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 .
Election/Restrictions and Claim Status
In response to Requirement for Election/Restriction mailed on 05/13/2022, applicant has elected on 11/11/2022, without traverse, Group I, including claims 1, 4, 7, 9, 12, and 28. Applicant also asserts claims 62-71 are included in the elected group, as each of these claims depends from the elected independent claims. The cancellation of claims 32—35, 40, 41, 48,49, 51, and 54-56 render the restriction moot and the restriction is dropped.
Status of Application, Amendments, and/or Claims
The response filed on 17 December, 2024 has been entered in full. The response is an amendment to a non-final rejection to the claim set filed on 11 November, 2022. In the amendment, claims 1 and 28 are amended, claims 7, 9, 12, 28, 62-71 are previously presented, claims 2-6, 8, 10, 11, 13-27, and 29-61 are cancelled, and claims 72 and 73 are new. Therefore, claims 1, 7, 9, 12, 28, and 62-73 are pending and are the subject of this Office Action.
Priority
This application is a 371 of Application No. PCT/US2017/022065 filed March 13, 2017, which claims domestic benefit to U.S. Provisional Application No. 62/307,896 filed on March 14, 2016.
Status of Objections and Rejections
In the office action of 06/17/2024
The specification was objected to for missing the incorporation by reference paragraph required for sequences by 37 CFR 1.821(c)(1). The amendment to the specification has overcome this objection.
Claim 4 was rejected under 35 U.S.C. 103 over Fox et al. in view of Ram et al. and Koura et al., and further in view of Cojocaru et al. and Fowler et al. The cancellation of the claim has rendered the rejection moot and the rejection has been withdrawn.
Claims 1, 7, 9, 12, 28, and 62-71 were rejected under 35 U.S.C. 103 over Fox et al. in view of Ram et al. and Koura et al. as evidenced by Parikh et al. The amendments to claims 1 and 28 necessitates a new 103 rejection over Fox in view of Przepiorka and Koura as evidenced by Parikh and Petrovic.
Claims 1, 12, 28, 62-64, 66, 68, and 71 were rejected under nonstatutory double patenting (NSDP) over U.S. Patent No. 11,560,434 in view of Fox et al. in view of Ram et al. and Koura et al. as evidenced by Parikh et al. The amendments to claims 1 and 28 necessitates the new NSDP rejection in view of Fox in view of Przepiorka and Koura as evidenced by Parikh and Petrovic.
Claims 1, 12, 28, 62-64, 66, 68, and 71 were rejected under nonstatutory double patenting (NSDP) over U.S. Patent No. 10,040,855 in view of Fox et al. in view of Ram et al. and Koura et al. as evidenced by Parikh et al. The amendments to claims 1 and 28 necessitates the new NSDP rejection in view of Fox in view of Przepiorka and Koura as evidenced by Parikh and Petrovic.
Claims 1, 4, 9, 12, 28, 62-67, and 69-71 were provisionally rejected under nonstatutory double patenting with US Application No. 16/084,392. The signing of a terminal disclaimer renders the rejection moot and the rejection is withdrawn.
The introduction of claims 72 and 73 necessitates the new grounds of rejection over Fox in view of Przepiorka and Koura as evidenced by Parikh and Petrovic.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7, 9, 12, 28, and 62-73 are rejected under 35 U.S.C. 103 as being unpatentable over Fox et al. (US20120282249A1) (hereafter Fox) in view of Przepiorka et al. (1996) Allogeneic Transplantation for Advanced Leukemia: Improved Short-Term Outcome With Blood Stem Cell Grafts and Tacrolimus Transplantation 62(12) 1806-1810 (hereafter Przepiorka) and Koura et al. (2013) In vivo T cell costimulation blockade with abatacept for acute graft versus host disease prevention: a first-in-disease trial. Biol Blood Marrow Transplant (19) 1638-1649 (hereafter Koura) as evidenced by Parikh et al. (2012) Vedolizumab for the treatment of acute ulcerative colitis: a randomized controlled phase 2 dose-ranging study Inflamm Bowel Dis. 18 (8) 1470-1479 (hereafter Parikh) and Petrovic et al. (2004, of record IDS 12/17/2024, NPL Cite No.28) (hereafter Petrovic).
