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 .
Status
Claims 1-13 are pending and under examination. No claim amendments were included with Applicant’s recent response.
Priority
This application is a divisional of U.S. Application 18/115,058, filed February 28, 2023, which claims the benefit of priority to U.S. Provisional Application 63/268,628, filed February 28, 2022.
Information Disclosure Statement
No Information Disclosure Statement was filed with Applicant’s recent response.
Claim Rejections - 35 USC § 103
Rejection maintained
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.
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.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Hedlund et al. (USPN 5,416,078A) in view of He et al. (Neurochemistry International, Volume 125, 2019, Pages 99-110, ISSN 0197-0186, https://doi.org/10.1016/j.neuint.2019.02.010), taken in further view of Forrest et al. (US PG-PUB 20080194548 A1).
Claimed invention
A method of fluid resuscitation of a patient in need thereof, comprising: administering to the patient a resuscitation fluid and an effective amount of a C-C chemokine receptor (CCR) inhibitor.
Prior art
Hedlund teaches the use of deferoxamine (DFO) and a water-soluble biopolymer formulated as an aqueous solution for use as fluid resuscitation. See abstract. The fluid resuscitation can be used for ameliorating systemic oxidant injury occurring during ischemia and subsequent reperfusion. The fluid resuscitation may be indicated in treatment of burn injury, lung injury caused by inhalation of hot and/or toxic substances, such as smoke derived from combustion, hemorrhagic shock and other types of trauma. See abstract. Lactated Ringers solution can be combined with the DFO-polymer agent to form the resuscitation fluid for use in ameliorating systemic oxidant injury during ischemia and subsequent reperfusion in a subject.
Hedlund does not expressly teach a CCR2 antagonist, such as, INCB3284.
However, CCR2 inhibition is disclosed as useful for downregulating pro-inflammatory factors and benefitting in treatment of ischemic stroke. See He, abstract, p. 106, 1st col. CCR2 inhibition attenuates reperfusion injury. See He, title, abstract. A specific CCR2 inhibitor was disclosed to reduce infarct size in the brain. See He, Id. CCR2 inhibition improved tissue repair and recovery after MCAO through STAT1 pathway. See He, p. 106, 2nd col. He suggests targeting CCR2 for stroke treatment.
Forrest teaches CCR2 antagonists are useful for treating inflammatory disorders including reperfusion injury. INCB3284 is exemplary of the CCR2 antagonist disclosed. See Forrest, Claims 1, 4, 11 and 13; See also 0031.
A person of ordinary skill in the art (POSA) would have found it obvious to combine a CCR2 antagonist such as INCB3284 with the Lactated Ringer’s solution treatment for systemic oxidant injury occurring during ischemia and subsequent reperfusion because Hedlund teaches a resuscitation fluid containing Ringer’s solution and deferoxamine (DFO) and a water-soluble biopolymer for treating systemic oxidant injury occurring during ischemia an subsequent reperfusion, while He teaches CCR2 inhibition is useful for downregulating pro-inflammatory factors, benefitting in treatment of ischemic stroke and attenuating subsequent reperfusion injury. Given that the references address injury occurring during ischemia and subsequent reperfusion, the POSA would have had reasonably expectation of success to combine a CCR2 antagonist as taught by Forrest in the Hedlund resuscitation fluid treatment for mitigating reperfusion injury.
Claims 2-5 limit claim 1, wherein the patient is experiencing one of several possible conditions including hemorrhagic shock, surgery (cardiovascular, abdominal, transplant), ischemia, hypovolemic shock, myocardial infarction, stroke, trauma, burn, sepsis, or shock. Hedlund teaches the treatment of burn injury, lung injury caused by inhalation of hot and/or toxic substances, such as smoke derived from combustion, hemorrhagic shock surgery and other types of trauma. See abstract and Example 1.
Claim 6 limits claim 1, wherein the CCR inhibitor is a CCR2 and/or CCR3 antagonist. Claim 7 limits claim 1, wherein the CCR inhibitor is INCB3284 or SB328437.
Forrest teaches INCB3284 is a CCR2 antagonists useful for treating inflammatory disorders including reperfusion injury.
