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 .
Applicant’s response filed on 4/22/2026 is acknowledged and fully considered.
Status of Application, Amendments, And/Or Claims
The amendments claims 101, 112-117 and the addition of claims 121-125 are made of record.
Claims 103-111 are canceled.
Claims 101-102 and 112-125 are pending.
Claims 118-120 remain withdrawn for being drawn for the reasons of record at pg. 2 of the office action of 1/26/2026.
Claims 101-102, 112-117 and 121-125 are under consideration.
Information Disclosure Statement
The Information Disclosure Statement filed on 3/6/2026 has been considered.
Response to Arguments
Claim Rejections - 35 USC § 112
The rejection of claims 103-105, and 109 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of Applicant’s amendments of claim 101 and the cancellation of claim 103-111.
Claim Rejections - 35 USC § 103-maintained
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 101-102 and 112-117 remain rejected and new claim 121-123 and 125 are rejected under 35 U.S.C. 103 as being unpatentable over Naito et al (US Pub. No. 2017/0260290, also published as US Pat. No. 10,570,215) in view of Partridge et al. (IDS, Pharm. Res. (2019) 36-71) as evidenced by Liu et al. (IDS, US Pub. No. 20120064086).
The instantly claimed invention is broadly drawn to a pharmaceutical formulation comprising:(i) about 40 mg/mL to about 160 mg/mL of an antibody that specifically binds to human endothelial lipase wherein the antibody comprises HCDR1-3 having amino acid sequence of SEQ ID NO: 1-3, respectively and LCDR1-3 having amino acid sequence of SEQ ID NO: 5-7, respectively, and (ii) about 50 mM to about 260 mM arginine salt (claims 101-102), wherein the formulation further comprises histidine (claim 112), wherein the pH is less than 7.0 (claim113), wherein the is suitable for a route of administration selected from the group consisting of intravenous injection, subcutaneous injection and intramuscular injection ( claim 116), wherein the formulation is reconstituted from a lyophilized formulation (claim 117), wherein the formulation comprises about 10-20 mM histidine and wherein formulation has a pH of 6.0.
Naito et al. teach a humanized monoclonal antibody or a fragment thereof that selectively inhibits the enzymatic activity of endothelial lipase and a pharmaceutical composition containing the same as an active ingredient for treatment of atherosclerosis or metabolic syndrome (abstract, col. 1, lines 29+). Naito et la teach an antibody having LCDRs 1-3 and HCDR1-3 which is identical to the instantly claimed LCDR1-3 and HCDR 1-3 (see sequence search results in PE2E). Naito et al do not teach that the composition comprises the antibody at about 40 mg/ml to about 160 mg/ml and arginine salt in about 50 mM to about 260 mM, and the composition further comprising histidine, wherein the pharmaceutical composition is reconstituted from a hydrolyzed formulation, and the formulation is suitable for administration for the group consisting of intravenous injection, subcutaneous injection and intracellular injection.
Partridge et al. making a composition comprising an antibody reconstituted from a lyophilized sample, wherein the antibody is 20 mg/mL to about 150 mg/mL (see Table 1 and pg. 18 of 21, (Conclusion and outlook)). They teach that the antibody is reconstituted in 80 mM arginine HCL, 120 mM sucrose and 20 mM histidine/histidine HCl (pg. 3, left col.). Regarding claim 113, they teach that the pH of the antibody buffer is 6 (which is less than pH 7). They teach reconstitution of antibody from lyophilized sample and study time needed for reconstitution. The resuspended sample would be suitable for administration to a subject by subcutaneous route. Additionally, because the antibody constituted from the lyophilized sample meets the limitation of claim 101, the composition would have viscosity of <= 30 cP at 18 °C and would have osmolality of about 260-500 mOsm/kg, unless evidence to contrary. Liu et al teach a stable formulation of an antibody having low turbidity and high concentration (title, abstract). They teach that the antibody can be in a range of 100-260 mg/ml, arginine HCl in an amount of 50-260 mg/ml, histidine 10-100 mM, polysorbate 0.01-0.1% wherein the pH is about 5.5 to 7.0, and kinetic viscosity is 50 cs or less and osmolarity is 200 -450 mOsm/kg (abstract, paragraph [0012]). Therefore, the formulation would be suitable for subcutaneous injection (as stated in the abstract by Liu et al).