Regarding claims 1 and 28, Fox teaches a method comprising administering to a human patient a humanized antibody having binding specificity for human α4β7 integrin, wherein the humanized antibody is administered to the patient according to the following dosing regimen: a. an initial dose of 300 mg of the humanized antibody as an intravenous infusion; b. followed by a second subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about two weeks after the initial dose; c. followed by a third subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about six weeks after the initial dose; further wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex (see paras. [0023, 0132, and 0168]). Fox also teaches that the antigen-binding region comprises the CDRs with SEQ ID NOs: 8-13 (see para. [0023 and 0132]) which are identical to SEQ ID NOs: 4-9 recited in instant claims 1 and 28. See sequence-to-sequence alignments below.
Sequence alignment of SEQ ID NO:4 of instant application with SEQ ID NO:8 of Fox et al.:
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Sequence alignment of SEQ ID NO:5 of instant application with SEQ ID NO:9 of Fox et al.:
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Sequence alignment of SEQ ID NO:6 of instant application with SEQ ID NO:10 of Fox et al.:
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Sequence alignment of SEQ ID NO:7 of instant application with SEQ ID NO:11 of Fox et al.:
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Sequence alignment of SEQ ID NO:8 of instant application with SEQ ID NO:12 of Fox et al.:
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Sequence alignment of SEQ ID NO:9 of instant application with SEQ ID NO:13 of Fox et al.:
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Fox teaches that the composition can be used to treat diseases or pathogens whose etiologies exploit the interaction of MAdCAM (e.g., MAdCAM-1) with α4β7as well as inflammatory diseases associated with mucosal tissues such as graft versus host disease (see paras. [0168, 0170, 0188]), further Fox teaches acute graft versus host disease as evidenced by Petrovic (which Fox cites) which teaches acute GVHD develops in the intestine and further α4β7 is involved in the development of acute GVHD (pg.1542, col 1, lines 8-11/ pg.1542, col 2, line 23 - pg.1543, col 1, line 1). Additionally, Fox teaches ““Treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disease as well as those in which the disease or its recurrence is to be prevented. Hence, the patient to be treated herein may have been diagnosed as having the disease or may be predisposed or susceptible to the disease.” (see para. [0088]).
Regarding claim 7, Fox teaches that the humanized antibody is reconstituted from a lyophilized formulation (see paras. [0031, 0157])
Regarding claims 9, 65 and 69-70, Fox teaches that the humanized antibody has a heavy chain variable region sequence of amino acids 20 to 140 of SEQ ID NO: 2, and/or a light chain variable region sequence of amino acids 20 to 131 of SEQ ID NO: 4 and the humanized antibody has a heavy chain comprising amino acids 20 to 470 of SEQ ID NO: 2 and a light chain comprising amino acids 20 to 238 of SEQ ID NO: 4 (see para. [0133]). SEQ ID NOs: 2 and 4 disclosed by Fox et al. are identical to SEQ ID NOs: 1 and 2 recited in the instant application respectively. See sequence-to-sequence alignments below.
Sequence alignment of SEQ ID NO: 1 of instant application with SEQ ID NO: 2 of Fox et al.:
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Sequence alignment of SEQ ID NO: 2 of instant application with SEQ ID NO: 4 of Fox et al.:
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Regarding claims 12 and 71, Fox et al. teach that the humanized antibody is vedolizumab (see para. [0135] and Fig. 2).
Regarding claim 64, Fox teaches that the humanized antibody is administered to the patient over about 30 minutes (see para. [0030]).
Fox fails to teach the use of the antibody before and after allo-HSCT, the initial dose of the antibody is administered the day before allo-HSCT, the administration of a calcineurin inhibitor before allo-HSCT followed by continued administration 100 days, the administration of methotrexate after the allo-HSCT, and the engraftment of HSCs of claims 1 and 28. Further Fox fails to teach the calcineurin inhibitor being tacrolimus of claims 72 and 73.
