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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/8/2025 has been entered.
Claims 1-15, 17, and 26 have been cancelled.
Applicant's arguments filed 10/8/2025 have been fully considered but they are not persuasive.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 16, 18-25, and 27-31 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 16, 18-25, and 27-31 are not original claims. They were added by amendment on 4/7/2022.
Claim 16 has now been amended to recite:
A method of treating a hyperproliferative hematological disorder in a subject, the method comprising administering an anti-CCR7 antibody to the subject, wherein the subject has hyperproliferative hematological disorder that is refractory to and/or has relapsed after treatment with a Bruton's tyrosine kinase (BTK) inhibitor and wherein the anti-CCR7 antibody is administered after the subject has developed resistance to or relapsed following the BTK inhibitor treatment, and wherein the antibody is administered simultaneously, separately or sequentially with at least one of a BTK inhibitor and a Bcl-2 inhibitor.
No basis has been pointed to for the amendments and none is apparent. The specification does not disclose administering a BTK inhibitor to a subject with a hyperproliferative hematological disorder after the subject has become refractory to and/or has relapsed after treatment with a BTK inhibitor.
Claim 16 and its dependent claims constitute new matter.
Claim 29 has been amended to recite:
The method of claim 16, wherein the hyperproliferative hematological disorder is refractory to and/or has relapsed after treatment with at least one of a further BTK inhibitor and a chemotherapeutic agent other than a BTK inhibitor, a Bcl-2 inhibitor and an anti-CCR7 antibody.
No basis has been pointed to for the amendments and none is apparent. The specification does not disclose administering a further BTK inhibitor to a subject with a hyperproliferative hematological disorder after the subject has become refractory to and/or has relapsed after treatment with a BTK inhibitor. It appears that this claim requires that the hyperproliferative hematological disorder is refractory to and/or has relapsed after treatment with two BTK inhibitors (the first in claim 16 and the second in claim 29). No basis is seen for this claim.
Claim 29 constitutes new matter.
Applicant would have basis for the following method based on claim 16:
16. A method of treating a hyperproliferative hematological disorder in a subject, the method comprising administering an anti-CCR7 antibody to the subject, wherein the subject has hyperproliferative hematological disorder that is refractory to and/or has relapsed after treatment with a Bruton's tyrosine kinase (BTK) inhibitor and wherein the anti-CCR7 antibody is administered after the subject has developed resistance to or relapsed following the BTK inhibitor treatment, and wherein the antibody is administered simultaneously, separately or sequentially with a Bcl-2 inhibitor.
For proper dependency, claim 25 and 28-29 could be amended to recite:
25. The method of claim 16, wherein the Bcl-2 inhibitor is venetoclax or navitoclax.
28. The method of claim 27, wherein the hyperproliferative hematological disorder is additionally refractory to and/or has relapsed after treatment with a chemotherapeutic agent that is not a Bcl-2 inhibitor and/or an anti-CCR7 antibody.
29. The method of claim 16, wherein the hyperproliferative hematological disorder is additionally refractory to and/or has relapsed after treatment with a chemotherapeutic agent that is not a Bcl-2 inhibitor and/or an anti-CCR7 antibody.
Applicant is advised that the claim language proposed above is not an indication of an allowable claim. See art rejections below.
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 25 and 28-31 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.
Claim 25 lists particular BTK inhibitors. It is unclear if these are BTK inhibitors to which the subject is refractory or has relapsed after treatment with them or whether these are the BTK inhibitors to be administered as recited in the last lines of claim 16 after the subject has become refractory to and/or has relapsed after treatment with a BTK inhibitor. The claim is confusing.
Claim 28 is confusing in reciting “wherein the hyperproliferative hematological disorder is refractory to and/or has relapsed after treatment with a chemotherapeutic agent other than a BTK inhibitor…” as claim 16 requires that the subject has become refractory to and/or has relapsed after treatment with a BTK inhibitor. If the claim intended that the subject has become refractory to and/or has relapsed after other treatments in addition to BTK inhibitors, the claim language of claim 28 as it depends upon claims 16 and 27 does not make this clear. Claim 29 is also unclear for the same reason.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 16, 18-19, 23, 25, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bender et al. (WO 2018/142322, of record).
Bender et al. discloses administering an anti-CCR7 antibody to a subject to treat hyperproliferative hematological disorders such as chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma, and Burkitt’s lymphoma. The antibody can be chimeric, humanized or human. The cancer can be a resistant or relapsed cancer, including a cancer resistant to tyrosine kinase inhibitors. See at least paragraphs [0281-0289]. These would include those resistant to known Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib. See at least paragraphs [0297-0298]. The antibody can be administered with other drugs including a Bcl-2 inhibitor such as venetoclax or navitoclax. The anti-CCR7 antibody can also be administered with chemotherapeutic agents such as fludarabine and cyclophosphamide. Administering idelalisib is disclosed. Co-administration can be concurrent or sequential. See at least abstract, paragraphs [0012-0014, 0025, 0030, 0056, 0292-0298, 0306-0307, 0309]. Bender et al. fairly includes the treatment of treatment naïve patients for an anti-CCR7 antibody or Bcl-2 inhibitor as no requirement for any pre-treatment is disclosed. (See instant claim 27.) The anti-CCR7 antibodies can be administered with Bcl-2 inhibitors such as venetoclax. The anti-CCR7 antibody can be conjugated to the Bcl-2 inhibitor. See paragraphs [0307 and 0309 ] and claim 22. See also claims 29-30 and 39-40.
