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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/15/26 has been entered.
Claims 3, 8, and 12 are pending.
Claims 3, 8, and 12 have been amended by Applicant.
Claims 3, 8, and 12 are currently under consideration.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This Office Action contains New Rejections Necessitated by Amendments.
Rejections Withdrawn
The rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn.
Claim 12 is no longer rejected under 35 U.S.C. 103(a) or 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claims 3 and 8 remain rejected under 35 U.S.C. 103(a) as being unpatentable over Frank et al (US 2011/0165149 A1; 7/7/11) in view of Banerjee et al (Mol Cancer Res, 2016, 14(4_Supp):A25).
Frank et al teaches treating cancer by using ABCB5 binding molecules to treat ABCB5+ cancer cells (Abstract and [0044], in particular). Frank et al further teaches said method wherein the binding molecules are antibodies that bind ABCB5 ([0006], in particular). Frank et al further teaches monoclonal antibody “3C2-1D12” is an antibody that binds ABCB5 ([0009], in particular). Frank et al further teaches delivering therapeutic agents to a cell by contacting the cell with ABCB5 binding molecules conjugated to a therapeutic agent such as a chemotherapeutic or toxin to be delivered to a cancer cell ([0005], [0011], [0054], and [0168], in particular).
Frank et al does not specifically teach a method of treating GBM. However, these deficiencies are made up in the teachings of Banerjee et al.
Banerjee et al teaches administering the monoclonal anti-ABCB5 antibody “3C2-1D12” of Frank et al to subjects with ABCB5+ GBM reduces tumor growth and sensitizes the GBMs to TMZ therapy (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating ABCB5+ GBM comprising administering an effective amount of an antibody comprising an “3C2-1D12” anti-ABCB5 (to sensitize the GBM to TMZ therapy) conjugated to a chemotherapeutic and/or toxin to subjects identified as having an ABCB5+ GBM and administering Temozolomide (TMZ) to the subjects with the ABCB5+ GBM because Frank et al teaches treating ABCB5+ cancer by using ABCB5 binding molecules such as antibodies that bind ABCB5 conjugated to a chemotherapeutic and/or toxin to provide therapeutic benefit and Banerjee et al teaches monoclonal anti-ABCB5 antibody “3C2-1D12” reduces tumor ABCB5+ GBM tumor growth and sensitize ABCB5+ GBMs to TMZ therapy. This is an example of some teaching, suggestion or motivation in the prior art that would have led one of ordinary skill to modify the prior art references or combine prior art reference teachings to arrive at the claimed invention. 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 7/15/26, Applicant indicates the claims are non-obvious because it would have been unpredictable whether systemically administering ABCB5 antibody and Temozolomide would be delivered to the appropriate tissue in the brain of the animal in sufficient quantity and under sufficient conditions to alter GBM cells such that they respond to Temozolomide. Applicant further indicates the claims are non-obvious because chemosensitization of tumors is highly unpredictable and in the absence of data demonstrating that the combination of anti-ABCB5 antibody and TMZ together function better than when administered separately, the impact of anti-ABCB5 antibody and TMZ is unpredictable. Applicant further cites Ko et al (Cancer Cell Int, 2015, 15:71) and indicates the claims are non-obvious because until the combination of anti-ABCB5 antibody and TMZ is tested in vivo, the results are unpreditable because effectiveness of the agents requires that both agents are properly delivered to the correct site of action, function in vivo, and do not interfere with the activity of one another. Applicant further states the in vivo data presented in Banerjee et al shows an anti-ABCB5 antibody slowed tumor growth in immunodeficient NSG mice bearing human GBM xenografts and that Example 4 of the instant specification demonstrated an in vivo model that administration of anti-ABCB5 antibodies and Temozolomide (TMZ) resulted in significant decreases in tumor volume relative to the administration of antibody alone and that a skilled artisan would not have had a reasonable expectation of success without such data. Applicant further argues that the skilled artisan would not have predicted in view of Banerjee et al and Frank et al that an antibody conjugated to a therapeutic agent would function to enhance TMZ activity. Applicant further provided new data in the Declaration of Natasha Frank showing a human anti-ABCB5 antibody conjugated to a therapeutic agent in an orthotopic GBM model that is argued to support the teachings of the patent application that the claimed invention is useful in the treatment of GBMs.
The amendments to the claims. the arguments, and the Declaration of Natasha Frank found in the Reply of 7/15/26 have been carefully considered, but are not deemed persuasive. In regards to the indication the claims are non-obvious because it would have been unpredictable whether systemically administering ABCB5 antibody and Temozolomide would be delivered to the appropriate tissue in the brain of the animal in sufficient quantity and under sufficient conditions to alter GBM cells such that they respond to Temozolomide, Applicant is arguing limitations not required by the claims. The claims do not quire “systemic” administration (see last paragraph on page 21 of the instant specification). However, the Banerjee et al Abstract teaches “in vivo systemic administration of anti-ABCB5 mAb to immunodeficient (NSG) mice bearing human GBM xenografts resulted in significant reduction of tumor growth and sensitization of GBM tumors to TMZ therapy.”
