Office Action 2: Notice of Allowance (2025-01-23)

CLAIMS:
IN THE CLAIMS:

Set forth below in ascending order, with status identifiers, is a complete listing of all

claims currently under examination. Changes to any amended claims are indicated by \[\[double

brackets\]\], and/or underlining. This listing also reflects any cancellation and/or addition of claims.

1\. (Original) An injectable pharmaceutical formulation comprising:
a) 25 mg/mL of a fully human anti-interferon gamma (IFNy) monoclonal antibody; and b) 1.55 mg/mL L-histidine, 3.14 mg/mL L-histidine monohydrochloride, monohydrate,
0.05 mg/mL Polysorbate 80, and 7.31 mg/mL sodium chloride (NaCI),wherein the pH is between 5.8 and 6.2, and
wherein the antibody comprises a variable heavy chain complementarity determining region 1 (VH CDR1) comprising the amino acid sequence of SEQ ID NO: 1;
a variable heavy chain complementarity determining region 2 (VH CDR2) comprising the amino acid sequence of SEQ ID NO: 2;
a variable heavy chain complementarity determining region 3 (VH CDR3) comprising the amino acid sequence of SEQ ID NO: 3;
a variable light chain complementarity determining region 1 (VL CDR1) comprising the amino acid sequence of SEQ ID NO: 4;
a variable light chain complementarity determining region 2 (VL CDR2) region comprising the amino acid sequence of SEQ ID NO: 5; and a variable light chain complementarity determining region 3 (VL CDR3) region comprising the amino acid sequence of SEQ ID NO: 6.

2\. (Original) The formulation of claim 1, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 47, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48.

3\. (Original) The unit dose vial of claim 1, wherein the antibody is solubilized in the solution such that the solution is clear, colorless, and without precipitate.

4\. (Original) A method of treating a condition in a human subject by administering the formulation of claim 1, wherein the condition is primary hemophagocytic lymphohistiocytosis (HLH) or secondary HLH.

5\. (Original) The method of claim 4, wherein the human subject is pediatric or adult.

6\. (Currently Amended) A unit dose vial comprising, 2 mL, \[\[4mL, \]\] 10 mL or 20 mL of a fully human anti-interferon gamma (IFNy) monoclonal antibody solution suitable for injection,wherein the solution comprises 1.55 mg/mL L-histidine, 3.14 mg/mL L-histidine monohydrochloride, monohydrate, 0.05 mg/mL Polysorbate 80, and 7.31 mg/mL sodium chloride (NaCI),
wherein the pH of the solution is between 5.8 and 6.2,
wherein the concentration of antibody is at 25 mg/mL, and
wherein the antibody comprises:
a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 1;
a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 2;
a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 3;
a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 4;
a VL CDR2 region comprising the amino acid sequence of SEQ ID NO: 5; and a VL CDR3 region comprising the amino acid sequence of SEQ ID NO: 6.

7\. (Original) The unit dose vial of claim 6, wherein the antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 47, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 48.

8\. (Original) The unit dose vial of claim 6, wherein the antibody is solubilized in the solution such that the solution is clear, colorless, and without precipitate.

9\. (Original) A method of treating a condition in a human subject by administering the unit dose vial of claim 6, wherein the condition is primary hemophagocytic lymphohistiocytosis (HLH) or secondary HLH.

10\. (Original) The method of claim 9, wherein the human subject is pediatric or adult.

