DETAILED ACTION
Claims 1, 3, 6-11, 14, 16, 19-24 and 29 are currently pending and under examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/17/2025 has been entered.
Withdrawn Rejections
The prior rejection of claims 1, 6-11, 14, 16, 18-24 and 29 under 112(b) are withdrawn based on Applicant’s claim amendments to clarify two doses and the time of administration of the second dose.
The prior rejection of claims 4 and 18-19 under 112(d) is withdrawn based on Applicant canceling claims 4 and 18 and amending claim 19 to time frame in instant claim 1.
Examiner’s Note
Applicant's amendments and arguments filed 09/17/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 09/17/2025, it is noted that claims 1, 9, 19, 22 and 29 have been amended and no new matter or claims have been added.
Modified Rejections:
The following rejections are modified based on Applicant’s claim amendment.
Claim Objections
Claims 1 and 29 are objected to because of the following informalities: Claims 1 and 29 recite “wherein the pharmaceutical composition is administered to the patient before the patient is subjected to the stress, wherein at least two doses of the pharmaceutical composition is administered to the patient before the subject is subjected to stress”. The limitation of administration before the patient is subjected to stress is repetitive language. Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 20 and 22 are 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 3 is directed to two doses being administered between 12h and 48 hours before the patient is subjected to stress. Instant claim 1 requires the second does to be between 8 and 2 hours before the patent is subjected to stress. It is unclear how two doses are administered between 12 and 48 hours and additionally the second dose is administered between 8 and 2 hours before. Thus the instant claims have unclear metes and bounds.
Claims 20 and 22 are dependent on canceled claim 4 and thus unclear scope as they are deponent on a canceled claim. For examination purposes claims 20 and 22 will be examined as deponent on independent claim 1.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3 and 8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 is directed to two doses being administered between 12h and 48 hours before the patient is subjected to stress. Instant claim 1 requires the second does to be between 8 and 2 hours before the patent is subjected to stress. It is unclear how two doses are administered between 12 and 48 hours and additionally the second dose is administered between 8 and 2 hours before. Thus, instant claim 3 does not further limit the dosing timing required by instant claim 1.
Claim 8 is directed to at least one dose being administered between 96 and 1 hour before the patent is subjected to stress. Instant claim 1 requires two doses to be administered in the time period of claim 8, and thus claim 8 is not further limiting instant claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claim(s) 1, 3, 6-10, 16, 19-20, 22-24 and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0072647 (Applicant provided 01/13/2023) in view WO 01/45716 (Applicant provided 01/13/2023) and US 2015/0150836 (Applicant provided 01/13/2023).
Regarding claims 1 and 29, the limitation of a method for the prevention or reduction of stress-induced metabolic derangement in a patient subjected to stress, the method comprising administering to the patient a pharmaceutical composition comprising a physiologically acceptable organic and/or inorganic vanadium compound or complex and further comprising a pharmaceutically acceptable excipient is met by the ‘647 publication teaching a method for maintaining normoglycemia in a mammal in need thereof, preferably a critically ill patient suffering from acute stress (abstract). A high portion of patients suffering from acute stress develop hyperglycemia [0002]. Thus use of vanadium compounds in controlling hyperglycemia in diabetic patients is known in the art [0013]. The composition is taught to comprise a physiologically acceptable organic and/or inorganic vanadium compound or complex administered to said mammal ([0016], [0034]) a pharmaceutically acceptable carrier [0050]. Maintaining normoglycemia would read on preventing or reduction in hyperglycemia, a type of metabolic derangement per instant claim 5.
Regarding claim 5, the limitation of wherein the metabolic derangement comprises hyperglycemia is met by the ‘647 publication teaching maintaining normoglycermia (abstract). Maintaining normoglycemia would read on preventing or reduction in hyperglycemia, the elected metabolic derangement.
Regarding claim 6, the limitation of wherein the physiologically acceptable organic and/or inorganic vanadium compound or complex is bis(maltolato)oxidovandium (BMOV) is met by the ‘647 publication teaching BMOV (claim 45).
Regarding claim 7, the limitation of wherein BMOV is the sole active pharmaceutical ingredient is met by the ‘647 publication teaches BMOV being the only tested active ingredient in the composition [0067].
Regarding claim 9, the limitation of wherein the stress is trauma is met by the ‘647 publication teaching the stress is acute stress caused by trauma [0042].
Regarding claim 10, the limitation of wherein the composition is administered intravenously is met by the ‘647 publication teaching intravenously administration [0055].