Koura, however, teaches a method for improved prevention of acute GVHD during unrelated-donor hematopoietic cell transplantation in which the initial dose of the drug abatacept (a modified antibody which inhibits CD28:CD80/86 costimulation) is administered on the day before transplantation (see Abstract). Koura also teaches abatacept works by blocking T cell proliferation a mechanism similar to antibodies against α4β7 (pg.1642, col 2, lines 2-10) and that early inhibition of alloproliferation to limit the mortality of early GVHD after HLA-mismatched HCT is supported by literature (pg.1648, col 1, lines 36-39).
Koura fails to teach the administration of a calcineurin inhibitor before allo-HSCT followed by continued administration 100 days after the allo-HSCT, and the administration of methotrexate after the allo-HSCT, and the engraftment of HSCs of claims 1 and 28. Koura further fails to teach the calcineurin inhibitor being tacrolimus of claims 72 and 73.
Przepiorka, however, in regards to claims 1 and 28 teaches the administration of a calcineurin inhibitor prior to allogeneic bone marrow transplant followed by continued administration for 180 days after transplantation and further the administration of methotrexate on days 1 3, 6, and 11 after transplant to prevent the development of GVHD (pg.3, lines 27-31). It is noted that although the continued administration of the calcineurin is longer then the claimed 100 days, Figure 1 of the Przepiorka highlights that there is still significant affect from the combination of a calcineurin inhibitor with methotrexate at day 100 on actuarial survival (Figure 1, dotted line). Further Przepiorka teaches that the treatment during treatment must support engraftment and prophylaxis to prevent GVHD, and further teaches that tacrolimus does not significantly impair engraftment (pg.3, section Assessment of engraftment/pg.5, line 24).
In regards to claims 72 and 73 Przepiorka teaches the use of the calcineurin inhibitor tacrolimus and teaches that tacrolimus has been more effective than other calcineurin inhibitors such as cyclosporin (Abstract/pg.5 line 15).
Regarding claims 62, 63 and 66-68, since Fox, Koura, and Przepiorka teach the method of independent claims 1 and 28, they also necessarily teach claims 62, 63 and 66-68 which merely recite the intended results of the independent claims. Additionally, regarding claim 63, it is well known in the art that the mean elimination half-life of vedolizumab is 15–22 days across the dose range tested (see Parikh et al. Page 1473 Pharmacokinetics). Therefore, it can reasonably be expected that the initial 300 mg dose administered the day before hematopoietic stem cell infusion will sustain α4β7 blockade at the time of infusion.
Thus, discloses a method comprising administering to a patient a humanized antibody having binding specificity for human α4β7 integrin, wherein administration comprises three subsequent 300mg intravenous infusions, and further wherein the antibody has the same binding region of the claimed antibody. Fox further highlights that this method can be used to prevent or treat acute GVHD. Koura teaches an initial dose of an antibody to prevent GVHD before transplantation to inhibit early alloproliferation, and Przepiorka teaches the administration of tacrolimus before and after transplantation and the administration of methotrexate after transplantation to support GVHD prophylaxis, further Przepiorka teaches engraftment is essential for prevention of GVHD and highlights that tacrolimus has no impairment on the process. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Fox, Koura, and Przepiorka with a reasonable expectation of success to modify the administration protocol of Fox by delivering a dose of the antibody before transplantation to prevent early alloproliferation, and to co-administer tacrolimus and methotrexate to support prophylaxis, to develop a more effective method to prevent or treat GVHD during allo-HSCT.
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, 12, 28, 62-64, 66, 68 and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 10 and 13 of U.S. Patent No. US11560434B2 (patent ‘434) in view of Fox et al., Koura et al., and Przepiorka et al. as evidenced by Parikh et al. and Petrovic et al.
Regarding instant claims 1 and 28, claim 1 of the patent ‘434 teaches an anti-α4β7 antibody comprising CDRs of SEQ ID NOs: 8-13, which are identical to SEQ ID NOs: 4-9 in instant application (see patent ‘434 claims 1 and 10). See sequence-to-sequence alignments below.