OFFICE 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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection.  Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.  Applicant's submission filed on 4-25-24 has been entered.
Reasons for Allowance
The following is an examiner’s statement of reasons for allowance:
Commonly, HLH patients are pediatric patients weighing less than 60 kg and are considered a “fragile” population due to the severity of their disease pathology (see, e.g., De Min et al. (2015),  ABSTRACT NUMBER: 3097, at 1st paragraph, and Jordan et al. (2015), Nl-0501: First Results from a Pilot Phase 2 Study in Children with Primary HLH, at pages 7-9, (both cited on an IDS).
Likewise, a form of HLH, known as macrophage activation syndrome (MAS) occurs in the context of systemic juvenile idiopathic arthritis (sJIA).
As described at page 295, left col., 1st paragraph of Ravelli et al. (2012), cited on an IDS, like the “fragile” patient population described by De Min, pediatric patients suffering from MAS in the context of sJIA are similarly at risk of death and urgently in need of rapid treatment, typically in a clinical / hospital setting:
“MAS is becoming an increasingly recognized, sometimes fatal, complication of sJIA disease flare.  Because of the urgency in making the diagnosis of MAS and instituting appropriate therapy in a timely fashion, efforts are ongoing to establish timely, practical, and highly sensitive and specific criteria for recognizing MAS in children with sJIA.” (see also the “Main clinical, laboratory and pathological features of macrophage activation syndrome” reported in Table 1 of Ravelli).
Given the knowledge in the art described above it remains this examiner’s opinion that it would not have been obvious to the ordinarily skilled artisan that an anti-IFNγ antibody, such as the NI-0501 antibody of U.S. Patent Nos. 7700098 or  9682142 (both cited on an IDS), should be formulated at high dose, e.g., to facilitate sub-cutaneous self-administration in an at home setting (see Warne et al., European Journal of Pharmaceutics and Biopharmaceutics 78 (2011) 208–212, at page 208, left col., cited on an IDS) when the primary patient population to be treated is “fragile” and therefore most likely to be receiving treatment in a clinical setting rather than at home.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion

APPLICANT REBUTTAL: REMARKS
Upon entry to these amendments, claims 1-10 are pending in the present application. In this response, claim 6 has been amended, without prejudice or disclaimer. Support for the claim amendments can be found throughout the application as originally filed. No new matter is added.
Amendment and cancellation of certain claims is not to be construed as a dedication to the public of any of the subject matter of the claims as previously presented. The above-noted amendments are supported by the application as originally filed and do not introduce any new matter. The amendments are made without prejudice to the prosecution of any canceled or amended subject matter in one or more continuing application(s).
Claim Rejections - 35 USC §112
Claims 6-10 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. Specifically, the Office alleges that the instant specification does not teach or suggest "a unit dose vial comprising...4mL.... of a fully human anti-interferon gamma (IFNy) monoclonal..."' Applicant
respectfully traverses.
Without acquiescing to the assertions of the Office and solely for the purposes of
expediting prosecution, independent claim 6 is amended to delete the reference to a unit dose vial comprising 4mL of a fully anti-interferon gamma (IFNy) monoclonal antibody. Claim 6 is amended herein to recite "A unit dose vial comprising, 2 mL, 10 mL or 20 mL of a fully human anti-interferon gamma (IFNy) monoclonal antibody..." for which the Office acknowledges to be supported by the specification as filed. 2 Accordingly, claim 6 and the remaining claims subject to the rejection which properly depend therefrom comply with the written description requirement. For at least the foregoing reasons, Applicant submits that claims 6-10 meet the
1 See Office Action at Page 4, fourth paragraph
2 See Office Action at Page 4, third paragraph
written description requirement and respectfully requests withdrawal of the rejection under 35 U.S.C. § 112.
Double Patenting
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,091,543 in view of Daugherty et al. (Advanced Drug Delivery Reviews 58 (2006) 686- 706) and Warne et al. (20060193850).
Without acquiescing to the rejection and solely in the interest of expediting prosecution, Applicant submits herewith an electronic Terminal Disclaimer over U.S. Patent 11,091,543. Withdrawal of this rejection is respectfully requested.
CONCLUSION


