that the inventive antibodies, in addition to binding to SEQ ID NO:6 have the property of inhibiting lectin pathway complement activation, competing with C4 binding to MASP-2, forming a hydrogen bond with His 508 of human MASP-2, forming Van Der Waals contact with one or more of Asp496, Lys503, Ser506, Pro507, His508 and TRp513. Thus, the antibodies of the claims of the ‘468 patent have these properties.
Regarding claims 44 and 46-49, it would have been prima facie obvious prior to the effective filing date to provide the polynucleotide encoding the light chain and polynucleotide encoding the heavy chain, either in two separate expression vectors, or combined in a single expression vectors and use the vector or vectors to transform a host cells in order to propagate and express the heavy and light chains of the inventive antibody of the ‘468 patent in culture. One of skill in the art would have been motivated to do so because the recombinant method of expression is standard in the art and one of skill in the art would be motivated to have a renewable supply of the light and heavy chains of the antibody. Thus, claims 44 and 46-49 are obvious over claims 1 and 2 of the patent.
Claims 1-10, 12, 13, 15, 16, 19-21, 28-32, 35-42, 44, 46-51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6, 7, 18-28, 136 of copending Application No. 18/181,437 of copending Application No. 18/181,437 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are either anticipated by, or obvious over the claims of the ‘437 application.
Claims 1 and 2 of the ‘437 application disclose a MASP-2 inhibitor which inhibits lectin pathway complement activation. Claim 4 specifies that the MASP-2 inhibitor of claim 1 is an antibody or antigen binding fragment thereof. Claim 6 of the ‘437 application discloses that the MASP-2 inhibitor is a human antibody, humanized antibody, chimeric antibody, urine antibody or antibody binding fragments of any of the aforesaid. Claim 7 of the ‘437 application discloses that the MASP-2 inhibitors a scFv, Fab, Fab’, F(ab’)2, a univalent antibody lacking a hinge or a whole antibody.
Claims 18 and 19 of the ‘437 application disclose an anit-MASP-2 antibody comprising the VH antibody chain SEQ ID NO:33 and VL of SEQ ID NO:23:
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYHMHWLRQAPGQGLEWIGDIDASDSETHYIEKFKDRATLTIDKSSSTAYMELSSLRSEDTAVYYCARGDITTTLRYFDVWGQGTLVTVSS
and
DIQLTQSPSSLSASVGDRVTITCSASSSVRYMYWYQQKPGKAPKLLIYDTSNLASGVPSRFSGSGSGTDNTLTISSLQPEDFATYYCQQWSSYPLTFGQGTKVEIKR
which meets the limitations of instant claims 6(a), 8, 12, 13, 15 and 21.
Claims 20 and 21 of the ‘437 application disclose an anit-MASP-2 antibody comprising the VH antibody chain SEQ ID NO:19 and VL of SEQ ID NO:23:
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which meets the limitations of claims 6(a), 9, 12, 13.
Claims 22 and 23 of the ‘437 application disclose an anit-MASP-2 antibody comprising the VH antibody chain SEQ ID NO:27 and VL of SEQ ID NO:30:
QVQLQQPGAELVRPGSSVRLSCKASGYTFTNYWMHWLKQRPIQGLEWIGDIDPSDSETHYIEKFKDKATLTIDKSSSTAYMHLSSLTSEDSAIYYCARGDITTTLRYFDVWGTGTTVTVSS
and
QIVLTQSPVIMSASPGEKVTMTCSASSSVRYMYWYQQKPGSSPRLLIYDTSNLASGVPVRFSGSGSGTSNSLTISRMEAEDAATYYCQQWSSYPLTFGAGTKLELKR
which meets the limitations of claims 6(a), 7, 10, 13, 15, 16, 19.
Claims 24 and 25 of the ‘437 application disclose an anit-MASP-2 antibody comprising the VH antibody chain SEQ ID NO:31 and VL of SEQ ID NO:23:
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Which meets the limitations of claims 6(a), 7, 10, 13, 15, 16 and 20.