Regarding claim 16, the limitation of wherein a dose of pharmaceutical composition comprises between 0.01 mg and 30 mg of vanadium compound per kg body weight of the patient is met by the ‘647 publication teaches 7 mg /kg and 15 mg/kg [0067].
Regarding claim 20, the limitation of wherein the pharmaceutical composition is provided as an aqueous solution and wherein the dose of the pharmaceutical composition comprises between about 0.01 mg and 30 mg of vanadium compound or complex per body weight of the patient is met by the ‘647 publication teaching 7 mg /kg and 15 mg/kg [0067] and the ‘372 publication teaching phosphate buffered saline [0046].
Regarding claim 22, the limitation of wherein the stress to which the patient is subjected to is trauma is met by the ‘647 publication teaching acute stress caused by trauma (claim 34).
Regarding claims 23-24, the limitations of the increase in glucose content in the blood of a patient during specific time period compared to a time point before the patient is subjected to stress is an inherent feature in the ‘647 publication as the ‘647 publication teaches the method of administered the claimed composition to the patient subjected to stress, thus the compositions, active step and patient population are taught and therefore must result in the claimed glucose content. In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functional that are newly cited or is identical to a product instant claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristics relied on" (205 USPQ 594, second column, first full paragraph).
The ‘647 publication does not specifically teach administration to a patient before the patient is subjected to stress (claims 1 and 29), at least one at a time point between 12 h and 48 h before the patient is subjected to stress (claim 3, 8).
The ‘647 publication does not specifically teach wherein at least two doses (claim 1, 29) of the composition is administered to the patient wherein the first single dose is administered between 96 h and 10 h before the patient is subjected to stress and a second single dose is administered between 8 h and 0 h before the patient is subjected to stress (claim 1 and 29), first dose between 96 h and 10 h, second dose between 8 and 2h and third does administered when the patient is subjected to stress (claim 19).
The ‘716 publication teaches a pharmaceutical composition for the prophylactic treatment of secondary injury of tissue, said secondary injury being induced by primary injury of mainly surrounding tissue and being the result of traumatic event. The composition includes vanadium compound administered in a single dose and preferably before or immediately or shortly after the traumatic event (abstract). The vanadium compound is taught to be preferably bis(maltolato)oxovandium (IV) (page 9, lines 20-25). The ‘716 publication teaches the administration time to be preferably before or immediately or shortly after the traumatic even (abstract) wherein the administration may be at a suitable moment prior to said operation (page 7, lines 10-15), reading on claim 1 and 3. The administration time is taught to be done prior to surgery at a suitable moment and thus teaches a result effective variable and range.
The ‘836 publication teaches dysregulated blood glucose disorder such as transient hyper glycemia that is caused by trauma [0044]. The active agent may be administered intravenously [0057]. The amount of active agent is taught to be vary with the route of administration, nature of the condition being treated and the age and condition of the patient and will ultimately be at the discretion of the attendant physical or clinician [0068]. The suitable dose is general be 10 to 75 mg/kg [0069]. The desired dose may be conveniently be presented in a single dose or as a divided doses administered at appropriate interval for example as two, three, four or more sub doses per day [0071].
That being said and in lieu of objective evidence of unexpected results, the administration time can be viewed as a variable which achieves the recognized result of successfully treating a specific patient. The optimum or workable range of dosing can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Appellants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of dosage nonobvious.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to administer the composition comprising BMOV prior to trauma such as surgery as the ‘647 publication teaches the administration of BMOV to maintain normoglycermia in response to trauma such as surgery and the ‘716 publication teaches administering BMOV compositions prior to a traumatic event. Thus one of ordinary skill in the art before the filing date of the claimed invention would be motivated and have an expectation of success in administering a BMOV composition prior to a traumatic even such as surgery based on the teachings of the ‘647 publication and the ‘716 publication. The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983) (see MPEP 2144 (II)).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention that multiple doses within a 24 hour period prior to trauma may be used to treat hyperglycemia using the formulation of the ’647 publication because the ‘836 publication teaches that doses of active agent to treat hyperglycemia may be split into two or more doses and administered in 24 hours. One of ordinary skill in the art would have a prima facie obvious expectation of success as the ‘647 publication teaches intravenous administration before stress is applied and the ‘836 publication teaches it is known to split treatment into multiple doses and further teaches that the administration of the active agent is an optimizable parameter determined by the attendant physical or clinician.