Claim 8 limits claim 1, wherein the CCR inhibitor is administered separately from the resuscitation fluid. Claim 9 limits claim 1, wherein the CCR inhibitor is administered in one or two doses. Forrest teaches ICNB3284 in a separate composition than the resuscitation fluid. Thus, a POSA would have reasonably understood that the compositions can be administered separately.
Claim 10 limits claim 1, wherein the CCR inhibitor is a component of the resuscitation fluid. While the resuscitation fluid is described separately in a different composition than the CCR2 inhibitor, a POSA would have found it obvious to combine them together to form on composition to administer simultaneously to minimize the number of administration steps.
Claim 11 limit claim 1, wherein the CCR inhibitor is administered at a dosage of from 1 to 10 mmol/kg of the patient. Forrest teaches an effective amount of the combination is that amount that will relieve the subject being treated of the symptoms of the particular condition, or prevent such symptoms, and the specific dose level and frequency of dosage may vary and will depend upon a variety of factors including the activity of the specific compounds used in combination, the metabolic stability and length of action of the compounds, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, the severity of the particular condition and the host undergoing therapy. However, dosage levels of the CCR2 antagonist on the order of about 0.001 mg/kg to about 250 mg/kg of body weight per day, typically about 0.005 to about 100 mg/kg, more particularly about 0.01 to about 50 mg/kg and especially about 0.05 to about 10 mg/kg per day are useful in the novel method of treatment. Dosage levels of the statin of about 0.1 to 500 mg/kg of body weight per day, typically about 0.5 to about 250 mg/kg, more particularly about 5 to about 100 mg/kg and especially about 5 to about 50 mg/kg of body weight per day are useful in the novel method of this invention. Thus, a POSA would understand the amount would vary in order to optimize treatment of the subject. Accordingly, the POSA would have found the claimed dose to be obvious.
Claim 12 limits claim 1, wherein the resuscitation fluid is lactated Ringer's solution. Hedlund teaches Lactated Ringer’s solution.
Claim 13 limits claim 1, wherein the resuscitation fluid is administered in an amount that is less than three times the amount of fluid lost by the patient. It is well-known that the resuscitation fluid is administered in an amount that is less than three times the amount of fluid loss as evidenced by the specification at bottom of p. 10.
Response to arguments
Applicant's arguments have been fully considered but have not been found to be persuasive.
Applicant argues that Hedlund is concerned with oxidative injury caused by radical species rather than pro-inflammatory factors and therefore provides no motivation to combine with CCR inhibitors. However, Hedlund expressly teaches the treatment of ischemia and subsequent reperfusion injury using resuscitation fluids (see abstract). Hedlund further teaches that the resuscitation fluid is useful for ameliorating systemic oxidant injury occurring during ischemia and subsequent reperfusion. He teaches that CCR2 inhibition reduces reperfusion injury and improves tissue recovery occurring following ischemia injury. Because both Hedlund and He address reperfusion injury following ischemia, a person of ordinary skill in the art would have found it obvious to combine the teachings in order to further mitigate reperfusion injury.
Applicant argues that the deferoxamine (DFO) of Hedlund would interact with the germanium-containing compound propagermanium used in He, thereby preventing a reasonable expectation of success. However, the rejection does not rely on propagermanium as the CCR inhibitor. Rather, Forrest teaches CCR2 antagonists including INCB3284 for treating inflammatory conditions including reperfusion injury. Applicant has not provided evidence demonstrating that deferoxamine would chemically inactivate such CCR antagonists or otherwise prevent therapeutic activity. Applicant’s speculation regarding possible interactions are insufficient to rebut the obviousness rejection.
Applicant argues that the present invention obtains a synergistic blood pressure-regulating effect between the CCR inhibitor and the resuscitation fluid. However, the evidence is not commensurate in scope with the claims. The claims broadly encompass administration of any CCR inhibitor with any resuscitation fluid, whereas the data are limited to particular CCR antagonists (INCB3284 and SB328437) administered with lactated Ringer’s solution. Additionally, the data compare lactated Ringer’s solution alone with lactated Ringer’s solution plus a CCR inhibitor rather than comparing the claimed method with the closest prior art treatment disclosed by Hedlund. Accordingly, the evidenced proffered to demonstrate unexpected results sufficient to overcome the prima facie case of obviousness.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622