Claims 26 and 27 of the ‘437 application disclose an anit-MASP-2 antibody comprising the VH antibody chain SEQ ID NO:32 and VL of SEQ ID NO:23:
QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYWMHWLRQAPGQGLEWIGDIDASDSETHYIEKFKDRATLTIDKSSSTAYMELSSLRSEDTAVYYCARGDITTTLRYFDVWGQGTLVTVSS
which meets the limitations of claims 6(a), 7, 12, 13, 15, 16 and 20.
Thus, the above claims of the ‘437 application anticipate instant claims 1-5, 35-41 because the antibodies of the ‘437 application have the same CDR sequences for binding to MASP-2 as claimed in the instant application. The instant specification teaches that the inventive antibodies, in addition to binding to SEQ ID NO:6 have the property of inhibiting lectin pathway complement activation, competing with C4 binding to MASP-2, forming a hydrogen bond with His 508 of human MASP-2, forming Van Der Waals contact with one or more of Asp496, Lys503, Ser506, Pro507, His508 and TRp513; bind to the serine protease domain of human MASP-2 with an affinity of less than 20nM or 10nM; decrease C3b, C4 and MAC deposition under lectin pathway-specific assay conditions. Thus, the antibodies of the claims of the ‘437 application have these properties. Claims 135-140, as drawn to a composition comprising a MASP-2 inhibitor, renders obvious instant claim 42.
Regarding claims 44 and 46-49, it would have been prima facie obvious prior to the effective filing date to provide the polynucleotide encoding the light chain and polynucleotide encoding the heavy chain, either in two separate expression vectors, or combined in a single expression vectors and use the vector or vectors to transform a host cells in order to propagate and express the heavy and light chains of the claimed antibodies of the ‘437 application in culture. One of skill in the art would have been motivated to do so because the recombinant method of expression is standard in the art and one of skill in the art would be motivated to have a renewable supply of the light and heavy chains of the antibody. Thus, claims 44 and 46-49 are obvious over claims 1 and 2 of the patent.
Claims 6 and 7 of the ‘437 application anticipate instant claims 28 and 29, respectively. Claim 6 specifying a “human antibody” and claim 7 specifying the “whole antibody” anticipate instant claim 30. Claim 6 specifying an antibody or antigen binding fragment thereof, anticipates instant claim 31. Claim 15 specifying an antibody o antigen-binding fragment thereof comprising a IgG region, renders obvious instant claim 32 because the various subtypes of IgG antibodies are well-known in the art
Claim 28 of the ‘437 application teaches the administration of a MASP-2 inhibitor to a mammalian subject in need of treatment of veno-occlusion. The claim does not specifically teach that the MASP-2 inhibitors are the inventive antibodies of the ‘437 application.
Section 804 IIb of the M.P.E.P. states;
The specification can be used as a dictionary to learn the meaning of a term in the patent claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999).
In the instant case, the ‘437 specification teaches:
In some embodiments, the MASP-3 and/or MASP-2 inhibitors are antibodies or antigen-binding fragments thereof (paragraph [0012]) including the antibodies comprising the variable chains of SEQ ID NO: 33 and SEQ ID NO:23 (paragraph [0113]); SEQ ID NO:19 and SEQ ID NO: 23 (paragraph [0109]); SEQ ID NO:27 and SEQ ID NO: 30 (paragraph [0110]); SEQ ID NO: 31 and SEQ ID NO: 23 (paragraph [0111]); and SEQ ID NO: 32 and SEQ ID NO: 23 (paragraph [0112]).
Thus, the claimed antibodies of the ‘437 application are identified as MASP-2 inhibitors of claim 28, thereby rendering obvious instant claims 50 and 51 as drawn to the inhibition of lectin complement pathway activation in a mammalian subject, wherein the subject is suffering from or at risk of veno-occlusive disease.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 11, 14, 17, 18, 25-27 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claim 23 would also be allowable when the typographical error is corrected and rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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