That being said and in lieu of objective evidence of unexpected results, the dosage timing can be viewed as a variable which achieves the recognized result of successfully treating a specific patient. The optimum or workable range of dosing can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Appellants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of dosage nonobvious.
Claims 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0072647, WO 01/45716 and US 2015/0150836 as applied to claims 1, 3, 6-10, 16, 19-20, 22-24 and 29 and in further view of US 6,232,340 (previously applied).
As mentioned in the above 102(a)(1) rejection, all the limitations of claims 1, 3, 6-10, 16, 19-20, 22-24 and 29 are taught by the ‘647 publication, the ‘716 publication and the ‘836 patent.
The ‘716 publication teaches administration being oral (page 7, lines 1-10).
The combination of references does not specifically teach wherein the pharmaceutical composition is provided as a capsule, a tablet, a pill or water-soluble powder for oral administration (claim 14).
The ‘340 patent teaches vanadium complexes are provided and may be formulated into a pharmaceutical composition. The complexes or compositions may be used in the treatment of a variety of disease states including treatment of diabetes (abstract). Administration may be parenteral, intravenous or may take the form of tablet being a single dosage or multiple dosage units (column 8, lines 34-50). Solid dosage form in the form of a pressed tablet is taught (column 9, lines 1-30).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use the vanadium compound in the form of a tablet as the ‘716 publication teaches the use of vanadium compounds to be administered orally and the ‘340 patent specifically teaches and oral form to be a tablet. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘340 publication teaches multiple administration forms are known to be used for vanadium compounds including intravenous and oral forms such as tablets and the ‘647 publication teaches intravenous dosing, thus teaching it would be obvious to use known forms of administration interchangeable for the process of the ‘647 publication and the ‘716 publication to administer a vanadium compound including intravenously and orally.
Claims 11 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0072647, WO 01/45716 and US 2015/0150836 as applied to claims 1, 3, 6-10, 16, 19-20, 22-24 and 29 and in further view of US 6,268,357 (Applicant provided 01/13/2023) and US 2009/0317372 (Applicant provided 01/13/2023).
As mentioned in the above 102(a)(1) rejection, all the limitations of claims 1, 3, 6-10, 16, 19-20, 22-24 and 29 are taught by the ‘647 publication, the ‘716 publication and the ‘836 patent.
Regarding claim 21, the limitation of the composition comprises between about 0.01 mg and 30 mg per kg body weight of a patient, wherein administering a dose of the pharmaceutical composition provides for a plasma exposure level of between 25 ng/ml and 2500 ng/ml elemental vanadium is met the ‘647 publication teaches 7 mg /kg and 15 mg/kg [0067] which is administered intravenously to a subject in need thereof (abstract, [0055]). The ‘647 publication teaches the claimed composition being administered at the claimed concentration by the claimed method, intravenous, and thus would result in the plasma exposure level claimed absent factual evidence to the contrary.
The ‘647 publication does not specifically teach the composition is an aqueous solution (claim 11)
The ‘357 patent teaches organic vanadium complex used to treat elevated blood glucose and related disorders (abstract). The dosage of therapeutic formulation will vary widely depending upon the nature of the disease and frequency of administration, the manner of administration (column 5, lines 1-12). Carriers are taught to be prepared as liquids (column 5, lines 15-25) and may be prepared as aqueous injections (column 5, lines 49-55). BMOV is taught to be administered in saline (column 14, lines 5-20).
The ‘372 publication teaches compounds for treatment of hyperglycemia (abstract). The compositions may be applied via intravenous delivery routes. The injectable solution may be prepared by dissolving or dispersing a suitable preparation of the compound in water or water based carrier such as phosphate buffered saline [0046].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use phosphate buffered saline for the pharmaceutically acceptable carrier taught by the ‘647 publication because the ‘357 publication teaches it is known to use saline with BMOV and the ‘372 publication teaches specifically phosphate buffered saline is a form of saline known to be used for compounds treating hypertension. One of ordinary skill in the art before the filing date of the claimed invention would have an expectation of success in using phosphate buffered saline because the ‘647 publication does not limit the carrier used and the composition is administered intravenously and the ‘372 publication teaches the use of phosphate buffered saline for intravenous administration. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘647 publication teaches administering BMOV and the ‘357 publication teaches saline is known to be used with BMOV.