Sequence alignment of SEQ ID NO:4 of instant application with SEQ ID NO:8 of patent ‘434:
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Sequence alignment of SEQ ID NO:5 of instant application with SEQ ID NO:9 of patent ‘434:
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Sequence alignment of SEQ ID NO:6 of instant application with SEQ ID NO:10 of patent ‘434:
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Sequence alignment of SEQ ID NO:7 of instant application with SEQ ID NO:11 of patent ‘434:
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Sequence alignment of SEQ ID NO:8 of instant application with SEQ ID NO:12 of patent ‘434:
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Sequence alignment of SEQ ID NO:9 of instant application with SEQ ID NO:13 of patent ‘434:
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Because the claims of patent ‘434 are drawn to an antibody but do not recite a use for the antibody, the claims are construed using the reference patent disclosure to help determine obviousness. The specification of patent ‘434 teaches a method comprising administering to a human patient a humanized antibody having binding specificity for human α4β7 integrin, wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin (see col. 4 lines 15-24). Patent ‘434 teaches that the composition can be used to treat graft versus host disease (see col. 32 lines 30-37).
Patent ‘434 does not teach a method of preventing acute GVHD, the dosing regimen for the antibody, the initial dose of the antibody being administered before transplantation and further the administering of a calcineurin inhibitor before and for 100 days after transplantation, as well as administration of methotrexate after transplantation. Patent ‘434 also does not teach engraftment of HSCs to prevent GVHD.
Fox teaches a method comprising administering to a human patient a humanized antibody having binding specificity for human α4β7 integrin, wherein the humanized antibody is administered to the patient according to the following dosing regimen: a. an initial dose of 300 mg of the humanized antibody as an intravenous infusion; b. followed by a second subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about two weeks after the initial dose; c. followed by a third subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about six weeks after the initial dose; further wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex (see paras. [0023, 0132, and 0168]).
Fox also teaches that the composition can be used to treat diseases or pathogens whose etiologies exploit the interaction of MAdCAM (e.g., MAdCAM-1) with α4β7as well as inflammatory diseases associated with mucosal tissues such as graft versus host disease (see paras. [0168, 0170, 0188]). Additionally, Fox teaches ““Treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disease as well as those in which the disease or its recurrence is to be prevented. Hence, the patient to be treated herein may have been diagnosed as having the disease or may be predisposed or susceptible to the disease.” (see para. [0088]).
Fox fails to teach the use of the antibody before and after allo-HSCT, the initial dose of the antibody is administered the day before allo-HSCT, the administration of a calcineurin inhibitor before allo-HSCT followed by continued administration 100 days, the administration of methotrexate after the allo-HSCT, and the engraftment of HSCs of claims 1 and 28. Further Fox fails to teach the calcineurin inhibitor being tacrolimus of claims 72 and 73.
Koura, however, teaches a method for improved prevention of acute GVHD during unrelated-donor hematopoietic cell transplantation in which the initial dose of the drug abatacept (a modified antibody which inhibits CD28:CD80/86 costimulation) is administered on the day before transplantation (see Abstract). Koura also teaches abatacept works by blocking T cell proliferation a mechanism similar to antibodies against α4β7 (pg.1642, col 2, lines 2-10) and that early inhibition of alloproliferation to limit the mortality of early GVHD after HLA-mismatched HCT is supported by literature (pg.1648, col 1, lines 36-39).
Koura fails to teach the administration of a calcineurin inhibitor before allo-HSCT followed by continued administration 100 days after the allo-HSCT, and the administration of methotrexate after the allo-HSCT, and the engraftment of HSCs of claims 1 and 28. Koura further fails to teach the calcineurin inhibitor being tacrolimus of claims 72 and 73.
Przepiorka, however, in regards to claims 1 and 28 teaches the administration of a calcineurin inhibitor prior to allogeneic bone marrow transplant followed by continued administration for 180 days after transplantation and further the administration of methotrexate on days 1 3, 6, and 11 after transplant to prevent the development of GVHD (pg.3, lines 27-31). It is noted that although the continued administration of the calcineurin is longer then the claimed 100 days, Figure 1 of the Przepiorka highlights that there is still significant affect from the combination of a calcineurin inhibitor with methotrexate at day 100 on actuarial survival (Figure 1, dotted line). Further Przepiorka teaches that the treatment during treatment must support engraftment and prophylaxis to prevent GVHD, and further teaches that tacrolimus does not significantly impair engraftment (pg.3, section Assessment of engraftment/pg.5, line 24).
