DETAILED ACTION
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 amendment and remarks, filed 5/18/26, are acknowledged.
Claims 16-21, 26-28 have been amended.
Claims 16-21, 23-31 are pending.
Claims 28-31 are withdrawn from further consideration pursuant to 37 CFR 1.14209 as being drawn to a nonelected invention.
Claims 16-21 and 23-27 are under examination.
Claims 16 is objected to for the following informalities: The claim recites administration after or before “that” the recipient has received or receives the transplant. Correction is required, for example, to recite before or after “the recipient has received the transplant”.
Applicant indicates that the amendment has overcome the objection, however,
the claims still recites “after that the” in lines 7, 9, 10 and 12.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16-21 and 23-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The scope of the method of claim 16 is unclear and indefinite. Given the formatting of amended Claim 16, it is unclear whether the “wherein” limitations recited in the last 5 lines of the claim are meant to be part of only option d), or whether they are required elements for the claim that are recited in addition to at least one of options a)-d). It is also unclear whether the claim would require administering the same antibody in each of the recited administration step. This is because the claim recites several administration steps and also several functions for the antibody in different parts of the claimed method. For example, in lines 4-5, the wherein clause specifies that “the anti-CCR7 antibody effects at least one of killing and induction of apoptosis”. However, in the last wherein clause, the claim recites that the anti-CCR7 antibody “inhibits CCR7-dependent signaling, CCR7 dependent functions, and/or CCR7 receptor internalization”.
The following is suggested clam wording to overcome the rejection:
A method for preventing or treating Graft Versus Host Disease (GVHD) in a recipient of a transplant comprising a donor cell, the method comprising administering to the recipient an anti-CCR7 antibody,
wherein the anti-CCR7 antibody effects at least one of killing and induction of apoptosis of CCR7 expressing cells in the recipient and the anti-CCR7 antibody inhibits CCR7-dependent intracellular signaling, CCR7-dependent functions, and/or CCR7 receptor internalization by at least one CCR7 ligand selected from CCL19 and CCL21;
wherein at least one administration to the recipient of the anti-CCR7 antibody is separate from the transplant, and
wherein the method comprises at least one of:
a) administration of the anti-CCR7 antibody to the recipient after the recipient has received the transplant comprising the donor cell, and before that the recipient shows symptoms of GVHD or before that the recipient has been diagnosed with GVHD;
b) administration of the anti-CCR7 antibody to the recipient after the recipient has received the transplant comprising the donor cell, and after that the recipient shows symptoms of GVHD or after the recipient has been diagnosed with GVHD;
c) administration of the anti-CCR7 antibody to the recipient of a transplant comprising the donor cell, which transplant has been prepared prior to transplantation by an ex vivo incubation with the anti-CCR7 antibody or antigen-binding fragment thereof; and,
d) administration of the anti-CCR7 antibody to the recipient after recurrence of GVHD.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 16-20 and 27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2013184200 (of record).
WO 2013184200 teaches a method of suppressing GVHD after bone marrow transplantation in a patient (i.e. in a recipient of a donor cell) comprising administering to the patient an anti-CCR7 neutralizing human antibody after transplantation (See page 23, in particular). WO 2013184200 teaches that the neutralizing antibodies act as antagonist and not agonist, and that they inhibit binding of CCL19 and CCL21 to CCR7 and inhibit CCR7 signaling (see page 16 and 21, in particular). WO 2013184200 teaches that the antibodies have a Kd of about 1 nM to about 100 nM, thus, meeting the limitations s of claims 17 and 19 (see page 16, in particular). WO 2013184200 teaches that CCL19 induced CCR7 activation protects cells from apoptosis, and that CCR7 blockage by the antibody decreases cell viability ( see page 24, in particular). See also page 20, wherein the reference teaches that apoptosis is CCR7 dependent property. Thus, neutralizing CCR7 activity would inherently also effect killing or apoptosis induction of CCR7 expressing cells, such as CCR7 expressing leukemia cells, thus meeting the limitations of the present claims. WO 2013184200 teaches that the method allows for regeneration of adaptive immunity, and breaks immune tolerance to cancer, thereby treating cancer, while maintaining GVL (see page 26, in particular).
