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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05 December 2025, has been entered.
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 05 December 2025, have been entered in full. Claim 15 is withdrawn from consideration as being drawn to a non-elected invention. Claims 4, 5, 7-9 are canceled. Claims 1, 2, 6 and 10 are amended. Claims 1-3, 6, 10-14 and 16 are under examination.
MATTER OF RECORD
Applicant is reminded of their election with traverse of Group I (drawn to a method of treating cancer in subjects in need thereof comprising administering an anti-EPO antibody) and the cancer species election of glioblastoma.
Withdrawn Objections And/Or Rejections
The rejection to claims 2 and 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-
AIA ), second paragraph, as set forth at pages 3-4 of the previous Office Action (26 August 2025), is withdrawn in view of the amendment (05 December 2025).
The rejection to claims 1, 4 and 6 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-
AIA ), first paragraph, written description, as set forth at pages 5-6 of the previous Office Action (26 August 2025), is withdrawn in view of the amendment (05 December 2025).
The rejection to claims 1-4, 6, 11-14 on the ground of nonstatutory double
patenting as being unpatentable over claims 1-3, 5 and 6 of U.S. Patent No. 11,078,270 in view of Abderrahim et al. (US 2008/0260746; published 23 October 2008), as set forth at pages 6-9 of the previous Office Action (26 August 2025), is withdrawn in view of the submitted Terminal Disclaimer. The terminal disclaimer filed on 05 December 2025 has been reviewed and is accepted. The terminal disclaimer has been recorded (05 December 2025).
The objection to claim 6, as set forth at page 10 of the previous Office Action (26 August 2025), is withdrawn in view of the amendment (05 December 2025).
The rejection to claims 1-4, 6, 10-14 and 16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth at page 10 of the previous Office Action (26 August 2025), is withdrawn in view of the amendment (05 December 2025).
The rejection to claims 1-4, 6, 10-14 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-
AIA ), first paragraph, written description, new matter, as set forth at pages 11-13 of the previous Office Action (26 August 2025), is withdrawn in view of the amendment (05 December 2025).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-3, 6, 11-14 and 16 remain rejected under 35 U.S.C. 103 as being unpatentable over Abderrahim et al. (Reference of record; US 2008/0260746; published
23 October 2008) in view of Wachtel et al. (Survival benefit of temozolomide as treatment
for glioblastoma; A population based analysis. Laboratory Investigation, Vol. 92, Supp. SUPPL. 1, pp. 437A. Abstract Number: 1823, Feb 2012). The basis for this rejection is set forth at pages 13-17 of the previous Office Action (26 August 2025).
APPLICANT’S ARGUMENT ONE: Applicant argues that the presently claimed invention is directed to a method of treating cancer using a negative functional modulator of erythropoietin (EPO), specifically an anti-EPO antibody, administered in a pharmaceutical composition that also includes modulators of sphingosine-1-phosphate (S1P) metabolism and/or molecules acting on S1P receptors. Applicant argues that the antibody binds to human EPO (SEQ ID NO:2) or a fragment thereof, and the composition may further include temozolomide.
Applicant submits that the Abderrahim reference describes antibodies targeting novel EPO variants-truncated or exon-rearranged forms of EPO that differ structurally from the mature EPO sequence. Applicant argues that these variants, such as Perov, EPOvl, EPOv2, and EPOv3, are designed to retain tissue-protective activity without stimulating erythropoiesis. Applicant argues that the antibodies described by Abderrahim are specific to these variants and are not directed to SEQ ID NO:2, which encodes mature human EPO. Applicant maintains that the reference does not teach or suggest antibodies that bind the claimed epitope, nor does it disclose the use of such antibodies as negative functional modulators of EPO activity in cancer therapy.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. The instant claims do not recite an anti-EPO that comprises a specific sequence. That is to say, the instant claims do not recite that the anti-EPO antibody comprises a SEQ ID NO: to the variable heavy (VH) domain and a SEQ ID NO: to the variable light (VL) domain. The instant claims do not recite that the anti-EPO antibody comprises 6 SEQ ID Nos: to the complementarity derived regions (CDRs)(three CDRs in the VH and three CDRs in the VL).
