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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 9/8/25 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/8/25 has been entered.
Claim 16 has been amended.
Claims 16-21 and 23-31 are pending.
Claims 28-31 stand withdrawn from further consideration pursuant to 37 CFR 1.14209 as being drawn to a nonelected invention.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.
In view of Applicant’s amendments, the previous grounds of rejection are withdrawn. The following are new grounds of rejection. Applicant’s arguments relevant to the new grounds of rejection will be addressed below.
Claims 16 and 27 re objected to for the following informalities: The claims recite administration after, before, or prior “to that” the recipient has received or receives the transplant. Correction is required, for example, to recite after or before “the recipient has received the transplant”, or “prior to the recipient receiving a transplant”.
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. Claim 16 is indefinite in that the method encompasses administering to the recipient an anti-CCR7 antibody “or antigen binding fragment thereof”, but in parts (a)-(d), which specifies limitations regarding administration regimens, only an “anti-CCR7 antibody” is mentioned. It is therefore unclear whether the claim would encompass administering antibody fragments, as recited in line 3, or whether the claims require administration of an antibody, as recited (a)-(d). A similar issue exists for the functional requirement in lines 4-5, wherein “the anti-CCR7 antibody effects at least one of killing an induction of apoptosis of CCR7 expressing cells in the recipient”. Do these limitations only apply if an antibody is administered, but not in the case that an antigen-binding fragment thereof is administered? Would the claims encompass administering an antibody comprising an antigen-binding fragment of an antibody with the killing function even if the administered antibody does not have the function?
It is also unclear whether the claim would require administering an identical antibody in each step, or whether the claims would encompass antibodies with the same antigen binding fragment, but with different constant regions, or the same antibody portion with or without an attached cytotoxin, for example. This is because the claim recites different functions for the antibody or binding fragment thereof in different claim limitations. 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 or antigen binding fragment” “inhibits CCR7-dependent signaling, CCR7 dependent functions, and/or CCR7 receptor internalization”. For example, would the claim encompass using an anti-CCR7 antibody linked to a toxin to meet the first wherein clause of effecting killing, and the same antibody without the toxin could be administered in a separate step to meet the second wherein clause? Would the claim encompass administering an IgG1 anti-CCR7 antibody to meet the first wherein clause and performing a second administration of a neutralizing IgG4 version of the same antibody to meet the second clause (in this scenario, the IgG4 antibody would comprise an antigen binding fragment of the IgG1 antibody that effects killing, and would also function to inhibit CCR7 dependent signaling).
Additionally, Claim 16 recites administering an anti-CCR7 antibody, and requires at least one specific administration protocol as set forth in a)-d). The then claim further recites that the treatment comprises “at least one administration to the recipient of the anti-CCR7 antibody separate from the transplant”. It is unclear if the claims require multiple administrations of the antibody. For example, could one select an administration regimen according to part a), wherein the antibody is administered after the transplant, and that would also meet the limitations of wherein the treatment comprises “at least one administration separate from the transplant”. Or does the wherein clause intend to specify a further required administration step in addition to that recited in parts a)-d). Furthermore, the claim is directed to a method of preventing or treating GVHD. However, the last wherein clause specifies that “wherein the treatment” comprises at least one administration separate from the transplant. Is this step required for a prevention method, or would a method of preventing GVHD only require one of the limitations from a)-d), and the limitations of the last wherein clause are only required when “treating” GVHD?
Claim 19 recites the limitation "the N-terminal extracellular domain" in line 2 and “the Kd of a reference anti-CCR7 antibody” in line 3, “the heavy chain” and “the light chain” in lines 5-6. There is insufficient antecedent basis for these limitations in the claim.
Claim 20 recites the limitation "the anti-CCR7 antibody thereof" in lines 1-2. The claim is unclear and indefinite since it is not clear what the antibody “thereof” encompasses.
Claim 21 is indefinite in the recitation that the anti-CCR7 antibody is an antibody having “the HVRs” of “the anti-human CCR7 antibody” of which the amino acid sequence of “the heavy chain” is SEQ ID NO :1 and “the light chain” is SEQ ID NO: 2. The claims lack antecedent basis for these terms.
Claim 26 recites the limitation "the graft versus tumor effect" and “the graft versus leukemia effect” in lines 2-3. There is insufficient antecedent basis for these limitations in the claim.
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 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 9/8/25 have been fully considered, but they are not persuasive.
Applicant argues that WO 2013184200 teaches a narrow patient population suffering from GVHD after bone marrow transplantation in a patient with a hematological malignancy, while in contrast the present claims are broader and encompass treating GVHD in all recipients of transplants.
It is well established that a species anticipates a genus. WO 2013184200 teaches a species of method falling within the scope of the instant claims, and thus anticipates (or renders obvious, see below) the claimed method.
Applicant further argues that the claimed invention provides unexpected advantages citing Fig. 5B of the specification, in that it maintains graft versus leukemia effects.
As an initial matter, allegations of unexpected results are not effective to rebut a rejection under 102. Regarding the 103 rejections below, maintaining graft versus leukemia effects would be expected. For example, WO 2013184200 teaches that the method allows for regeneration of adaptive immunity, and breaks immune tolerance to cancer, thereby treating cancer and maintains grafter vs. leukemia (See page 26, in particular). See also Coghill, which teaches that inhibition of CCR7 in the early post-transplantation period represents a feasible new therapeutic approach for GVHD attenuation without compromising GVL (i.e. graft versus leukemia) responses.
Applicant further argues that as evidence by Fowler, the state of the art was such that using depleting CCR7 antibodies was not preferred, since they teach the desirability of identifying neutralizing IgG4 antibodies.
The claims recite no limitations regarding IgG4 antibody isotype, nor do they require depleting antibodies as argued by Applicant. Rather, the claims recite a limitation that the antibody “effects at least one of killing and induction of apoptosis of CCR7 expressing cells”. For example, a neutralizing antibody that deprives CCR7 expressing cells of necessary survival signals, thus causing cell death, would be within the scope of the instant claims. Furthermore, “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….”. In re Fulton, 391 F.3d 1195, 73 USPQ2d 1141 (Fed. Cir. 2004).
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.
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).
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.
No claim is allowed.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644