Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Application Status
Claims 1-17 and 19-20 are pending and examined on the merits herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on page 21. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-17 and 19-20 are rejected under 35 U.S.C. 103 as being obvious over Fu (US 2023/0138315 A1; PTO-892) and Liu (US 2020/0369760 A1; IDS entered 01/18/2024).
The applied reference has a common applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claims 1 and 12, Fu teaches an anti-ANGPTL3 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region of an antibody, wherein: i) the heavy chain variable region has a HCDR1, a HCDR2 and a HCDR3 identical in sequences to those of a heavy chain variable region set forth in SEQ ID NO: 13, and the light chain variable region has a LCDR1, a LCDR2 and a LCDR3 identical in sequences to those of a light chain variable region set forth in SEQ ID NO: 14 (claim 1); a pharmaceutical composition, comprising: (A) a therapeutically effective amount of the anti-ANGPTL3 antibody or the antigen-binding fragment thereof according to claim 1, or the nucleic acid molecule according to claim 9, and (B) one or more pharmaceutically acceptable carriers, diluents, buffers or excipients (claim 11). SEQ ID NO: 13 has 100% sequence identity to the instant claimed SEQ ID NOs: 14-17; SEQ ID NO: 14 has 100% sequence identity to the instant claimed SEQ ID NOs: 11-13 and 18. Fu further teaches that the term “pharmaceutically acceptable carrier” refers to any inactive substance suitable for use in formulations for delivery of an antibody or an antigen-binding fragment. The carrier can be an anti-adhesive agent, binder, coating, disintegrant, filler or diluent, preservative (such as antioxidant, antibacterial or antifungal agent), sweetener, absorption delaying agent, wetting agent, emulsifier, buffer, etc. Examples of suitable pharmaceutically acceptable carriers include water, ethanol, polyol (such as glycerol, propanediol and polyethylene glycol), dextrose, vegetable oil (such as olive oil), saline, buffer, buffered saline, and isotonic agent such as sugar, polyol, sorbitol and sodium chloride (para 0094).
Regarding claim 11, Fu teaches the humanized antibody of the present disclosure also include humanized antibodies which were further subjected to CDR affinity maturation mutation by yeast display (para 0054).
Regarding claim 13, Fu teaches the anti-ANGPTL3 antibody or the antigen-binding fragment thereof according to claims 1, wherein the anti-ANGPTL3 antibody comprises a heavy chain and a light chain, wherein, (G) the heavy chain has at least 85% sequence identity to SEQ ID NO: 35, and/or the light chain has at least 85% sequence identity to SEQ ID NO: 36 (claim 6). SEQ ID NO: 35 and 36 have 100% sequence identity to instant claimed SEQ ID NO: 21 and 22 respectively.
Regarding claims 19-20, Fu teaches a method for treating a disease or a disorder in a subject in need thereof, the method comprising administering to the subject, a therapeutically effective amount of the anti-ANGPTL3 antibody or the antigen-binding fragment thereof according to claim 1, the nucleic acid molecule according to claim 9, or the pharmaceutical composition according to claim 11 (claim 14), wherein the disease or disorder is an ANGPTL3-associated disease (claim 15), wherein the disease or disorder is hypercholesterolemia, hyperlipidemia or an atherosclerotic disease (claim 16).
Fu does not teach the specific composition of the pharmaceutical composition.
Regarding claims 1-2, Liu teaches a liquid pharmaceutical formulation comprising: (a) an antibody or antigen-binding fragment that binds specifically to human angiopoietin-like protein 3 (ANGPTL3); (b) a buffer; (c) an organic cosolvent; and (d) at least one viscosity modifier, wherein the formulation has a pH of 6.0±0.3 (claim 1), wherein the buffer is histidine (claim 9).
Regarding claim 3, Liu teaches wherein the histidine concentration is from 5 mM±1 mM to 20 mM±4 mM (claim 10).
Regarding claim 4, Liu teaches wherein the antibody concentration is 150 mg/mL ± 22.5 mg/mL (claim 7).
Regarding claim 5, Liu teaches wherein the organic cosolvent is polysorbate (claim 12), wherein the organic cosolvent is polysorbate 80 (claim 15).