With respect to claim 16, the disclosure of sequential administration in paragraphs [0292-0298] fairly includes treating with the BTK inhibitor first and followed later by treating with the anti-CCR7 antibody and Bcl-2 inhibitor such as venetoclax or navitoclax. Bender et al. fairly discloses administering an anti-CCR7 antibody and a Bcl-2 inhibitor after the cancer (such as CLL) has become resistant (i.e. refractory) to treatment with BTK inhibitors.
Note that the claims do not require any particular anti-CCR7 antibody. Note that the claims do not require any particular therapeutic effects from any of the agents administered. Note that the claims do not require administering any particular amount of any of the agents.
Applicant’s arguments are unpersuasive. Bender et al. discloses the specific clinical scenario recited in the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 16, 18-25, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Bender et al. (WO 2018/142322, of record) in view of Woyach et al. (2017) and Back et al. (WO 2017/025569, of record).
Bender et al. is applied as above. It does not disclose the CCR7 antibody limitations of claims 20-24.
Woyach et al. disclosed treating ibrutinib-refractory chronic lymphocytic leukemia (CLL) with other therapeutics, including Bcl-2 inhbitors such as venetoclax. See at least abstract, Table 1, and pages 1272-73 starting at section on clinical data for treatment of patients after ibrutinib relapse.
Back et al. discloses an anti-CCR7 antibody having a VH of SEQ ID NO: 1 and a VL of SEQ ID NO: 2. See instant claim 24. SEQ ID NOS: 1 and 2 of Back et al. correspond to instant SEQ ID NOS: 1 and 2, respectively. Back et al. discloses a particularly preferred humanized anti-CCR7 antibody having a VH of SEQ ID NO: 61 and a VL of SEQ ID NO: 64. SEQ ID NOS: 61 and 64 correspond to instant SEQ ID NOS: 4 and 5, respectively. An antibody having a heavy chain constant domain of SEQ ID NO: 80 is disclosed. SEQ ID NO: 80 corresponds to instant SEQ ID NO: 10. See at least page 29, lines 13-19. Anti-CCR7 antibodies meeting the limitations of instant claims 20 and 22 are disclosed. See at least page 3, lines 8-15, and page 6, lines 7-15. Anti-CCR7 antibodies meeting the limitations of instant claim 21 are disclosed. See at least page 23, lines 22-25. Treatment of hyperproliferative hematological disorders such as chronic lymphocytic leukemia (CLL) and Burkitt’s lymphoma is disclosed. See also at least abstract; claims; and page 4, lines 8-16; page 5, lines 3-7; page 22, lines 8-21; and page 26, lines 1-4.
It is again noted that page 22 of the instant specification discloses that the CAP-100 antibody was known in the prior art. It is the antibody of Back et al. having a VH of SEQ ID NO: 61, a heavy chain constant domain of SEQ ID NO: 80, and a VL of SEQ ID NO: 64 where these sequences correspond to instant SEQ ID NOS: 4, 10, and 5, respectively. US 2018237529 as disclosed in the instant specification corresponds to U.S. Patent Application Publication 2108/0237529. This is the PGPUB for U.S. application 15/751,169 which was the 371 filing of PCT/EP2016/06905. PCT/EP2016/069095 published as WO 2017/025569.
It would have been obvious to use any of the anti-CCR7 antibodies of Back et al. in the methods of Bender et al. in order to treat hyperproliferative hematological disorders such as chronic lymphocytic leukemia (CLL) and Burkitt’s lymphoma after the subject has developed resistance to or relapsed following BTK inhibitor treatment. Back et al. discloses humanized antibodies as recited in instant claim 23. Bender et al. fairly discloses administering an anti-CCR7 antibody and a Bcl-2 inhibitor after the cancer (such as CLL) has become resistant (i.e. refractory) to treatment with BTK inhibitors. Administration of Bcl-2 inhibitors such as venetoclax after the cancer (such as CLL) has become resistant (i.e. refractory) to treatment with BTK inhibitors is taught and suggested by Woyach.
Applicant’s arguments are not persuasive as the prior art fairly suggests the specific clinical scenario recited in the claims.
Claims 16, 18-25, and 27-31 are rejected under 35 U.S.C. 103 as being unpatentable over Parikh (October 2018) in view of Bender et al. (WO 2018/142322, of record), Woyach, Back et al. (WO 2017/025569, of record) and Kristiansen (U.S. Patent Application Publication 2017/0304415).