Instead, the instant claims are drawn to any anti-EPO antibody that binds human EPO or a fragment thereof (see instant claim 1) or any monoclonal anti-EPO antibody that binds sequences selected from the group consisting of AA 1-162, AA 1-26 and AA 1-166 of SEQ ID NO:3 (see instant claim 6).
2. Abderrahim et al. teach the invention relates to novel EPO polypeptides and their uses, particularly for therapeutic or prophylactic treatment in human subjects. Further included are antibodies specific for the novel EPO polypeptides of the present invention (abstract and paras 0009, 0022, 0258-0264). Abderrahim et al. teach antibodies of the invention include monoclonal or polyclonal antibodies (paras 0268 and 0324-0325). Abderrahim et al. teach the antibodies can be used to treat glioblastoma (para 0313).
Abderrahim et al. teach the novel EPO polypeptides are variant polypeptides consisting of a polypeptide differing from the sequence set forth at SEQ ID NO:3 (human immature EPO) by the lack of at least one of the amino acids 56 (Cysteine)-193 (Arginine) of SEQ ID NO: 3, or a variant or an analog of said polypeptide (paras 0013- 0017 and 0051).
The Examiner maintains that an antibody made against human EPO polypeptide (SEQ ID NO:3), wherein said human EPO polypeptide lacks one amino acid residue, such as amino acid residue 193 in SEQ ID NO:3 as taught by Abderrahim, would still be able to bind SEQ ID NO:2 or a fragment thereof (instant claim 1) or sequences selected from the group consisting of AA 1-162, AA 1-26 and AA 1-166 of SEQ ID NO:3 (instant claim 6).
APPLICANT’S ARGUMENT TWO: Applicant argues that Abderrahim is entirely silent on the S1P pathway and that the reference does not mention modulators of S1P metabolism or molecules acting on S1P receptors, such as SW-2871, VPC24191, AUY954, SEW2871, VPC23153, DS-GS-44, or VPC01091. Applicant maintains that the inclusion of these agents in the claimed composition introduces a distinct and novel therapeutic mechanism that is not disclosed or suggested by Abderrahim.
Applicant’s arguments have been fully considered but are not found persuasive for the following reason: 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). Claim 1 also recites “temozolomide”. Wachtel et al. teach temozolomide.
APPLICANT’S ARGUMENT THREE: Applicant argues that Wachtel cannot correct Abderrahim's deficiencies nor can it provide for the missing link. Applicant argues that Wachtel describes the clinical benefit of temozolomide in glioblastoma multiforme when combined with radiotherapy. Applicant argues that while Wachtel supports the use of temozolomide in this context, it does not mention EPO, anti-EPO antibodies, or S1P-related compounds. Applicant argues that there is no teaching or suggestion in Wachtel that temozolomide should and could be combined with EPO inhibition or S1P modulation.
Applicant argues that the Examiner's rationale for combining Abderrahim and Wachtel fails to account for the inventive integration of three distinct therapeutic modalities: EPO inhibition, S1P pathway modulation, and alkylating chemotherapy. Applicant argues that this tri-modal approach is not disclosed or suggested in either reference and reflects a novel therapeutic strategy based on mechanistic insights into tumor biology. Applicant maintains that the claimed invention is not a routine combination of known agents but a non-obvious and inventive method of treating cancer. The claimed combination yields unexpected synergistic effects, including enhanced tumor suppression through dual modulation of angiogenesis and immune signaling, improved delivery and efficacy of anti-EPO antibodies in the presence of S1P modulators, and potential reduction in temozolomide resistance via EPO pathway inhibition. Applicant argues that these effects are not predictable from the teachings of Abderrahim or Wachtel and further support the non-obviousness of the claimed invention.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. Applicant argues that the Examiner's rationale for combining Abderrahim and Wachtel fails to account for the inventive integration of three distinct therapeutic modalities: EPO inhibition, S1P pathway modulation, and alkylating chemotherapy. Applicant argues that this tri-modal approach is not disclosed or suggested in either reference and reflects a novel therapeutic strategy based on mechanistic insights into tumor biology.