Regarding claim 6, Liu teaches wherein the polysorbate concentration is from 0.01% w/v ± 0.005% to 0.5% w/v ± 0.25% (claim 13). 0.1% w/v converts to 0.1 mg/ml.
Regarding claims 7-8, Liu teaches that in certain embodiments, a stabilizer is included in the formulation; the stabilizer is a sugar; the sugar is sucrose at a concentration of about 9% w/v (para 0019). 9%w/v of sucrose converts to 90mg/ml.
Regarding claim 9, Liu teaches wherein the at least one viscosity modifier is selected from the group consisting of arginine-HCl, sodium chloride, histidine-HCl, sodium acetate, calcium chloride, magnesium chloride, calcium acetate, and magnesium acetate (claim 16). Liu further teaches that magnesium acetate and calcium acetate were tested at 25mM with a significant reduction of viscosity (Table 1).
Regarding claim 10, Liu teaches the pharmaceutical formulations of the present invention may also comprise one or more excipients that serve to maintain a reduced viscosity including Sodium Acetate (pH 5) (para 0116). Liu further teaches in various embodiments; the antibody is provided at a concentration of 100 mg/mL±15 mg/mL (para 0013).
Regarding claim 14, Liu teaches that during the antibody purification process it may be desired or necessary to exchange one buffer for another to achieve appropriate excipient concentrations, antibody concentration, pH, etc. Buffer exchange can be accomplished, e.g., by ultrafiltration/diafiltration (UF/DF) using, e.g., a semi-permeable tangential flow filtration membrane (para 0118).
Regarding claims 15-16, Liu teaches the ANGPTL3 antibody was lyophilized and reconstituted for clinical use (table 12).
Regarding claim 17, Liu teaches a kit comprising a pharmaceutical formulation of claim 1, a container, and instructions (claim 37).
Regarding claims 19-20, Liu teaches a method for treating, preventing, or ameliorating any disease or disorder associated with ANGPTL3 activity or mediated by ANGPTL3 in a subject, comprising administering to the subject the pharmaceutical formulation of claim 1 (claim 39). Liu further teaches examples of diseases or disorders treatable using the formulations of the invention include, but are not limited to, those involving lipid metabolism, such as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including atherogenic dyslipidemia, diabetic dyslipidemia, hypertriglyceridemia, including severe hypertriglyceridemia with TG >1000 mg/dL, hypercholesterolemia, chylomicronemia, mixed dyslipidemia (obesity, metabolic syndrome, diabetes, etc.), lipodystrophy, lipoatrophy, and the like, which are caused by, for example, decreased LPL activity and/or LPL deficiency, decreased LDL receptor (LDLR) activity and/or LDL receptor deficiency (e.g., homozygous familial hypercholesterolemia with LDLR−/−), altered ApoC2, ApoE deficiency, increased ApoB, increased production and/or decreased elimination of very low-density lipoprotein (VLDL), certain drug treatment (e.g., glucocorticoid treatment-induced dyslipidemia), any genetic predisposition, diet, lifestyle, and the like. The formulations of the invention can also prevent or treat diseases or disorders associated with or resulting from hyperlipidemia, hyper-lipoproteinemia, and/or dyslipidemia, including, but not limited to, cardiovascular diseases or disorders, such as atherosclerosis, aneurysm, hypertension, angina, stroke, cerebrovascular diseases, congestive heart failure, coronary artery diseases, myocardial infarction, peripheral vascular diseases, and the like; acute pancreatitis; nonalcoholic steatohepatitis (NASH); blood sugar disorders, such as diabetes; obesity, and the like (para 0153).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to use a known pharmaceutical formulation as taught by Liu to the NAGPTL3 antibody taught by Fu. The ordinary artisan would have been motivated to do so because Fu and Liu both teach ANGPTL3 targeting antibodies in a pharmaceutical composition to treat ANGPTL3 associated diseases. It is routine in the art to optimize formulations of clinical antibodies to achieve the desired stability, viscosity, and concentration for clinical use.
