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 .
Detailed Action
The Amendments and Remarks filed 12/19/25 in response to the Office Action of 9/17/25 are acknowledged and have been entered.
Claims 1, 4-6, 8, 9, and 12-18 are pending.
Claims 1, 8, 9, 18, and 19 have been amended by Applicant.
Claims 1, 4-6, 8, 9, and 12-18 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
The rejection of claims under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Prestwich et al (WO 2011/094149 A1; 8/4/11) is withdrawn.
The rejection of claims under 35 U.S.C. 103(a) as being unpatentable over Ferber et al (eLIFE, 2017, 6(e25281): 1-34; 3/19/23 IDS) is withdrawn.
The rejection of claims under 35 U.S.C. 103 as being unpatentable over Ferber et al (eLIFE, 2017, 6(e25281): 1-34; 3/19/23 IDS) in view of Bestebroer et al (Blood, 2007, 109(7): 2396-2943) is withdrawn.
The rejection of claims 13 and 15-17 under 35 U.S.C. 103 as being unpatentable over Ferber et al (eLIFE, 2017, 6(e25281): 1-34; 3/19/23 IDS) in view of Kreeger et al (US 2019/0241665 A1; 8/8/19; 3/19/23 IDS) is withdrawn.
The rejection of claims under 35 U.S.C. 103 as being unpatentable over Ferber et al (eLIFE, 2017, 6(e25281): 1-34; 3/19/23 IDS) in view of Jin et al (Bioconjugate Chemistry, 2011, 22: 2568-2572) is withdrawn.
The rejection of claims under 35 U.S.C. 103 as being unpatentable over Ferber et al (eLIFE, 2017, 6(e25281): 1-34; 3/19/23 IDS) in view of Omuro et al (Neuro-Oncology, 2018, 20(5): 674-686) is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claim(s) 1, 8, 9, and 14 remain rejected under 35 U.S.C. 103 as being unpatentable over Ferber et al (eLIFE, 2017, 6(e25281): 1-34; 3/19/23 IDS) in view of Kreeger et al (US 2019/0241665 A1; 8/8/19; 3/19/23 IDS).
Ferber et al teaches P-selectin is highly expressed in glioblastoma and P-selectin expression in glioblastoma correlates with patient survival (page 10 and Figure 3, in particular). Ferber et al further suggests targeting P-selectin in glioblastoma may have additional therapeutic benefit because high expression of P-selectin correlate with poor patient survival (page 21, in particular). Ferber et al further teaches a conjugate comprising paclitaxel (PTX) conjugated to a dendritic polyglycerol sulfate (dPGS) for treating glioblastoma (Abstract, in particular). Ferber et al further teaches dPGS is able to cross the blood-brain barrier (BBB), binds to P-selectin, inhibits P-selectin, and accumulate in intracranial tumors (Abstract and lines 2-3 on page 3, in particular). Ferber et al further teaches the anti-proliferative activity of PTX on glioblastoma cells is retained in the conjugate comprising PTX and dPGS (Figure 4, in particular) and that the conjugate is targeted to intracranial tumors (Figure 5, in particular).
Ferber et al does not specifically teach administering an inhibitor of P-selectin that is an antibody that binds to and inhibits P-selectin that is attached to or not attached to a therapeutic agent such as PTX, administering an inhibitor of P-selectin that is a small molecule agent, or administering an inhibitor of P-selectin that is a polynucleotide. However, these deficiencies are made up in the teachings of Kreeger et al.