Thus, Fox discloses a method comprising administering to a patient a humanized antibody having binding specificity for human α4β7 integrin, wherein administration comprises three subsequent 300mg intravenous infusions, and further wherein the antibody has the same binding region of the claimed antibody. Fox further highlights that this method can be used to prevent or treat acute GVHD. Koura teaches an initial dose of an antibody to prevent GVHD before transplantation to inhibit early alloproliferation, and Przepiorka teaches the administration of tacrolimus before and after transplantation and the administration of methotrexate after transplantation to support GVHD prophylaxis, further Przepiorka teaches engraftment is essential for prevention of GVHD and highlights that tacrolimus has no impairment on the process. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention in possession of patent ‘434 would have found it obvious to combine the teachings of Fox, Koura, and Przepiorka with a reasonable expectation of success to use the antibody against α4β7 of the patent with the administration protocol of Fox modified by delivering a dose of the antibody before transplantation to prevent early alloproliferation, and to co-administer tacrolimus and methotrexate to support prophylaxis, to develop a more effective method to prevent or treat GVHD during allo-HSCT.
Regarding instant claims 12 and 71, patent ‘434 teaches that the humanized antibody is vedolizumab (see claims 6 and 13).
Regarding instant claims 62, 63 and 66-68, since patent ‘434, Fox et al., Koura et al., and Przepiorka et al. teach the method of independent claims 1 and 28, they also necessarily teach claims 62, 63 and 66-68 which merely recite the intended results of the independent claims. Additionally, regarding claim 63, it is well known in the art that the mean elimination half-life of vedolizumab is 15–22 days across the dose range tested (see Parikh et al. Page 1473 Pharmacokinetics). Therefore, it can reasonably be expected that the initial 300 mg dose administered the day before hematopoietic stem cell infusion will sustain α4β7 blockade at the time of infusion.
Regarding instant claim 64, patent ‘434 fails to teach the antibody administered to the patient over 30 minutes, however, Fox teaches that the humanized antibody is administered to the patient over about 30 minutes (see para. [0030]).
Claims 1, 12, 28, 62-64, 66, 68 and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-8, 16 and 18 of U.S. Patent No. US10040855B2 (patent ‘855) in view of Fox et al., Koura et al., and Przepiorka et al. as evidenced by Parikh et al. and Petrovic et al.
Regarding instant claims 1 and 28, patent ‘855 teaches an anti-α4β7 antibody comprising CDRs of SEQ ID NOs: 8-13, which are identical to SEQ ID NOs: 4-9 in instant application (see patent ‘855 claims 1, 6 and 16). See sequence-to-sequence alignments below.
Sequence alignment of SEQ ID NO:4 of instant application with SEQ ID NO:8 of patent ‘855:
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Sequence alignment of SEQ ID NO:5 of instant application with SEQ ID NO:9 of patent ‘855:
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Sequence alignment of SEQ ID NO:6 of instant application with SEQ ID NO:10 of patent ‘855:
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Sequence alignment of SEQ ID NO:7 of instant application with SEQ ID NO:11 of patent ‘855:
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Sequence alignment of SEQ ID NO:8 of instant application with SEQ ID NO:12 of patent ‘855:
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Sequence alignment of SEQ ID NO:9 of instant application with SEQ ID NO:13 of patent ‘855:
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Because the claims of patent ‘855 are drawn to an antibody but do not recite a use for the antibody, the claims are construed using the reference patent disclosure to help determine obviousness. The specification of patent ‘855 teaches a method comprising administering to a human patient a humanized antibody having binding specificity for human α4β7 integrin wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin (see col.4 lines 9-18). Patent ‘855 teaches that the composition can be used to treat graft versus host disease (see col. 32 lines 23-30).
Patent ‘855 does not teach a method of preventing acute GVHD, the dosing regimen for the antibody, the initial dose of the antibody being administered before transplantation and further the administering of a calcineurin inhibitor before and for 100 days after transplantation, as well as administration of methotrexate after transplantation. Patent ‘434 also does not teach engraftment of HSCs to prevent GVHD.