WO 2013184200 explicitly teaches administration of the antibody after transplant and doing so would necessarily require that the antibody would be administered either before or after GVHD onset, thus meeting the limitation of either a) or b). Treatment after transplant as taught by WO 2013184200, also necessarily means that the antibody is administered separate from the transplant.
WO 2013184200 also teaches further administering the CCR7 antibody as an ADC to deplete CCR7 cells, prior to transplant (See page 23-24 and 26), which would also meet the limitation of claim 16 that recites administering to the recipient the anti-CCR7 antibody, wherein the antibody effects killing and induction of apoptosis.
Applicant’s arguments filed 5/18/26 have been fully considered, but they are not persuasive.
Applicant argues that although WO 2013184200 teaches administration of the antibody after bone marrow transplantation, it does not specifically distinguish between before GVHD or after GVHD symptoms/diagnosis as recited in parts a) and b) of claim 16.
Parts a) and b) of the claim encompass every time period after bone marrow transplantation, since administration after bone marrow transplantation would necessarily be either before onset of symptoms/diagnosis or after onset of symptoms/diagnosis. In other words, the prior art teaches administration after transplantation, and administration at any point after transplantation would necessarily meet either part a) or part b) of the claim.
Applicant further argues that WO 2013184200 does not teach administration separate from the transplant. Administration of the antibody after the transplant would necessarily mean that it is given separate from the transplant. In other words, if they are given at different times (one after the other), they are necessarily “separate”.
Applicant further argues that WO 2013184200 only teaches that CCR7 blockade decreases cell viability, and this does not necessarily mean that the antibody effects at least one of killing and induction of apoptosis of CCR7 expressing cells.
Decreasing cell viability means that the cells have died as a result of the antibody blockade. The prior art antibodies block CCR7 signals that are necessary for viability and survival of the cells, leading to their death. In other words, the antibody deprives the cells of their viability and hence “kills” them. WO 2013184200 also teaches the anti-CCR7 antibodies block CCR7 anti-apoptotic pathways and produce apoptosis (See page 25, lines 13-20, in particular).
WO 2013184200 also teaches further administering the CCR7 antibody as an ADC to deplete CCR7 cells, prior to transplant (See page 23-24 and 26), which would also meet the limitation of claim 16 that recites administering to the recipient the anti-CCR7 antibody, wherein the antibody effects killing and induction of apoptosis.
Claim(s) 16-21 and 23-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2017025569 (of record), in view of WO 2013184200 (of record), and Coghill, 2010 (of record).
WO2017025569 teaches anti-CCR7 antibodies for use in treating conditions and complications arising from tissue or organ transplantation (see page 1-5 and 36, in particular). WO2017025569 teaches that the antibodies are humanized antibodies having the HVRs of SEQ ID NO: 1 and 2, which are identical to SEQ ID NO: 1 and 2 of the instant application (see page 3 and the claims in particular). WO2017025569 teaches that said antibodies have a Kd that is not more than a factor of 10 higher than the kD of a mouse anti-CCR7 antibody having a VH of SEQ ID NO: 1 and a VL of SEQ ID NO: 2 (See the claims and page 21-22, in particular). WO2017025569 teaches that said antibodies have an IC50 of no more than 100 nM for inhibiting at least one of CCR7 dependent intracellular signaling and CCR7 receptor internalization (see page 21-22 and the claims in particular). WO2017025569 teaches that the antibodies can deplete and kill CCR7 expressing cells and that the antibodies inhibit intracellular signaling without substantial agonist effects ( see page 5, 22, and 28 in particular). WO2017025569 also teaches a method of treating cancers, such as hematological malignances, with the anti-CCR7 antibodies, and that the anti-CCR7 treatment can be combined with bone marrow or peripheral blood stem cell transplant subsequent to treatment with anti-CCR7 antibody (i.e. a transplant comprise hematopoietic stem cells, see page 37, in particular).
