DETAILED ACTION
This office action is in response to applicant’s filing dated December 2, 2024.
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 .
Status of Claims
Claims 36-55 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed December 2, 2024. Acknowledgement is made of Applicant's cancelation of claims 1-35; and addition of new claims 36-55.
Priority
The present application is a Continuation of US Application No. 17/375,796 filed on July 14, 2021, which is a Continuation of US Application No. 15/487,263 filed on April 13, 2017, which claims benefit of US Provisional Application No. 62/322,079 filed on April 13, 2016.
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 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.
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 36-49 and 51-53 are rejected under 35 U.S.C. 103 as being unpatentable over Zucker et al (US 2015/0080460 A1) in view of Szabo et al (Brain Research, 1999, 840:92-98).
Regarding claims 36 and 41-47, Zucker teaches a method of treating hypertension comprising administering an effective amount of RTX (resiniferatoxin) intrathecally to the T1-T4 region of the spinal column (claim 10) wherein the RTX is administered to a human (claim 14). T1-T4 region of the spinal column reads on first through fourth thoracic vertebral level. Hypertension by broadest reasonable interpretation means high blood pressure. Thus, treating hypertension reads on decreasing blood pressure in a subject with high blood pressure.
Zucker does not teach RTX is administered to an epidural space.
However, Szabo teaches to reduce side effects of treatment, intrathecal and epidural routes of administration have been used where appropriate to reduce the total dose of agent administered while achieving regional control (abstract); resiniferatoxin (RTX) is an ultrapotent capsaicin analog (abstract); well-defined pharmacological advantages of epidural administration include anatomical proximity to the targeted tissue and low systemic uptake (page 93, left, 3rd paragraph); although the effectiveness of capsaicin remains unresolved in animal models, epidural capsaicin has been found to produce profound, long-lasting effect in the rat (page 93, left, 3rd paragraph) and epidurally administered RTX produces profound, long-term effect in the rat (page 93, left, 3rd paragraph).
As such, since Zucker teaches a method of treating hypertension comprising administering an effective amount of RTX (resiniferatoxin) intrathecally to the T1-T4 region of the spinal column wherein the patient is human, and since Szabo teaches intrathecal and epidural routes of administration are used to reduce the total dose of an agent while achieving regional control and epidurally administered RTX produces profound, long-term effects, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to administer RTX epidurally with an expectation of success, since the prior art establishes that epidural and intrathecal routes of administration are both utilized to reduce total dose of agent administered while achieving regional control and epidurally administered RTX produces profound, long-term effects.
Regarding the wherein limitations of instant claims 36, 41, and 51-53, the wherein limitations of these claims, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).).
Regarding claim 37, the prior art is silent regarding "decreasing systolic blood pressure." Similarly, regarding claim 38, the prior art is silent regarding "decreasing diastolic blood pressure." However, high systolic or high diastolic blood pressure are species of hypertension. As such, the skilled in the art will be further motivated to treat hypertension the subgroup of hypertension patients that suffer from high systolic or high diastolic blood pressure, since it is expected that this subgroup of hypertension (that also suffer from high systolic or high diastolic blood pressure) will also benefit from this treatment (the administration of resiniferatoxin) that is known to be effective to the larger genus of hypertension patients in general.
Although the prior art is silent regarding “decreasing systolic blood pressure and/or diastolic blood pressure,” decreasing systolic blood pressure and/or diastolic blood pressure" will naturally flow from the teachings of (or method made obvious by) the prior art (see above rejection), since the same compound (resiniferatoxin) is being administered to the same subjects (subjects suffering from hypertension). In other words, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. Apparently, Applicant has discovered a new property or advantage of the method made obvious by the prior art. MPEP 2145 II states: “The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art, cannot be the basis for patentability when the differences would otherwise be obvious” Ex parte Obiaya, 227 USPQ 58,60.
Taken together, all this would result in the practice of the method of claims 36-38, 41-47, and 51-53 with a reasonable expectation of success.
Regarding claims 39, 40, 48, and 49, Zucker teaches a method of treating hypertension comprising administering an effective mount of RTX intrathecally to the T1-T4 region of the spinal column (claim 10) wherein the concentration of RTX administered is from about 100 ng/ml to about 500 µg/ml (claim 11), which is equivalent to 0.1 µg/ml to about 500 µg/ml; wherein the concentration of RTX administered is from about 5 µg/ml to about 80 µg/ml (claim 12); and wherein the concentration of RTX is administered is from about 20 µg/ml to about 60 µg/ml (claim 13). MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Taken together, all this would result in the practice of the method of claims 39, 40, 48, and 49 with a reasonable expectation of success.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Zucker et al (US 2015/0080460 A1) in view of Szabo et al (Brain Research, 1999, 840:92-9) as applied to claims 36-49 and 51-53 above, and further in view of Ipe et al (Indian J Anaesth, 2010; 54(3): 205–209, pp. 1-13).
Regarding claim 28, Zucker teaches for intrathecal administration an amount from about 0.5 to 5 mL, often 3 ccs are injected; the total amount of RTX in the injected volume is usually from about 500 nanograms to about 500 micrograms [0037]; the preferred dose for an adult human is about 25 µg of RTX for intrathecal administration and the volume administered for intrathecal administration is from about 0.5 ml to about 4.0 mL [0038].
Ipe teaches a comparative study of intrathecal and epidural buprenorphine using combined spinal-epidural technique for caesarean section (title) and a single space Combined Spinal Epidural technique was chosen and the same volume of drug was injected intrathecally and epidurally in all study groups (page 2, 5th paragraph). Ipe establishes that it was known in the art that the same volume of drug can be injected intrathecally and epidurally.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to utilize the volume of administration of resiniferatoxin taught by Zucker as a starting point for optimizing the volume of resiniferatoxin to administer in a method of treating hypertension comprising administering an effective amount of RTX (resiniferatoxin) to an epidural space with an expectation of success, since the prior art teaches the same volume of drug can be injected intrathecally and epidurally.
MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Taken together, all this would result in the practice of the method of claim 50 with a reasonable expectation of success.
Claims 54 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Zucker et al (US 2015/0080460 A1) in view of Szabo et al (Brain Research, 1999, 840:92-9) as applied to claims 36-49 and 51-53 above, and further in view of Barbosa et al (J Physiol, 2016; 594: 715-725, published December 12, 2015).
Zucker and Szabo teach all the limitations of claims 54 and 55, except wherein the method comprises administering an opioid.
However, Barbosa teaches in clinical exercise tests using a treadmill, an abnormal increase of BP (blood pressure) in HT (hypertensive) patients was detected during the first 6 min of exercise; BP abnormally rises since the first minute of leg cycling exercise in HT patients; intrathecal fentanyl normalized the increase of BP during cycling in HT men (page 719, right, last bridge paragraph). Fentanyl reads on an opioid. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the method of treating hypertension comprising administering an effective amount of RTX (resiniferatoxin) to further administer the opioid, fentanyl, to treat hypertension in subjects that exercise with a reasonable expectation of success, since the prior art teaches fentanyl reduces blood pressure in hypertensive subjects that exercise.
Taken together, all this would result in the practice of the method of claims 54 and 55 with a reasonable expectation of success.
Conclusion
Claims 36-55 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
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