Fox et al. teach a method comprising administering to a human patient a humanized antibody having binding specificity for human α4β7 integrin, wherein the humanized antibody is administered to the patient according to the following dosing regimen: a. an initial dose of 300 mg of the humanized antibody as an intravenous infusion; b. followed by a second subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about two weeks after the initial dose; c. followed by a third subsequent dose of 300 mg of the humanized antibody as an intravenous infusion at about six weeks after the initial dose; further wherein the humanized antibody comprises an antigen binding region of nonhuman origin and at least a portion of an antibody of human origin, wherein the humanized antibody has binding specificity for the α4β7 complex (see paras. [0023, 0132, and 0168]).
Fox et al. also teach that the composition can be used to treat diseases or pathogens whose etiologies exploit the interaction of MAdCAM (e.g., MAdCAM-1) with α4β7as well as inflammatory diseases associated with mucosal tissues such as graft versus host disease (see paras. [0168, 0170, 0188]). Additionally, Fox et al. teach ““Treatment” refers to both therapeutic treatment and prophylactic or preventative measures. Those in need of treatment include those already with the disease as well as those in which the disease or its recurrence is to be prevented. Hence, the patient to be treated herein may have been diagnosed as having the disease or may be predisposed or susceptible to the disease.” (see para. [0088]).
Fox fails to teach the use of the antibody before and after allo-HSCT, the initial dose of the antibody is administered the day before allo-HSCT, the administration of a calcineurin inhibitor before allo-HSCT followed by continued administration 100 days, the administration of methotrexate after the allo-HSCT, and the engraftment of HSCs of claims 1 and 28. Further Fox fails to teach the calcineurin inhibitor being tacrolimus of claims 72 and 73.
Koura, however, teaches a method for improved prevention of acute GVHD during unrelated-donor hematopoietic cell transplantation in which the initial dose of the drug abatacept (a modified antibody which inhibits CD28:CD80/86 costimulation) is administered on the day before transplantation (see Abstract). Koura also teaches abatacept works by blocking T cell proliferation a mechanism similar to antibodies against α4β7 (pg.1642, col 2, lines 2-10) and that early inhibition of alloproliferation to limit the mortality of early GVHD after HLA-mismatched HCT is supported by literature (pg.1648, col 1, lines 36-39).
Koura fails to teach the administration of a calcineurin inhibitor before allo-HSCT followed by continued administration 100 days after the allo-HSCT, and the administration of methotrexate after the allo-HSCT, and the engraftment of HSCs of claims 1 and 28. Koura further fails to teach the calcineurin inhibitor being tacrolimus of claims 72 and 73.
Przepiorka, however, in regards to claims 1 and 28 teaches the administration of a calcineurin inhibitor prior to allogeneic bone marrow transplant followed by continued administration for 180 days after transplantation and further the administration of methotrexate on days 1 3, 6, and 11 after transplant to prevent the development of GVHD (pg.3, lines 27-31). It is noted that although the continued administration of the calcineurin is longer then the claimed 100 days, Figure 1 of the Przepiorka highlights that there is still significant affect from the combination of a calcineurin inhibitor with methotrexate at day 100 on actuarial survival (Figure 1, dotted line). Further Przepiorka teaches that the treatment during treatment must support engraftment and prophylaxis to prevent GVHD, and further teaches that tacrolimus does not significantly impair engraftment (pg.3, section Assessment of engraftment/pg.5, line 24).
Thus, Fox discloses a method comprising administering to a patient a humanized antibody having binding specificity for human α4β7 integrin, wherein administration comprises three subsequent 300mg intravenous infusions, and further wherein the antibody has the same binding region of the claimed antibody. Fox further highlights that this method can be used to prevent or treat acute GVHD. Koura teaches an initial dose of an antibody to prevent GVHD before transplantation to inhibit early alloproliferation, and Przepiorka teaches the administration of tacrolimus before and after transplantation and the administration of methotrexate after transplantation to support GVHD prophylaxis, further Przepiorka teaches engraftment is essential for prevention of GVHD and highlights that tacrolimus has no impairment on the process. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention in possession of patent ‘434 would have found it obvious to combine the teachings of Fox, Koura, and Przepiorka with a reasonable expectation of success to use the antibody against α4β7 of the patent with the administration protocol of Fox modified by delivering a dose of the antibody before transplantation to prevent early alloproliferation, and to co-administer tacrolimus and methotrexate to support prophylaxis, to develop a more effective method to prevent or treat GVHD during allo-HSCT.