The reference differs from the claimed invention in that it does not explicitly teach treating GVHD or an administration regimen as set forth in (a)-(d).
WO 2013184200 teaches anti-CCR7 antibodies are useful for suppressing GVHD after bone marrow transplantation (i.e. a donor hematopoietic stem or progenitor cell transplant). WO 2013184200 teaches administering anti-CCR7 antibodies to the recipient prior to and subsequent to transplantation (see page 23, in particular). WO 2013184200 explains that said antibodies provide an anti-GVHD effect while maintain GVL effects (See page 26, in particular).
Coghill teaches that GVHD is the greatest complication limiting the clinical utility of allogeneic (i.e. donor) HSCT. Coghill teach that inhibition of CCR7 in the early post-transplantation period may represent a feasible new therapeutic approach for GVHD attenuation without compromising GVL responses.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to treat GVHD, as taught by WO 2013184200 and Cogill, as the complication of transplantation taught in the method taught by WO2017025569 . The ordinary artisan would be motivated to do so with a reasonable expectation of success, since WO 2013184200 and Coghill teaches anti-CCR7 antibodies are useful for suppressing GVHD when given after bone marrow transplantation. The timeframe of administration after transplantation but before GVHD would be obvious, since Coghill teaches the importance of CCR7 inhibition in the early transplant period. In addition, it would be obvious to maintain CCR7 administration immediately after transplantation, or in the event GVHD develops in order to suppress GVHD, since WO 2013184200 teaches anti-CCR7 antibodies are useful for suppressing GVHD after bone marrow transplantation and that patients receiving a transplant should be maintained on anti-CCR7 antibody treatments to suppress GVHD.
Applicant’s arguments filed 5/18/26 have been fully considered, but they are not persuasive.
Applicant argues that while the references teach general post-transplant administration, they do not teach the specific timing of administration before symptoms/diagnosis or after symptoms/diagnosis, as recited in parts a) or b) of the present claims.
This is not persuasive for the same reason set forth above, i.e. administration at any time after transplantation would be encompassed by the present claims, since any post-transplant administration would necessarily be either before onset of GVHD symptoms/diagnosis or after onset of GVHD symptoms/diagnosis. Regardless, the timeframe of administration after transplantation but before GVHD symptom onset/diagnosis would be obvious, since Coghill teaches the importance of CCR7 inhibition in the early transplant period. In addition, it would be obvious to maintain CCR7 administration immediately after transplantation, or in the event GVHD develops in order to suppress GVHD, since WO 2013184200 teaches anti-CCR7 antibodies are useful for suppressing GVHD after bone marrow transplantation and that patients receiving a transplant should be maintained on anti-CCR7 antibody treatments to suppress GVHD.
Applicant further argues that there would be no motivation to treat GVHD since WO 2017025569 teaches anti-CCR7 antibodies for treating conditions and complications arising from tissue transplantation, but focuses primarily on cancer treatment rather than GVHD prevention or treatment.
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).
WO 2013184200 teaches anti-CCR7 antibodies are useful for suppressing GVHD after bone marrow transplantation (i.e. a donor hematopoietic stem or progenitor cell transplant). Coghill teaches that GVHD is the greatest complication limiting the clinical utility of allogeneic (i.e. donor) HSCT. Coghill teach that inhibition of CCR7 in the early post-transplantation period may represent a feasible new therapeutic approach for GVHD attenuation without compromising GVL responses.
Applicant further argues that the present invention provides unexpected results in that it treats GVHD while maintaining GVL effects.