Bender et al. and Woyach are applied as above.
Back et al. is applied as above. It additionally teaches that mouse antibody 729 corresponds to SEQ ID NOS: 1 and 2. A humanized form of antibody 729 is mAb650. CD20-refractory CLL tumor B-cells, from a patient unresponsive to cytostatics and anti-CD-20 monoclonal antibody therapy and considered to be anti-CD20 therapy resistant, are efficiently killed in the complement dependent cytotoxicity (CDC) assay by mAb729-2A. See at least Figures 1 and 4, Tables 5-6, Examples 2.7, 4.1, 4.2, and 4.3; and pages 44, lines 10-12 and 22-24, paragraphs [0177 and 0191]. Alemtuzumab (an anti-CD52 monoclonal antibody) and rituximab (i.e. rituxan) were used in a refractory assay. All four anti-CCR7 antibodies (11-AE, 11-17, 31-17, 31-AE, see section 5.1) mediated ADCC using isolated PBLs on an alemtuzumab-refractory CLL sample. See at least Example 4.2 and 5.2, Figure 5 and page 44 lines 26-31.
Parikh discloses the standard of care in 2018 for treatment of chronic lymphocytic leukemia (CLL). Treatment with oral targeted therapies such as ibrutinib (a BTK inhibitor), idelalisib and venetoclax (a Bcl-2 inhibitor) and treatment with anti-CD20 monoclonal antibodies such as obinutuzumab and rituximab are disclosed. See at least abstract and introduction. The reference discusses relapsed/refractory CLL progressing on ibrutinib. See pages 5-7 and Figures 2-3.
Kristiansen discloses that alemtuzumab (an anti-CD52 antibody) would have been a known anti-cancer drug for treating B-cell chronic lymphocytic leukaemia (B-CLL).
With respect to claims 16, 18-25, and 27-29, Parikh et al discloses treating a subject with relapsed/refractory CLL (i.e. relapsed after treatment with a chemotherapeutic agent other than a BTK inhibitor, a Bcl-2 inhibitor, and an anti-CCR7 antibody, see instant claims 28-29) who is naïve to ibrutinib (see instant claim 27) with the BTK inhibitor ibrutinib and if the subject then becomes refractory/relapsed to ibrutinib to then treat with a Bcl-2 inhibitor such as venetoclax. See at least Figure 3 of Parikh et al. See also Woyach. It would have been obvious to administer the Bcl-2 inhibitor with an anti-CCR7 antibody, including as a conjugate, as suggested by Bender et al. Back et al. suggests suitable anti-CCR7 antibodies that could be used that meet the limitations of claims 20-24 as set forth above. One would have been motivated to do so to provide alternate methods of therapy when other therapies were ineffective.
With respect to claims 30-31, standard chemotherapeutic agents for treating CLL include anti-CD20 antibodies such as obinutuzumab. See at least Figure 2 of Parikh et al. Administration of this antibody as the first-line treatment which is then followed by ibrutinib treatment when the subject becomes refractory/relapsed to this antibody as outlined above would meet the limitations of claims 28-31. One would have been motivated to do so to provide alternate methods of therapy when other therapies were ineffective.
With respect to claim 31, standard chemotherapeutic agents for treating CLL also include anti-CD52 antibodies such as alemtuzumab. See at least Kristiansen and Back et al. Administration of this antibody as the first-line treatment which is then followed by ibrutinib treatment when the subject becomes refractory/relapsed to this antibody as outlined above would meet the limitations of claims 28-31. In particular, Back et al. suggests that an anti-CCR7 antibody would have been expected to be successful in treating CLL tumor patients unresponsive to anti-CD20 monoclonal antibody therapy and alemtuzumab (anti-CD52 antibody) therapy. One would have been motivated to do so to provide alternate methods of therapy when other therapies were ineffective.
Applicant’s arguments are unpersuasive. Bender et al. does not require administration of ibrutinib following resistance/relapse to this drug and the references to Woyach and Parikh disclose strategies of treatment, including administering a Bcl-2 inhibitor such as venetoclax, when ibrutinib resistance/relapse has occurred. Again with respect to claims 28-31, standard chemotherapeutic agents for treating CLL include anti-CD20 antibodies such as obinutuzumab. See at least Figure 2 of Parikh et al. It would have been obvious to administer a CCL-7 antibody and Bcl-2 inhibitor (as suggested by Bender et al.) in a subject following administration of obinutuzumab as the first-line treatment which was then followed by ibrutinib treatment when the subject becomes refractory/relapsed to obinutuzumab (see claims 28-31) as suggested by the combination of the prior art. One would have been motivated to do so to provide alternate methods of therapy when other therapies were ineffective.
It would have been well understood by those of ordinary skill in the art at the time of the effective filing date to change to a different therapeutic intervention if or when a prior therapeutic intervention became ineffective. That is how medicine is practiced.
Conclusion
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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