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a lyophilized composition of an antibody to reconstitute in arginine HCl having concentration of 50-260 mM and wherein the antibody is about 25-150 mg/mL as taught by Partridge et al. for an antibody that specifically binds to human endothelial lipase as taught by Naito et al. Partridge et al teach a lyophilized antibody in composition having 80 mM arginine HCl and histidine wherein the composition has pH 6.0 which would be suitable for subcutaneous administration and would have cP less than 50 as evidenced by Liu et al. Additionally, one would have been motivated to do so because Partridge et al. teach reconstitution of a lyophilized protein or an antibody from a lyophilized sample wherein the reconstitution is in 80 mM arginine HCl, histidine and the pH of the composition is 6.0. Further, one would have a reasonable expectation of success in using the antibody taught by Naito which specifically binds to human endothelial lipase and comprises the instantly claimed heavy chain amino acid sequence of SEQ ID NO: 4 and prepare a lyophilized sample for a long term storage that can be reconstituted in arginine HCl as taught by partridge. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
Applicants argue that Partridge is an analytical study and not a formulation study. They argue that Partridge teach reconstituting an antibody from lyophilized composition and they teach that it may take hours to fully reconstitute and may exhibit some undissolved particles. They argue that Liu discloses arginine formulation for proteins in general but Liu does not teach antibodies defined by specific CDRs (as in the instant claims). They argue that this can happen only because examiner’s rationale relies on impermissible hindsight reconstruction.
Applicants’ arguments have been fully considered but they are not persuasive because the instantly claimed antibody is taught by Naito et al and Partridge teach making a composition from a lyophilized sample, wherein the antibody is 20 mg/mL to about 150 mg/mL (see Table 1 and pg. 18 of 21, (Conclusion and outlook)). They teach that the antibody is reconstituted in 80 mM arginine HCL, 120 mM sucrose and 20 mM histidine/histidine HCl (pg. 3, left col.). They teach that the pH of the antibody buffer is 6 (which is less than pH 7). They teach reconstitution of antibody from lyophilized sample. Liu et al teach a stable formulation of an antibody having low turbidity and high concentration (title, abstract). They teach that the antibody can be in a range of 100-260 mg/ml, arginine HCl in an amount of 50-260 mg/ml, histidine 10-100 mM, polysorbate 0.01-0.1% wherein the pH is about 5.5 to 7.0.In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Additionally, in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
New Ground of rejection Necessitated by Applicant’s Amendments
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 101-102, 112-117 and 121-125 are rejected under 35 U.S.C. 103 as being unpatentable over Naito et al (previously applied, US Pub. No. 2017/0260290, also published as US Pat. No. 10,570,215) in view of Partridge et al. (IDS, Pharm. Res. (2019) 36-71), Liu et al. (IDS, US Pub. No. 20120064086) and Bee et al. (IDS, 2015/0239970).
The instantly claimed invention is broadly drawn to a pharmaceutical formulation comprising:(i) about 40 mg/mL to about 160 mg/mL of an antibody that specifically binds to human endothelial lipase wherein the antibody comprises HCDR1-3 having amino acid sequence of SEQ ID NO: 1-3, respectively and LCDR1-3 having amino acid sequence of SEQ ID NO: 5-7, respectively, and (ii) about 50 mM to about 260 mM arginine salt (claims 101-102), wherein the formulation further comprises histidine (claim 112), wherein the pH is less than 7.0 (claim113), wherein the is suitable for a route of administration selected from the group consisting of intravenous injection, subcutaneous injection and intramuscular injection ( claim 116), wherein the formulation is reconstituted from a lyophilized formulation (claim 117), wherein the formulation comprises about 10-20 mM histidine and wherein formulation has a pH of 6.0, wherein the surfactant is polysorbate 80 (claim 124)The pharmaceutical formulation of claim 101, wherein the pharmaceutical formulation further comprises: (iii) about 10 mM to about 20 mM of histidine and/or histidine salt; and (iv) about 0.02% to about 0.04% (w/v) of a surfactant, wherein the pharmaceutical formulation has a pH of about 6.0 and a viscosity of 30 cP at 18°C (claim 125).
