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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-14 in the reply filed on 08/10/2026 is acknowledged.
Claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/10/2026.
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.
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.
Claim(s) 11-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maher (Mol Cancer Ther 6(2):732-741 (2007)).
Maher disclosed (abstract): “Hypoxic regions within solid tumors harbor cells that are resistant to standard chemotherapy and radiotherapy. Because oxygen is required to produce ATP by oxidative phosphorylation, under hypoxia, cells rely more on glycolysis to generate ATP and are thereby sensitive to 2-deoxy-D-glucose (2-DG), an inhibitor of this pathway. Universally, cells respond to lowered oxygen tension by increasing the amount of glycolytic enzymes and glucose transporters via the wel characterized hypoxia-inducible factor-1 (HIF).”
Maher found that HIF-1α expression correlated with reduced sensitivity to 2-DG in hypoxic osteosarcoma cells (first section of results and Fig. 1).
Maher found that treating cells with siRNA to suppress HIF-1α expression under hypoxic conditions decreased resistance to 2-DG (second section of results and Fig. 2).
Maher concluded (last paragraph, page 740): “From the results in this study, it is clear that HIF plays an important role in decreasing the effectiveness of 2-DG in cells under hypoxia. Thus, inhibition of this factor may increase its clinical efficacy…Combining such inhibitors of HIF with 2-DG may be a more effective strategy than either agent alone, particularly for targeting the slow growing hypoxic cell populations found in most solid tumors.”
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to treat solid tumors with a combination of 2-DG and a HIF-1α inhibitor as recited in claims 11-13.
Claim(s) 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Maher (Mol Cancer Ther 6(2):732-741 (2007)) in view of Dewhirst (US 2014/0249097).
Maher disclosed (abstract): “Hypoxic regions within solid tumors harbor cells that are resistant to standard chemotherapy and radiotherapy. Because oxygen is required to produce ATP by oxidative phosphorylation, under hypoxia, cells rely more on glycolysis to generate ATP and are thereby sensitive to 2-deoxy-D-glucose (2-DG), an inhibitor of this pathway. Universally, cells respond to lowered oxygen tension by increasing the amount of glycolytic enzymes and glucose transporters via the wel characterized hypoxia-inducible factor-1 (HIF).”
Maher found that HIF-1α expression correlated with reduced sensitivity to 2-DG in hypoxic osteosarcoma cells (first section of results and Fig. 1).
Maher found that treating cells with siRNA to suppress HIF-1α expression under hypoxic conditions decreased resistance to 2-DG (second section of results and Fig. 2).
Maher concluded (last paragraph, page 740): “From the results in this study, it is clear that HIF plays an important role in decreasing the effectiveness of 2-DG in cells under hypoxia. Thus, inhibition of this factor may increase its clinical efficacy…Combining such inhibitors of HIF with 2-DG may be a more effective strategy than either agent alone, particularly for targeting the slow growing hypoxic cell populations found in most solid tumors.”
Maher did not suggest comparing expression levels of HIF-1α between tumor and healthy tissue as recited in claim 1.
Dewhirst disclosed (paragraph [0333], citations omitted): “There has been intense interest in developing novel therapeutic strategies to target HIF-1α in cancer therapy for three main reasons. First, HIF-la expression has been found in the majority of solid tumors, while it is usually absent in normal tissues. This is because hypoxia, which is a characteristic feature of solid tumors, stabilizes HIF-1α in tumor cells. The differential expression and distribution of HIF-1α between normal tissues and tumors allow the inhibition of HIF-1α to target tumor cells, while sparing normal tissues.”
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to predict that a HIF-1α inhibitor would have benefit in solid tumors being treated with 2-DG based on Maher’s disclosed mechanism by which HIF-1α expression correlated with resistance to 2-DG, and it would have been similarly obvious that HIF-1α inhibitors would have conferred benefit in tumors expressing HIF-1α compared to normal tissues based on the teachings of Dewhirst. It would therefore have been obvious to measure HIF-1α expression in tumor cells and treat with a HIF-1α inhibitor along with 2-DG in cases where HIF-1α expression was higher in the tumor than in corresponding normal tissue.
Claim(s) 5-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maher (Mol Cancer Ther 6(2):732-741 (2007)) in view of Dewhirst (US 2014/0249097) as applied to claims 1-4 above, and further in view of Weber (US 2026/0035403).
The teachings of Maher and Dewhirst have been discussed.
Weber taught (paragraph [0099]): “The expression level of the biomarker can be measured, for example, by detecting the protein or RNA, e.g., mRNA, level of the biomarker.”
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application when practicing the method suggested by the combined disclosures of Maher and Dewhirst to measure either at the level of mRNA or protein, as this was commonly known in the art when measuring levels of biomarkers as taught by Weber.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/ Primary Examiner, Art Unit 1681
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