The Examiner maintains that this argument is not found persuasive because in addition to an anti-EPO antibody that recognizes/binds human EPO (SEQ ID NO:2) or a fragment thereof and pharmaceutically acceptable excipients, claim 1 requires
a therapeutically effective amount of one or more modulators of S1P metabolism AND/OR natural or synthetic molecules that act on the receptors S1P, wherein said natural or synthetic molecules that act on the receptor of S1P are selected from the group consisting of antiS1P, anti-S1PRs, SW-2871, VPC24191, AUY954, SEQ2871, (5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[trifluoromethyl)phenyl]-1,2,4-oxadiazole),VPC23153, DS-GS-44 and VPC011091; OR Temozolomide.
The claim reads on administering anti-EPO antibody and Temozolomide. Thus, it is unclear what is meant by “three distinct therapeutic modalities: EPO inhibition, S1P pathway modulation, and alkylating chemotherapy”.
2. The arguments of unexpected results are not found persuasive because Abderrahim and Wachtel teach the use of anti-EPO antibodies and temozolomide, respectively, to treat glioblastoma.
3. Wachtel et al. teach improved survival after diagnosis of glioblastoma when temozolomide is administered with radiotherapy versus treatment by radiotherapy alone, which means adding temozolomide to the treatment increased glioblastoma patient survival. The reference does not teach against adding temozolomide to anti-EPO treatments.
Wachtel et al. clearly teach the benefits of temozolomide in the treatment of glioblastoma. Abderrahim teaches the use of their anti-EPO antibodies in treatment for glioblastoma. Based on the combined references, it would be obvious to add temozolomide to anti-EPO antibody treatment of glioblastoma.
One skilled in the art would also have expected success combining an anti-EPO antibody with temozolomide because “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) and MPEP § 2144.06
The scientific reasoning and evidence as whole indicates that the rejection should be maintained.
Claims 1-3, 6, 10 and 16 remain rejected under 35 U.S.C. 103 as being unpatentable over Nico et al. (Reference of record; J Neurooncol Vol. 102:51-58, 2011) in view of Wachtel et al. (Laboratory Investigation, Vol. 92, Supp. SUPPL. 1, pp. 437A. Abstract Number: 1823; February 2012). The basis for this rejection is set forth at pages 17-20 of the previous Office Action (26 August 2025).
APPLICANT’S ARGUMENT ONE: Applicant argues that Nico does not describe Applicants' invention. Applicant argues that Nico teaches the role of erythropoietin (EPO) and its receptor (EPOR) in glioma-induced angiogenesis. Applicant argues Nico using immunohistochemistry and the chick embryo chorioallantoic membrane (CAM) assay, demonstrates that glioma tissues express EPO and EPOR, and that this expression correlates with increased microvascular density. Co-administration of anti-EPO antibodies in the CAM assay significantly inhibited angiogenesis, suggesting that glioma cells secrete EPO which acts in a paracrine fashion to stimulate endothelial cells and promote vascularization. Applicant maintains that Nico's findings are limited to the characterization of EPO's pro-angiogenic role and the observation that blocking EPO can reduce angiogenesis in an in vivo model. Applicant submits that Nico does not teach or suggest the use of anti-EPO antibodies as a therapeutic agent for direct cancer treatment, nor does it disclose or imply combination with any chemotherapeutic agents, including temozolomide. Applicant submits that the study described by Nico focused on mechanistic insights into glioma angiogenesis, not on therapeutic regimens or clinical outcomes.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
The instant claims are drawn to a method of treating cancer (elected species being treating glioblastoma).
Nico teaches that angiogenesis is crucial to the growth of malignant gliomas. Nico teaches that EPO is secreted by glioma tumor cells, which promotes angiogenesis. Nico teaches administering anti-EPO or anti-EPOR blocks glioma angiogenesis.
Contrary to the presented arguments, there is a correlation between angiogenesis and the growth of malignant tumors. Tumors need a blood supply (i.e. angiogenesis) to grow and metastasize to other parts of the body. Inhibiting glioma-induced angiogenesis is a way of treating glioblastoma because the blood supply (i.e. angiogenesis) is being cut off from the tumor.