Naito et al. teach a humanized monoclonal antibody or a fragment thereof that selectively inhibits the enzymatic activity of endothelial lipase and a pharmaceutical composition containing the same as an active ingredient for treatment of atherosclerosis or metabolic syndrome (abstract, col. 1, lines 29+). Naito et la teach an antibody having LCDRs 1-3 and HCDR1-3 which is identical to the instantly claimed LCDR1-3 and HCDR 1-3 (see sequence search results in PE2E). Naito et al do not teach that the composition comprises the antibody at about 40 mg/ml to about 160 mg/ml and arginine salt in about 50 mM to about 260 mM, and the composition further comprising histidine, wherein the pharmaceutical composition is reconstituted from a hydrolyzed formulation, and the formulation is suitable for administration for the group consisting of intravenous injection, subcutaneous injection and intracellular injection.
Partridge et al. making a composition comprising an antibody reconstituted from a lyophilized sample, wherein the antibody is 20 mg/mL to about 150 mg/mL (see Table 1 and pg. 18 of 21, (Conclusion and outlook)). They teach that the antibody is reconstituted in 80 mM arginine HCL, 120 mM sucrose and 20 mM histidine/histidine HCl (pg. 3, left col.). Regarding claim 113, they teach that the pH of the antibody buffer is 6 (which is less than pH 7). They teach reconstitution of antibody from lyophilized sample and study time needed for reconstitution. The resuspended sample would be suitable for administration to a subject by subcutaneous route. Additionally, because the antibody constituted from the lyophilized sample meets the limitation of claim 101, the composition would have viscosity of <= 30 cP at 18 °C and would have osmolality of about 260-500 mOsm/kg, unless evidence to contrary. Liu et al teach a stable formulation of an antibody having low turbidity and high concentration (title, abstract). They teach that the antibody can be in a range of 100-260 mg/ml, arginine HCl in an amount of 50-260 mg/ml, histidine 10-100 mM, polysorbate 0.01-0.1% wherein the pH is about 5.5 to 7.0, and kinetic viscosity is 50 cs or less and osmolarity is 200 -450 mOsm/kg (abstract, paragraph [0012]). Therefore, the formulation would be suitable for subcutaneous injection (as stated in the abstract by Liu et al). Neither Naito et al., Partridge et al. nor Liu et al teach that formulation comprises polysorbate 80 as a surfactant.
Bee et al. teach a stable formulation of antibody having high concentration about 150 mg/ml to 400 mg/ml and arginine having viscosity of less than 20 cP at 23° C (see paragraph [0010]). They teach the formulation further comprises polysorbate 80 about 0.01%-1.0%, histidine or histidine HCl in about 5 mM to 100mM and the formulation has viscosity =<cP and the pH of the formulation is 6.0 (see paragraph 0092] and claims 22-23).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use polysorbate 80 in a concentration of about 0.01% to 0.1% to make a stable formulation having cP <= 20 as taught by Bee et al using a lyophilized composition of an antibody to reconstitute in arginine HCl having concentration of 50-260 mM and wherein the antibody is about 25-150 mg/mL as taught by Partridge et al. for an antibody that specifically binds to human endothelial lipase as taught by Naito et al. Partridge et al teach a lyophilized antibody in composition having 80 mM arginine HCl and histidine, wherein the composition has pH 6.0 which would be suitable for subcutaneous administration and would have cP less than 50 as evidenced by Liu et al or a formulation having cP <= 20 as taught by Bee et al. Additionally, one would have been motivated to do so because Partridge et al. teach reconstitution of a lyophilized protein or an antibody from a lyophilized sample wherein the reconstitution is in 80 mM arginine HCl, histidine and the pH of the composition is 6.0 or Bee et al also teach a stable antibody formulation in arginine HCl further comprising a surfactant polysorbate 80 having pH 6.0 and viscosity <=20 cp (claims 21-22) . Further, one would have a reasonable expectation of success in using the antibody taught by Naito which specifically binds to human endothelial lipase and comprises the instantly claimed antibody prepared in a lyophilized sample for a long term storage that can be reconstituted in arginine HCl and polysorbate as taught by partridge, Liu and Bee et al. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GYAN CHANDRA whose telephone number is (571)272-2922. The examiner can normally be reached Mon-Friday 8:30AM-5:00P.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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