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
Status of Application
1. Receipt of the Request for Continued Examination (RCE) under 37 C.F.R. 1.114 and Applicants’ Arguments/Remarks, all filed 17 August 2026 are acknowledged.
Claims 1-2, 5-6, 27-28, 33-34, 37, 39-41, and 55-57 are currently pending. Claims 3-4, 7-26, 29-32, 35-36, 38, and 42-54 are cancelled. Claims 55-57 are newly added. Claims 1, 27, and 33 are amended. Claims 1-2, 5-6, 27-28, 33-34, 37, 39-41, and 55-57 are examined on the merits within.
Continued Examination Under 37 C.F.R. 1.114
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 17 August 2026 has been entered.
Withdrawn Rejections
3. Applicant’s arguments, filed 17 August 2026, with respect to the 35 U.S.C. 103 Rejections of Devries et al. in view of Marambaud have been fully considered and are persuasive. The 35 U.S.C. 103 Rejections of claims 1-2, 6, 27-28, 33-34 and 37-41 have been withdrawn in view of the claim amendments.
New Rejections
Claim Rejections – 35 U.S.C. 103
4. 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.
5. Claim(s) 1-2, 6, 27-28, 33-34, 37, 39-41, and 55-57 is/are rejected under 35 U.S.C. 103 as being unpatentable over Parambil et al. (Laryngoscope, 2018) in view of Marambaud (WO2020/068719).
Parambil et al. teach a patient with hereditary hemorrhagic telangiectasia dependent on iron infusion and packed red blood cell transfusions. The patient is administered 100 mg of pazopanib with dramatic improvements in epistaxis and normalization of hemoglobin and iron levels without replenishment needs for 12 months. See abstract. The initial dose of pazopanib was 50 mg daily which was increased to 100 mg daily and continued with this dose through 6 months and 1 year. See page 2235. Side effects are observed in approximately 30% of patients when prescribed pazopanib at a standard dose of 800 mg daily. At a low dose of 100 mg, pazopanib is well tolerated without side effects. See page 2236
Parambil et al. do not teach hemorrhagic locus, vascular density, or cardiac failure.
Marambaud teaches compositions for treating vascular lesions and hereditary hemorrhagic telangiectasia. See abstract. Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease or syndrome, is a hemorrhagic genetic disorder that leads to abnormal blood vessel formations (or vascular lesions), including prominently telangiectasis and arteriovenous malformations, in the skin, mucous membranes and organs, such as the liver, lung, gastrointestinal system, and brain of an afflicted subject. In its most severe manifestations, HHT can lead to highly debilitating and life-threatening events, such as severe epistaxis and internal bleeding. HHT is also associated with secondary complications, which include anemia, cerebral abscess and embolism following pulmonary AVMs, as well as high-output cardiac failure consecutive to liver AVMs. See paragraph [0004]. Active ingredients include pazopanib. See paragraph [0015]. Receptor tyrosine kinase (RTK) inhibitors treat a vascular lesion and/or bleeding and/or anemia in a subject. See paragraph [0006]. Figures 1A-1B show the effects of different treatments on number and diameter of arteriovenous malformations (AVMs), diameter of veins, and vascular density, including statistical comparisons. See paragraph [0008].
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to identify a hemorrhagic locus prior to administering pazopanib in an effective amount because Parambil et al. teach treatment of hereditary hemorrhagic telangiectasia with pazopanib and Marambaud teaches that receptor tyrosine kinase inhibitors treat vascular lesions and/or bleeding in subjects with hereditary hemorrhagic telangiectasia. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to determine a first vascular density of a subject with hereditary hemorrhagic telangiectasia and administer pazopanib and then identify a second vascular density and modify the amount of pazopanib based on the results because Marambaud teaches the correlation between vascular density and hereditary hemorrhagic telangiectasia. It is well within the purview of the skilled artisan to modify dosing regimen by increasing or decreasing therapeutic amounts based on routine testing to determine the efficacy of the therapeutic agent, especially since it is known to give up to 800 mg pazopanib daily. It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to determine a cardiac failure in a subject prior to administering pazopanib in an effective amount because Marambaud teaches the correlation between hereditary hemorrhagic telangiectasia and cardiac failure including anemia, lung lesions and liver lesions.
6. Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Parambil et al. (Laryngoscope, 2018) in view of Marambaud (WO2020/068719) as applied to claims 1-2, 6, 27-28, 33-34, 37, 39-41, and 55-57 above and further in view of Beckman et al. (Orphanet Journal of Rare Diseases, 2020).
Parambil et al. and Marambaud do not teach severity indicators.
Beckman et al. teach Hereditary Hemorrhagic Telangiectasia (HHT) is a rare inherited disorder characterized by development of mucocutaneous telangiectasis and visceral organ arteriovenous malformations, which can lead to recurrent, spontaneous bleeding and development of iron deficiency anemia. The primary objective of this study was to ascertain the relationship between epistaxis severity scores (ESS), laboratory values, genotype, and phenotype in HHT. Our secondary objective was to assess efficacy of systemic antifibrinolytic therapy in reducing ESS in HHT. See abstract. We demonstrate that the ESS predicts markers of iron deficiency anemia and that it can be used to both guide and monitor response to therapeutic interventions in patients with HHT. See Conclusion.
It would have been obvious to one of ordinary skill in the art as of the effective filing date of the invention to determine the effective amount of pazopanib to administer based on severity scores because Beckman et al. teach using the knowledge learned from severity scores to guide and monitor therapeutic interventions.
Correspondence
7. No claims are allowed at this time.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA WORSHAM whose telephone number is (571)270-7434. The examiner can normally be reached Monday-Friday (8-5).
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/JESSICA WORSHAM/Primary Examiner, Art Unit 1615
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