This was an expected benefit of using anti-CCR7 for treating GVHD. WO 2013184200 teaches that anti-CCR7 provides an anti-GVHD effect while maintain GVL effects (See page 26, in particular). Coghill teach that inhibition of CCR7 in the early post-transplantation period may represent a feasible new therapeutic approach for GVHD attenuation without compromising GVL responses.
Claim(s) 16-21 and 23-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over 8,066,996, in view of WO2017025569, WO 2013184200 and Coghill, 2010 (of record).
The ‘996 patent teaches a method for treating a subject with leukemia comprising administering to a subject an antibody that binds to CCR7 (see column 20, in particular). The ‘996 patent teaches that the anti-CCR7 treatment can be performed prior to bone marrow stem cell transplant (i.e. a transplant comprise hematopoietic stem cells, see column 21, in particular). The ‘996 patent teaches that the CCR7 antibodies kill CCR7 expressing cells.
Although the ‘996 patent does not specifically claim treating GVHD, or the antibodies having HVRs of SEQ ID NO: 1 and 2, it would be obvious to do so based on the teachings of WO 2013184200, Coghill, and WO2017025569 (see the teachings of the cited references as set forth above).
It would have been obvious to further administering the CCR7 antibody post-transplant to treat GVHD as taught by WO 2013184200 and Coghill for the same reasons set forth above..
Additionally, it would also be obvious to use the CCR7 antibodies disclosed by WO2017025569, as the CCR7 antibodies for use in the treatment methods made obvious above. The ordinary artisan would be motivated to do so with a reasonable expectation of success, since WO2017025569 teaches that they represent improved anti-CCR7 antibodies useful in human therapy to treat cancer, inflammatory conditions, and conditions or complications arising from tissue or organ transplantation (See abstract and page 2, in particular).
Applicant’s arguments filed 5/18/26 have been fully considered, but they are not persuasive.
Applicant argues that the claims are not obvious for the same reasons set forth above.
The claims stand rejected for the reasons set forth above.
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 16-21 and 23-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 8,066,996 in view of WO 2013184200, Coghill, 2010 and WO2017025569.
The ‘996 claims a method for treating a subject with a tumoral conditions comprising administering to a subject an antibody that binds to CCR7 receptor in and is effector for killing tumor cells expressing a CCR7 receptor. The ‘996 patent claims that the tumoral condition is leukemia.
Although the ‘996 patent does not specifically claim performing a bone marrow transplant and treating GVHD, it would be obvious to do so based on the teachings of WO 2013184200, Coghill, 2010, for the same reasons set forth above.
Additionally, it would also be obvious to use the CCR7 antibodies disclosed by WO2017025569, as the CCR7 antibodies for use in the treatment methods. The ordinary artisan would be motivated to do so with a reasonable expectation of success, since WO2017025569 teaches that they represent improved anti-CCR7 antibodies useful in human therapy to treat cancer, inflammatory conditions, and conditions or complications arising from tissue or organ transplantation (See abstract and page 2, in particular).
Claims 16-21 and 23-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16, 18-25, 27-31 of copending Application No. 17,767,096 in view of WO 2013184200, and, Coghill, 2010.
The ‘096 application claims an anti-CCR7 antibody for use in treating a hematological disorder, such as leukemia. The ‘096 application claims that the antibody can inhibit CCR7 intracellular signaling without substantial agonist effects, has Kd identical to that of the instant claims, and comprises HVRs of SEQ ID NO: 1 and 2, which are identical to SEQ ID NO: 1 and 2 of the instant application. The property of inducing apoptosis would also be an inherent property of the antibody, which is identical to that of the instant claims.
It would be obvious use the antibody during bone marrow transplant during treatment of said leukemia, and also to treat GVHD based on the teachings of WO 2013184200 and Coghill, 2010, for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection.
Applicant’s statement that the rejection be held in abeyance until the time of allowance is acknowledged.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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