Regarding instant claims 12 and 71, patent ‘855 teaches that the humanized antibody is vedolizumab (see claims 7, 8 and 18).
Regarding instant claims 62, 63 and 66-68, since patent ‘855, Fox et al., Ram et al. and Koura et al. teach the method of independent claims 1 and 28, they also necessarily teach claims 62, 63 and 66-68 which merely recite the intended results of the independent claims. Additionally, regarding claim 63, it is well known in the art that the mean elimination half-life of vedolizumab is 15–22 days across the dose range tested (see Parikh et al. Page 1473 Pharmacokinetics). Therefore, it can reasonably be expected that the initial 300 mg dose administered the day before hematopoietic stem cell infusion will sustain α4β7 blockade at the time of infusion.
Regarding instant claim 64, patent ‘855 fails to teach the antibody administered to the patient over 30 minutes, however, Fox teaches that the humanized antibody is administered to the patient over about 30 minutes (see para. [0030]).
Response to Arguments
Applicant's arguments filed 12/17/2024 have been fully considered but they are not persuasive.
Applicants’ argument that “Fox et al. does not teach or suggest acute GvHD” (remarks (12/17/2024), pg.11, lines 28-29) is moot in view of the new rejection necessitated by the amendment of claims 1 and 28. Applicants’ arguments in regards to references Cojocaru et al. and Fowler et al. (Remarks (12/17/2024) pgs.13-14. Are moot in view of the cancellation of claim 4.
In response to applicant's argument that the Ram et al. “teaches away from using agents to target T cells” (Remarks (12/17/2024), pg.12, lines 21-22) due to its failure to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. prevention of GvHD by blocking the initial trafficking of T cells to secondary lymphoid organs (Remarks (12/17/2024), pg.12, lines 13-15) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further, the argument is moot in view of the new ground of rejection necessitated by the amendment to claims 1 and 28, which does not rely on Ram et al.
In response to applicant's argument “there is no teaching or suggestion in Koura et al. that the teachings therein are relevant to any other antibody let alone anti- α4β7” (Remarks (12/17/2024, pg.13, lines 2-4). The argument is against the reference 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). Koura while teaching the use of a different antibody, it is used to teach administration of an antibody before transplantation, while Fox teaches the effectiveness of the antibody against α4β7 for in the use of preventing GvHD, the reason to combine does not lie in mechanism of the antibodies but instead in the obviousness to try prior administration for the treatment of the same disease. For the purpose of clarity, further explanation of the connection between references and their combination is outlined above.
In response to applicants’ argument “the formulation claims of US11560434, alone or in combination with the cited secondary art, are not suggestive of a method of preventing GVHD, evidenced by the Patent Office’s restriction of claims to the two inventions” (remarks (12/17/2024), pg. 15, lines 11-13) and “the formulation claim of US10040855 are not suggestive of a method of preventing GVHD, alone or in combination with the secondary art, evidenced by the Patent Office’s restriction of claims to the two inventions” (remarks (12/17/2024), pg. 16, lines 7-9).
Restriction is the practice of requiring an applicant to elect a single claimed invention (e.g., a combination or sub combination invention, a product or process invention, a species within a genus) for examination when two or more independent inventions and/or two or more distinct inventions are claimed in an application, (See MPEP 802.02) and is determined on an application by application basis. Further nonstatutory double patenting is only prohibited if the applications or patents are related to the instant application and the instant application is a divisional in response to a requirement for restriction (See MPEP 804.01). Since restriction of an application can be drawn to distinct inventions (defined as related inventions not connected in at least one of design, operation, or effect (e.g., can be made by, or used in, a materially different process) and wherein at least one invention is PATENTABLE (novel and nonobvious) see MPEP 802.01(II)) as is the case for U.S. patents 11560434 and 10040855. Due to the relation of the patents and the instant application and because the instant application is not related to and/or a divisional of the patents, the restrictions of the patents are not indicative of non-obviousness nor overcomes obviousness in light of secondary references.
Conclusion
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.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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