Further one of ordinary skill in the art would recognize antibody concentration and formulation as result-effective variables and optimize them by routine experimentation. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine
experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). As
set forth at MPEP 2144.05 II. A: “Generally, differences in concentration or temperature
will not support the patentability of subject matter encompassed by the prior art unless
there is evidence indicating such concentration or temperature is critical.”
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 1-17 and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 11, 14, and 16-18 of copending Application No. 17/794,213 (patent has been allowed but has not yet been published) in view of Liu (US 2020/0369760 A1; IDS entered 01/18/2024).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 1 and 12, the copending claims teach an anti-ANGPTL3 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region and a light chain variable region of an antibody, wherein: i) the heavy chain variable region has a HCDR1, a HCDR2 and a HCDR3 identical in sequences to those of a heavy chain variable region set forth in SEQ ID NO: 13, and the light chain variable region has a LCDR1, a LCDR2 and a LCDR3 identical in sequences to those of a light chain variable region set forth in SEQ ID NO: 14 (claims 1-4); a pharmaceutical composition, comprising: (A) the anti-ANGPTL3 antibody or the antigen-binding fragment thereof according to claim 1, and (B) one or more pharmaceutically acceptable carriers, diluents, buffers or excipients. (claim 11). SEQ ID NO: 13 has 100% sequence identity to the instant claimed SEQ ID NOs: 14-17; SEQ ID NO: 14 has 100% sequence identity to the instant claimed SEQ ID NOs: 11-13 and 18.
Regarding claim 11, the copending claims teach the anti-ANGPTL3 antibody or the antigen-binding fragment thereof according to claim 5, wherein the heavy chain constant region is selected from the group consisting of human lgG1, lgG2, lgG3 and lgG4 constant regions, and the light chain constant region is selected from the group consisting of human K chain and A chain constant regions (claims 17-18).
Regarding claim 13, the copending claims teach the anti-ANGPTL3 antibody or the antigen-binding fragment thereof according to claims 1, wherein the anti-ANGPTL3 antibody comprises a heavy chain and a light chain, wherein, (G) the heavy chain has at least 85% sequence identity to SEQ ID NO: 35, and/or the light chain has at least 85% sequence identity to SEQ ID NO: 36 (claims 5-7). SEQ ID NO: 35 and 36 have 100% sequence identity to instant claimed SEQ ID NO: 21 and 22 respectively.
Regarding claims 19-20, the copending claims teach a method for treating a disease or a disorder inhibiting the activity of ANGPTL3 in a subject in need thereof, the method comprising administering to the subject, a therapeutically effective amount of the anti-ANGPTL3 antibody or the antigen-binding fragment thereof according to claim 1 or the pharmaceutical composition according to claim 11, wherein the subject in need thereof has a disease or disorder is related to positive cells of ANGPTL3 (claim 14), wherein the disease or disorder is hypercholesterolemia, hyperlipidemia or an atherosclerotic disease (claim 16).
The copending claims do not teach the specific composition of the pharmaceutical composition.
Regarding claims 1-2, Liu teaches a liquid pharmaceutical formulation comprising: (a) an antibody or antigen-binding fragment that binds specifically to human angiopoietin-like protein 3 (ANGPTL3); (b) a buffer; (c) an organic cosolvent; and (d) at least one viscosity modifier, wherein the formulation has a pH of 6.0±0.3 (claim 1), wherein the buffer is histidine (claim 9).
Regarding claim 3, Liu teaches wherein the histidine concentration is from 5 mM±1 mM to 20 mM±4 mM (claim 10).
Regarding claim 4, Liu teaches wherein the antibody concentration is 150 mg/mL ± 22.5 mg/mL (claim 7).
Regarding claim 5, Liu teaches wherein the organic cosolvent is polysorbate (claim 12), wherein the organic cosolvent is polysorbate 80 (claim 15).
Regarding claim 6, Liu teaches wherein the polysorbate concentration is from 0.01% w/v ± 0.005% to 0.5% w/v ± 0.25% (claim 13). 0.1% w/v converts to 0.1 mg/ml.