CITED REFERENCE SUMMARIES: Ref US7700098: Claims:
An isolated fully human monoclonal anti-IFNγ antibody or fragment thereof, wherein said antibody comprises: (a) a VH CDR1 region consisting of the amino acid sequence SYAMS (SEQ ID NO:3); (b) a VH CDR2 region consisting of the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4), (c) a VH CDR3 region consisting of the amino acid sequence DGSSGWYVPHWFDP (SEQ ID NO:5), (d) a VL CDR1 region consisting of the amino acid sequence TRSSGSIASNYVQ (SEQ ID NO:8); (e) a VL CDR2 region consisting of the amino acid sequence EDNQRPS (SEQ ID NO:9); and (f) a VL CDR3 region consisting of the amino acid sequence QSYDGSNRWM (SEQ ID NO:10); wherein said antibody or fragment thereof binds human IFNγ. 2. The antibody of claim 1, wherein said antibody is an IgG isotype. 3. The antibody of claim 1, wherein said antibody comprises the heavy chain variable amino acid sequence of SEQ ID NO: 2. 4. The antibody of claim 3, wherein said antibody comprises the light chain variable amino acid sequence of SEQ ID NO: 7. 5. An isolated fully human monoclonal antibody, wherein said antibody comprises the heavy chain variable amino acid sequence of SEQ ID NO: 2, wherein said antibody binds human IFNγ. 6. The antibody of claim 5, wherein said antibody further comprises the light chain variable amino acid of SEQ ID NO: 7, wherein said antibody binds human IFNγ. 7. The antibody of claim 5, wherein said antibody is an IgG isotype. 8. A pharmaceutical composition comprising an antibody of claim 1 and a carrier. 9. A pharmaceutical composition comprising an antibody of claim 5 and a carrier.
An isolated fully human monoclonal anti-IFNγ antibody or fragment thereof, wherein said antibody comprises: (a) a VH CDR1 region consisting of the amino acid sequence SYAMS (SEQ ID NO:3); (b) a VH CDR2 region consisting of the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4), (c) a VH CDR3 region consisting of the amino acid sequence DGSSGWYVPHWFDP (SEQ ID NO:5), (d) a VL CDR1 region consisting of the amino acid sequence TRSSGSIASNYVQ (SEQ ID NO:8); (e) a VL CDR2 region consisting of the amino acid sequence EDNQRPS (SEQ ID NO:9); and (f) a VL CDR3 region consisting of the amino acid sequence QSYDGSNRWM (SEQ ID NO:10); wherein said antibody or fragment thereof binds human IFNγ.
The antibody of claim 1, wherein said antibody is an IgG isotype.
The antibody of claim 1, wherein said antibody comprises the heavy chain variable amino acid sequence of SEQ ID NO: 2.
The antibody of claim 3, wherein said antibody comprises the light chain variable amino acid sequence of SEQ ID NO: 7.
An isolated fully human monoclonal antibody, wherein said antibody comprises the heavy chain variable amino acid sequence of SEQ ID NO: 2, wherein said antibody binds human IFNγ.
The antibody of claim 5, wherein said antibody further comprises the light chain variable amino acid of SEQ ID NO: 7, wherein said antibody binds human IFNγ.
The antibody of claim 5, wherein said antibody is an IgG isotype.
A pharmaceutical composition comprising an antibody of claim 1 and a carrier.
A pharmaceutical composition comprising an antibody of claim 5 and a carrier.
Ref US9682142: Claims:
What is claimed is: 1. An isolated fully human monoclonal anti-IFNγ antibody or fragment thereof, wherein said antibody comprises: (a) a VH CDR1 region comprising the amino acid sequence SYAMS (SEQ ID NO:3) or SNAMS (SEQ ID NO:43); (b) a VH CDR2 region comprising the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4) or TLTGSGGTAYYADSVEG (SEQ ID NO:44), (c) a VH CDR3 region comprising an amino acid sequence selected from the group consisting of DGSSGWYVPHWFDP (SEQ ID NO:5); DHSSGWYVISGMDV (SEQ ID NO:13); DLTVGGPWYYFDY (SEQ ID NO:21); DGWNALGWLES (SEQ ID NO:29); GTELVGGGLDN (SEQ ID NO:45); RSFDSGGSFEY (SEQ ID NO:64); VGSWYLEDFDI (SEQ ID NO:69); GGNYGDYFDYFDY (SEQ ID NO:76); and DFWVITSGNDY (SEQ ID NO:89), (d) a VL CDR1 region comprising an amino acid sequence selected from the group consisting of TRSSGSIASNYVQ (SEQ ID NO:8); TRSSGSIASNYVQ (SEQ ID NO:16); TRSGGSIGSYYVQ (SEQ ID NO:32); TRSSGTIASNYVQ (SEQ ID NO:39); TGSGGSIATNYVQ (SEQ ID NO:48); TGSSGSIASNYVQ (SEQ ID NO:55); TRSSGSIASNYVH (SEQ ID NO:72); TGRNGNIASNYVQ (SEQ ID NO:84); AGSSGSIASNYVQ (SEQ ID NO:97) and TRSSGSIVSNYVQ (SEQ ID NO:106); (e) a VL CDR2 region comprising an amino acid sequence selected from the group consisting of EDNQRPS (SEQ ID NO:9); EDNQRPS (SEQ ID NO:17); DDDQRPS (SEQ ID NO:25); DDKKRPS (SEQ ID NO:33); EDTQRPS (SEQ ID NO:85) and EDNRRPS (SEQ ID NO:107); and (f) a VL CDR3 region comprising an amino acid sequence selected from the group consisting of QSYDGSNRWM (SEQ ID NO:10); QSNDSDNVV (SEQ ID NO:18); QSYDSSNVV (SEQ ID NO:26); QSYDSNNLVV (SEQ ID NO:34); QSYDNSNHWV (SEQ ID NO:40); QSYDSDNHHVV (SEQ ID NO:49); QSYDSSNQEVV (SEQ ID NO:56); QSYDSNNFWV (SEQ ID NO:61); QSSDTTYHGGVV (SEQ ID NO:73); QSYEGF (SEQ ID NO:79); QSSDSNRVL (SEQ ID NO:86); QSFDSTNLVV (SEQ ID NO:92); and QSYSYNNQVV (SEQ ID NO:98), wherein said antibody binds IFNγ. 2. The antibody of claim 1, wherein said antibody is an IgG isotype. 3. An isolated fully human monoclonal antibody, wherein said antibody comprises a heavy chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 12, 20, 28, 36, 42, 51, 58, 63, 68, 75, 81, 88, 94 or 103 and a light chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 7, 15, 23, 31, 38, 47, 54, 60, 66, 71, 78, 83, 91, 96 or 105, wherein said antibody binds IFNγ. 4. A pharmaceutical composition comprising an antibody of claim 1 and a carrier. 5. A pharmaceutical composition comprising an antibody of claim 3 and a carrier. 6. A method of alleviating a symptom of an autoimmune disease or inflammatory disorder, the method comprising administering an antibody of claim 1 to a subject in need thereof in an amount sufficient to alleviate the symptom of the autoimmune disease or inflammatory disorder in the subject, wherein the autoimmune disease or inflammatory disorder is selected from the group consisting of Crohn's Disease, psoriasis, rheumatoid arthritis, and secondary progressive multiple sclerosis. 7. The method of claim 6, wherein said subject is a human. 8. The method of claim 6, wherein said antibody comprises a VH CDR1 region comprising the amino acid sequence SYAMS (SEQ ID NO:3); a VH CDR2 region comprising the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4), a VH CDR3 region comprising the amino acid sequence DGSSGWYVPHWFDP (SEQ ID NO:5); a VL CDR1 region comprising the amino acid sequence TRSSGSIASNYVQ (SEQ ID NO:8); a VL CDR2 region comprising the amino acid sequence EDNQRPS (SEQ ID NO:9); and a VL CDR3 region comprising an amino acid sequence QSYDGSNRWM (SEQ ID NO:10). 9. The method of claim 6, wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 2 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7. 10. The method of claim 6, wherein said antibody is administered intravenously.