APPLICANT’S ARGUMENT TWO: Applicant argues that Wachtel cannot correct Nico's deficiencies nor can it provide for the missing link. Applicant argues that Wachtel describes epidemiological data showing improved survival in glioblastoma patients treated with temozolomide and radiotherapy. Applicant argues that while Wachtel supports the clinical utility of temozolomide, it is entirely silent on EPO, EPOR, angiogenesis, or the use of anti-EPO antibodies. Applicant argues that Wachtel fails to teach or suggest that temozolomide should and could be combined with anti-EPO therapy, nor is there any indication of a mechanistic or synergistic relationship between these modalities.
Applicant submits that the Examiner's assertion that one of ordinary skill in the art would have been motivated to combine Nico's anti-EPO strategy with Wachtel's temozolomide regimen lacks factual support. Applicant argues that the combination of the cited references address distinct biological mechanisms-angiogenesis versus DNA alkylation-and does not provide any rationale for an integration.
Applicant maintains that the claimed invention goes beyond a simple combination of known agents. It involves a targeted anti-EPO antibody that binds a specific epitope (SEQ ID NO:2), formulated in a pharmaceutical composition that may also include modulators of S1P metabolism or S1P receptor ligands, and optionally temozolomide. Applicant maintain this multi-modal approach reflects a novel therapeutic strategy that is not suggested by Nico or Wachtel, alone or in combination.
Applicant argues that the claimed invention is based on the insight that EPO signaling contributes to glioma progression via angiogenesis, and that its inhibition-combined with modulation of the S1P pathway and/or chemotherapy-can yield enhanced anti-tumor effects.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. Wachtel et al. clearly teach that benefits of temozolomide in the treatment of glioblastoma. The reference does not teach against adding temozolomide to anti-EPO treatments.
2. Applicant argues that the combination of the cited references address distinct biological mechanisms-angiogenesis versus DNA alkylation-and does not provide any rationale for an integration.
This argument is not found persuasive because many cancer treatments provide an integration that involve numerous pathways/mechanisms such as anti-angiogenesis, damaging the DNA of cancer cells, etc.
3. Applicant argues that the claimed invention involves a targeted anti-EPO antibody that binds a specific epitope (SEQ ID NO:2), formulated in a pharmaceutical composition that may also include modulators of S1P metabolism or S1P receptor ligands, and optionally temozolomide. Applicant maintain this multi-modal approach reflects a novel therapeutic strategy that is not suggested by Nico or Wachtel, alone or in combination.
This argument is not found persuasive. It is unclear how the claimed invention goes beyond a simple combination of known agents when the method uses a pharmaceutical composition that may include modulators of S1P metabolism or S1P receptor ligands, and optionally temozolomide, in addition to the anti-EPO antibody. On the contrary, the claimed invention encompasses agents that are known to be used for treating glioblastoma.
4. Applicant argues that the claimed invention is based on the insight that EPO signaling contributes to glioma progression via angiogenesis, and that its inhibition-combined with modulation of the S1P pathway and/or chemotherapy-can yield enhanced anti-tumor effects.
This argument is not found persuasive. As was stated above, Nico teaches that EPO is secreted by glioma tumor cells, which promotes angiogenesis. Nico teaches that angiogenesis is crucial to the growth of malignant gliomas. A tumor needs a blood supply (i.e. angiogenesis) to grow and metastasize to other parts of the body. Wachtel et al. teach improved survival after diagnosis of glioblastoma when temozolomide was administered with radiotherapy versus treatment by radiotherapy alone. Temozolomide is a chemotherapy drug.
The scientific reasoning and evidence as whole indicates that the rejection should be maintained.
NEW CLAIM REJECTIONS/OBJECTIONS
Claim Rejections-35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph
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.
Claim 16 is 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 16 recites the limitation "..wherein said alkylating agent..". Claim 16 depends from claim 1. There is insufficient antecedent basis for the limitation “alkylating agent”.
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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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/R.M.D/Examiner, Art Unit 1647 1/5/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647