Regarding claims 7-8, Liu teaches that in certain embodiments, a stabilizer is included in the formulation; the stabilizer is a sugar; the sugar is sucrose at a concentration of about 9% w/v (para 0019). 9%w/v of sucrose converts to 90mg/ml.
Regarding claim 9, Liu teaches wherein the at least one viscosity modifier is selected from the group consisting of arginine-HCl, sodium chloride, histidine-HCl, sodium acetate, calcium chloride, magnesium chloride, calcium acetate, and magnesium acetate (claim 16). Liu further teaches that magnesium acetate and calcium acetate were tested at 25mM with a significant reduction of viscosity (Table 1).
Regarding claim 10, Liu teaches the pharmaceutical formulations of the present invention may also comprise one or more excipients that serve to maintain a reduced viscosity including Sodium Acetate (pH 5) (para 0116). Liu further teaches in various embodiments; the antibody is provided at a concentration of 100 mg/mL±15 mg/mL (para 0013).
Regarding claim 14, Liu teaches that during the antibody purification process it may be desired or necessary to exchange one buffer for another to achieve appropriate excipient concentrations, antibody concentration, pH, etc. Buffer exchange can be accomplished, e.g., by ultrafiltration/diafiltration (UF/DF) using, e.g., a semi-permeable tangential flow filtration membrane (para 0118).
Regarding claims 15-16, Liu teaches the ANGPTL3 antibody was lyophilized and reconstituted for clinical use (table 12).
Regarding claim 17, Liu teaches a kit comprising a pharmaceutical formulation of claim 1, a container, and instructions (claim 37).
Regarding claims 19-20, Liu teaches a method for treating, preventing, or ameliorating any disease or disorder associated with ANGPTL3 activity or mediated by ANGPTL3 in a subject, comprising administering to the subject the pharmaceutical formulation of claim 1 (claim 39). Liu further teaches examples of diseases or disorders treatable using the formulations of the invention include, but are not limited to, those involving lipid metabolism, such as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including atherogenic dyslipidemia, diabetic dyslipidemia, hypertriglyceridemia, including severe hypertriglyceridemia with TG >1000 mg/dL, hypercholesterolemia, chylomicronemia, mixed dyslipidemia (obesity, metabolic syndrome, diabetes, etc.), lipodystrophy, lipoatrophy, and the like, which are caused by, for example, decreased LPL activity and/or LPL deficiency, decreased LDL receptor (LDLR) activity and/or LDL receptor deficiency (e.g., homozygous familial hypercholesterolemia with LDLR−/−), altered ApoC2, ApoE deficiency, increased ApoB, increased production and/or decreased elimination of very low-density lipoprotein (VLDL), certain drug treatment (e.g., glucocorticoid treatment-induced dyslipidemia), any genetic predisposition, diet, lifestyle, and the like. The formulations of the invention can also prevent or treat diseases or disorders associated with or resulting from hyperlipidemia, hyper-lipoproteinemia, and/or dyslipidemia, including, but not limited to, cardiovascular diseases or disorders, such as atherosclerosis, aneurysm, hypertension, angina, stroke, cerebrovascular diseases, congestive heart failure, coronary artery diseases, myocardial infarction, peripheral vascular diseases, and the like; acute pancreatitis; nonalcoholic steatohepatitis (NASH); blood sugar disorders, such as diabetes; obesity, and the like (para 0153).
It would have been obvious to one of ordinary skill in the art to use a known pharmaceutical formulation as taught by Liu to the AGPTL3 antibody taught by the copending claims. The ordinary artisan would have been motivated to do so because the copending claims and Liu both teach ANGPTL3 targeting antibodies in a pharmaceutical composition to treat ANGPTL3 associated diseases. It is routine in the art to optimize formulations of clinical antibodies to achieve the desired stability, viscosity, and concentration for clinical use.
Further one of ordinary skill in the art would recognize antibody concentration and formulation as result-effective variables and optimize them by routine experimentation. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine
experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). As
set forth at MPEP 2144.05 II. A: “Generally, differences in concentration or temperature
will not support the patentability of subject matter encompassed by the prior art unless
there is evidence indicating such concentration or temperature is critical.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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