An isolated fully human monoclonal anti-IFNγ antibody or fragment thereof, wherein said antibody comprises: (a) a VH CDR1 region comprising the amino acid sequence SYAMS (SEQ ID NO:3) or SNAMS (SEQ ID NO:43); (b) a VH CDR2 region comprising the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4) or TLTGSGGTAYYADSVEG (SEQ ID NO:44), (c) a VH CDR3 region comprising an amino acid sequence selected from the group consisting of DGSSGWYVPHWFDP (SEQ ID NO:5); DHSSGWYVISGMDV (SEQ ID NO:13); DLTVGGPWYYFDY (SEQ ID NO:21); DGWNALGWLES (SEQ ID NO:29); GTELVGGGLDN (SEQ ID NO:45); RSFDSGGSFEY (SEQ ID NO:64); VGSWYLEDFDI (SEQ ID NO:69); GGNYGDYFDYFDY (SEQ ID NO:76); and DFWVITSGNDY (SEQ ID NO:89), (d) a VL CDR1 region comprising an amino acid sequence selected from the group consisting of TRSSGSIASNYVQ (SEQ ID NO:8); TRSSGSIASNYVQ (SEQ ID NO:16); TRSGGSIGSYYVQ (SEQ ID NO:32); TRSSGTIASNYVQ (SEQ ID NO:39); TGSGGSIATNYVQ (SEQ ID NO:48); TGSSGSIASNYVQ (SEQ ID NO:55); TRSSGSIASNYVH (SEQ ID NO:72); TGRNGNIASNYVQ (SEQ ID NO:84); AGSSGSIASNYVQ (SEQ ID NO:97) and TRSSGSIVSNYVQ (SEQ ID NO:106); (e) a VL CDR2 region comprising an amino acid sequence selected from the group consisting of EDNQRPS (SEQ ID NO:9); EDNQRPS (SEQ ID NO:17); DDDQRPS (SEQ ID NO:25); DDKKRPS (SEQ ID NO:33); EDTQRPS (SEQ ID NO:85) and EDNRRPS (SEQ ID NO:107); and (f) a VL CDR3 region comprising an amino acid sequence selected from the group consisting of QSYDGSNRWM (SEQ ID NO:10); QSNDSDNVV (SEQ ID NO:18); QSYDSSNVV (SEQ ID NO:26); QSYDSNNLVV (SEQ ID NO:34); QSYDNSNHWV (SEQ ID NO:40); QSYDSDNHHVV (SEQ ID NO:49); QSYDSSNQEVV (SEQ ID NO:56); QSYDSNNFWV (SEQ ID NO:61); QSSDTTYHGGVV (SEQ ID NO:73); QSYEGF (SEQ ID NO:79); QSSDSNRVL (SEQ ID NO:86); QSFDSTNLVV (SEQ ID NO:92); and QSYSYNNQVV (SEQ ID NO:98), wherein said antibody binds IFNγ.
The antibody of claim 1, wherein said antibody is an IgG isotype.
An isolated fully human monoclonal antibody, wherein said antibody comprises a heavy chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 12, 20, 28, 36, 42, 51, 58, 63, 68, 75, 81, 88, 94 or 103 and a light chain variable amino acid sequence selected from the group consisting of SEQ ID NOS: 7, 15, 23, 31, 38, 47, 54, 60, 66, 71, 78, 83, 91, 96 or 105, wherein said antibody binds IFNγ.
A pharmaceutical composition comprising an antibody of claim 1 and a carrier.
A pharmaceutical composition comprising an antibody of claim 3 and a carrier.
A method of alleviating a symptom of an autoimmune disease or inflammatory disorder, the method comprising administering an antibody of claim 1 to a subject in need thereof in an amount sufficient to alleviate the symptom of the autoimmune disease or inflammatory disorder in the subject, wherein the autoimmune disease or inflammatory disorder is selected from the group consisting of Crohn's Disease, psoriasis, rheumatoid arthritis, and secondary progressive multiple sclerosis.
The method of claim 6, wherein said subject is a human.
The method of claim 6, wherein said antibody comprises a VH CDR1 region comprising the amino acid sequence SYAMS (SEQ ID NO:3); a VH CDR2 region comprising the amino acid sequence AISGSGGSTYYADSVKG (SEQ ID NO:4), a VH CDR3 region comprising the amino acid sequence DGSSGWYVPHWFDP (SEQ ID NO:5); a VL CDR1 region comprising the amino acid sequence TRSSGSIASNYVQ (SEQ ID NO:8); a VL CDR2 region comprising the amino acid sequence EDNQRPS (SEQ ID NO:9); and a VL CDR3 region comprising an amino acid sequence QSYDGSNRWM (SEQ ID NO:10).
The method of claim 6, wherein said antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 2 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 7.
The method of claim 6, wherein said antibody is administered intravenously.