Kreeger et al teaches inhibitors of P-selectin for therapeutic treatment include (unconjugated) antibodies that bind and inhibit P-selectin (crizanlizumab and inclacumab) and small molecule agents (rivipansel and tinzaparin) ([0039]-[0040], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a rendered obvious by Ferber et al comprising treating just any subject diagnosed with glioblastoma, such as a subject with an early stage glioblastoma or a subject with glioblastoma before or after resection, by administering a therapeutically effective amount of the conjugate comprising PTX and dPGS of Ferber et al to the subject because Ferber et al teaches the conjugate is to be used to treat glioblastoma, the anti-proliferative activity of PTX on glioblastoma cells is retained in the conjugate, and that the conjugate is targeted to intracranial tumors.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a first combined method comprising the method rendered obvious by Ferber et al wherein dPGS of the conjugate is substituted with an antibody that binds and inhibits P-selectin (such as crizanlizumab or inclacumab) as the targeting agent of the conjugate and a therapeutically effective amount of the conjugate is intracranially administered to the subject with glioblastoma because both dPGS of the conjugate and the antibodies of Kreeger et al function by targeting and inhibiting P-selectin. This is an example of a simple substitution of one known element (P-selectin targeting and inhibiting antibodies of Kreeger et al) in place of (P-selectin targeting and inhibiting reagent of dPGS of Ferber et al) of the administered conjugate of Ferber et al to obtain predictable results.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a second combined method comprising the method rendered obvious by Ferber et al wherein a therapeutically effective amount of antibodies that bind and inhibit P-selectin (such as crizanlizumab or inclacumab) are further intracranially administered (un-conjugated) to the subject with glioblastoma because like dPGS of the conjugate inhibiting P-selectin, antibodies that bind and inhibit P-selectin (such as crizanlizumab or inclacumab) also inhibit P-selectin, which Ferber et al identifies as being upregulated in glioblastoma and that levels of P-selectin in glioblastoma correlates with patient survival and because Ferber et al suggests targeting P-selectin in glioblastoma may have additional therapeutic benefit because high expression of P-selectin correlates with poor patient survival (page 21, in particular).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 12/19/25, Applicant argues Ferber does not disclose or suggest that P-selectin inhibition would be therapeutically effective in glioblastoma. Applicant further indicates one would not be motivated to administer the anti-P-selectin antibodies of Kreeger et al to subjects with glioblastoma because Kreeger et al teaches the anti-P-selectin antibodies provide therapeutic benefit by inhibiting metastasis and glioblastomas rarely metastasize. Applicant further argues cited references do not teach or suggest, with a reasonable expectation of success, substituting the delivery-focused, ligand-mimicking dPGS of Ferber with an antibody inhibitor of P-selectin.
The amendments to the claims and the arguments found in the Reply of 12/19/25 have been carefully considered, but are not deemed persuasive. In regards to the argument that Ferber does not disclose or suggest that P-selectin inhibition would be therapeutically effective in glioblastoma, Ferber et al suggests targeting P-selectin in glioblastoma may have additional therapeutic benefit because high expression of P-selectin correlate with poor patient survival (page 21, in particular). Further, when substituting P-selectin targeting and inhibiting antibodies of Kreeger et al in place of P-selectin targeting and inhibiting reagent of dPGS of Ferber et al as the targeting agent of the conjugate to target P-selectin with a conjugate comprising paclitaxel (PTX) in the “first combined method” discussed above, the PTX of the targeted complex would predictably inhibit growth and proliferation of P-selectin-expressing glioblastoma cells even if P-selectin is not inhibited because paclitaxel is a known mitotic inhibitor that is highly potent against glioblastoma cells (first full paragraph on page 2 of Ferber et al, in particular).