In regards to the argument that the impact of anti-ABCB5 antibody and TMZ is unpredictable because chemosensitization of tumors is highly unpredictable and in the absence of data demonstrating that the combination of anti-ABCB5 antibody and TMZ together function better than when administered separately, Banerjee et al teaches administering the monoclonal anti-ABCB5 antibody “3C2-1D12” of Frank et al to subjects with GBM reduces tumor growth and sensitizes GBMs to TMZ therapy (Abstract, in particular).
In regards to the citation of Ko et al (Cancer Cell Int, 2015, 15:71) and indication the claims are non-obvious because until the combination of anti-ABCB5 antibody and TMZ is tested in vivo, the results are unpredictable because effectiveness of the agents requires that both agents are properly delivered to the correct site of action, function in vivo, and do not interfere with the activity of one another: Banerjee et al tested the combination of anti-ABCB5 antibody and TMZ in vivo (Abstract).
In regards to the statement that the in vivo data presented in Banerjee et al shows an anti-ABCB5 antibody slowed tumor growth in immunodeficient NSG mice bearing human GBM xenografts and that Example 4 of the instant specification demonstrated an in vivo model that administration of anti-ABCB5 antibodies and Temozolomide (TMZ) resulted in significant decreases in tumor volume relative to the administration of antibody alone and that a skilled artisan would not have had a reasonable expectation of success without such data, the Banerjee et al Abstract teaches “in vivo systemic administration of anti-ABCB5 mAb to immunodeficient (NSG) mice bearing human GBM xenografts resulted in significant reduction of tumor growth and sensitization of GBM tumors to TMZ therapy.” Further, as disclosed at the first full paragraph on page 33 of the instant specification, the in vivo model disclosed by Example 4 of the instant specification also uses immunodeficient NSG mice bearing human GBM xenografts.
In regards to the argument that the skilled artisan would not have predicted in view of Banerjee et al and Frank et al that an antibody conjugated to a therapeutic agent would function to enhance TMZ activity, the examiner disagrees. Banerjee et al teaches administering the monoclonal anti-ABCB5 antibody “3C2-1D12” of the combined method to subjects with GBM reduces tumor growth and sensitizes GBMs to TMZ therapy (Abstract, in particular).
The examiner agrees that the provided new data in the Declaration of Natasha Frank showing a human anti-ABCB5 antibody conjugated to a therapeutic agent in an orthotopic GBM model supports the claimed method (and the combined method) treats GBMs
Claim Rejections - 35 USC § 112
Claims 3 and 8 remain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a NEW MATTER rejection.
Claim 3 recites methods of administering to a subject having a cancer TMZ and an ABCB5 antibody that is conjugated to a therapeutic agent. Descriptions of methods of administering to a subject having a cancer TMZ and an ABCB5 antibody that “is conjugated to a therapeutic agent” are not found in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventors, at the time the invention was filed, had possession of the claimed invention.
Response to Arguments
In the Reply of 7/15/26, Applicant argues the use of an ABCB5 antibody conjugated to a therapeutic agent, with or without chemotherapy treatment are support in the specification. Applicant further cites the following as support for the claimed methods:
“On page 2 in the Summary of the Invention it is taught that "a method for treating Glioblastoma multiforme (GBM), by administering to a subject having GBM an inhibitor of ATP-binding cassette subfamily B member 5 (ABCB5) and a chemotherapeutic agent, wherein the chemotherapeutic agent is an alkylating agent in an effective amount to treat the GBM. In some embodiments, the alkylating agent is Temozolomide." It is further taught on the same page that methods are provided for "identifying a subject having a chemoresistant cancer, administering an effective amount of an ABCB5 inhibitor to reverse a chemotherapy induced G2/M arrest in cancer cells of the subject and administering a chemotherapeutic agent to the subject to promote cancer cell death." On page 13 of the patent application as filed it is taught that "In some embodiments, the ABCB5 inhibitor is an anti-ABCB5 antibody or fragment." On page 14 of the specification it is taught that "Antibody conjugates are also provided. The conjugates include any antibody of the present disclosure and an agent. The agent may be selected from a therapeutic agent, an imaging agent, a labeling agent, or an agent useful for therapeutic and/or labeling purposes."”
The amendments to the claims and the arguments found in the Reply of 7/15/26 have been carefully considered, but are not deemed persuasive. No portion of the specification cited by Applicants discloses methods of administering to a subject having a cancer TMZ and an ABCB5 antibody that is conjugated to a therapeutic agent. The only mention of ABCB5 antibody “conjugated to a therapeutic agent” in the instant specification is at page 14: "Antibody conjugates are also provided. The conjugates include any antibody of the present disclosure and an agent. The agent may be selected from a therapeutic agent, an imaging agent, a labeling agent, or an agent useful for therapeutic and/or labeling purposes." However, page 14 does not disclose methods of administering to a subject having a cancer TMZ and an ABCB5 antibody that is conjugated to a therapeutic agent.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
Claim 12 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 12 is rejected for reciting “The method of claim 4, wherein the anti-ABCB5 antibody…” Claim 4 has been cancelled by Applicant. The metes-and-bounds of claim 12 are unclear because it is unclear which method claim 12 is further limiting.
Conclusion
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/SEAN E AEDER/Primary Examiner, Art Unit 1642
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