In regards to the argument one would not be motivated to administer the anti-P-selectin antibodies of Kreeger et al to subjects with glioblastoma because Kreeger et al teaches the anti-P-selectin antibodies provide therapeutic benefit by inhibiting metastasis and glioblastomas rarely metastasize, the examiner disagrees. One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a first combined method comprising the method rendered obvious by Ferber et al wherein dPGS of the conjugate is substituted with an antibody that binds and inhibits P-selectin (such as crizanlizumab or inclacumab) as the targeting agent of the conjugate and a therapeutically effective amount of the conjugate is intracranially administered to the subject with glioblastoma because both dPGS of the conjugate and the antibodies of Kreeger et al function by targeting and inhibiting P-selectin. This is an example of a simple substitution of one known element (P-selectin targeting and inhibiting antibodies of Kreeger et al) in place of (P-selectin targeting and inhibiting reagent of dPGS of Ferber et al) of the administered conjugate of Ferber et al to obtain predictable results. This “first” combined method uses the anti-P-selectin antibodies to target P-selectin (just as dPGS targets P-selectin) and is not designed to specifically inhibit P-selectin. Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a second combined method comprising the method rendered obvious by Ferber et al wherein a therapeutically effective amount of antibodies that bind and inhibit P-selectin (such as crizanlizumab or inclacumab) are further intracranially administered (un-conjugated) to the subject with glioblastoma because like dPGS of the conjugate inhibiting P-selectin, antibodies that bind and inhibit P-selectin (such as crizanlizumab or inclacumab) also inhibit P-selectin, which Ferber et al identifies as being upregulated in glioblastoma and that levels of P-selectin in glioblastoma correlates with patient survival and because Ferber et al suggests targeting P-selectin in glioblastoma may have additional therapeutic benefit because high expression of P-selectin correlates with poor patient survival (page 21, in particular).
In regards to the argument cited references do not teach or suggest, with a reasonable expectation of success, substituting the delivery-focused, ligand-mimicking dPGS of Ferber with an antibody inhibitor of P-selectin, the examiner maintains one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a first combined method comprising the method rendered obvious by Ferber et al wherein dPGS of the conjugate is substituted with an antibody that binds and inhibits P-selectin (such as crizanlizumab or inclacumab) as the targeting agent of the conjugate and a therapeutically effective amount of the conjugate is intracranially administered to the subject with glioblastoma because both dPGS of the conjugate and the antibodies of Kreeger et al function by targeting and inhibiting P-selectin. This is an example of a simple substitution of one known element (P-selectin targeting and inhibiting antibodies of Kreeger et al) in place of (P-selectin targeting and inhibiting reagent of dPGS of Ferber et al) of the administered conjugate of Ferber et al to obtain predictable results.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
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 12, 13, and 15-17 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.
Claims 12, 13, and 15-17 are rejected because claims 12, 13, 15, and 17 all recite “…wherein said agent is….” There is insufficient antecedent basis for “said agent” in the claims.
Claim Rejections - 35 USC § 103
Claim(s) 1, 4-6, 8, 9, 14, 18, and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ferber et al (eLIFE, 2017, 6(e25281): 1-34; 3/19/23 IDS) in view of Kreeger et al (US 2019/0241665 A1; 8/8/19; 3/19/23 IDS) as applied to claims 1, 8, 9, and 14 above, and further in view of Omuro et al (Neuro-Oncology, 2018, 20(5): 674-686).
Teachings of Ferber et al and Kreeger et al are discussed above.
Ferber et al and Kreeger et al do not specifically teach administering an immunomodulating checkpoint inhibitor. However, these deficiencies are made up in the teachings of Omuro et al.
Omuro et al teaches method of treating glioblastoma administering the checkpoint inhibitor nivolumab optionally in combination with the checkpoint inhibitor ipilimumab (Abstract, in particular).
One ordinary skill in the art would have been motivated, with a reasonable expectation of success, to treat just any patient with glioblastoma by performing the combined methods of Ferber et al and Kreeger et al wherein checkpoint inhibitor(s) of Omuro et al, optionally as a single composition, are administered to the subjects with glioblastoma because both the combined method of Ferber et al and Kreeger et al and the checkpoint inhibitors of Omuro provide therapeutic benefit to subjects with glioblastoma. This is an example of both (1) combining prior art elements according to known methods to yield predictable results and (2) some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
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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/SEAN E AEDER/Primary Examiner, Art Unit 1642