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3, 7-8 and 29 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,449,204 in view of WO 01/45716 and US 2015/0150836. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and the ‘204 patent are directed to maintaining normoglycemia or preventing hyperglycemia in a patient exposed to trauma by administering BMOV as the sole active ingredient. The ‘204 patent does not specifically teach administration to the patient before the patient is subjected to trauma wherein the at least two doses of the pharmaceutical composition is administered to the patient before the patient is subjected to the stress. The ‘716 publication teaches a pharmaceutical composition for the prophylactic treatment of secondary injury of tissue, said secondary injury being induced by primary injury of mainly surrounding tissue and being the result of traumatic event. The composition include vanadium compound administered in a single dose and preferably before or immediately or shortly after the traumatic event (abstract). The vanadium compound is taught to be preferably bis(maltolato)oxovandium (IV) (page 9, lines 20-25). The ‘716 publication teaches the administration time to be preferably before or immediately or shortly after the traumatic even (abstract) wherein the administration may be at a suitable moment prior to said operation (page 7, lines 10-15), reading on claim 1 and 3. The administration time is taught to be done prior to surgery at a suitable moment and thus teaches a result effective variable and range. The ‘836 publication teaches dysregulated blood glucose disorder such as transient hyper glycemia that is caused by trauma [0044]. The active agent may be administered intravenously [0057]. The amount of active agent is taught to be vary with the route of administration, nature of the condition being treated and the age and condition of the patient and will ultimately be at the discretion of the attendant physical or clinician [0068]. The suitable dose is general be 10 to 75 mg/kg [0069]. The desired dose may be conveniently be presented in a single dose or as a divided doses administered at appropriate interval for example as two, three, four or more sub doses per day [0071].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to administer the composition comprising BMOV prior to trauma such as surgery as the ‘204 patent teaches the administration of BMOV to maintain normoglycermia in response to trauma such as surgery and the ‘716 publication teaches administering BMOV compositions prior to a traumatic event. It would have been prima obvious to one of ordinary skill before the effective filing date of the claimed invention to administer at least two doses prior to stress as the ‘836 publication teaches that doses of active agent to treat hyperglycemia may be split into two or more doses and administered in 24 hours and it is known to split treatment into multiple doses and further teaches that the administration of the active agent is an optimizable parameter determined by the attendant physical or clinician.
Claims 1, 3 and 7-8 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of US patent 11,179,401 in view of WO 01/45716 and US 2015/0150836. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and the ‘401 patent are directed to maintaining normoglycemia or preventing hyperglycemia in a patient exposed to trauma by administering BMOV as the sole active ingredient intravenously. The ‘401 patent does not specifically teach administration to the patient before the patient is subjected to trauma, wherein at least two doses of the pharmaceutical composition is administered to the patient before the patient is subjected to the stress. The ‘716 publication teaches a pharmaceutical composition for the prophylactic treatment of secondary injury of tissue, said secondary injury being induced by primary injury of mainly surrounding tissue and being the result of traumatic event. The composition include vanadium compound administered in a single dose and preferably before or immediately or shortly after the traumatic event (abstract). The vanadium compound is taught to be preferably bis(maltolato)oxovandium (IV) (page 9, lines 20-25). The ‘716 publication teaches the administration time to be preferably before or immediately or shortly after the traumatic even (abstract) wherein the administration may be at a suitable moment prior to said operation (page 7, lines 10-15), reading on claim 1 and 3. The administration time is taught to be done prior to surgery at a suitable moment and thus teaches a result effective variable and range. The ‘836 publication teaches dysregulated blood glucose disorder such as transient hyper glycemia that is caused by trauma [0044]. The active agent may be administered intravenously [0057]. The amount of active agent is taught to be vary with the route of administration, nature of the condition being treated and the age and condition of the patient and will ultimately be at the discretion of the attendant physical or clinician [0068]. The suitable dose is general be 10 to 75 mg/kg [0069]. The desired dose may be conveniently be presented in a single dose or as a divided doses administered at appropriate interval for example as two, three, four or more sub doses per day [0071].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to administer the composition comprising BMOV prior to trauma such as surgery as the ‘401 patent teaches the administration of BMOV to maintain normoglycermia in response to trauma such as surgery and the ‘716 publication teaches administering BMOV compositions prior to a traumatic event. It would have been prima obvious to one of ordinary skill before the effective filing date of the claimed invention to administer at least two doses prior to stress as the ‘836 publication teaches that doses of active agent to treat hyperglycemia may be split into two or more doses and administered in 24 hours and it is known to split treatment into multiple doses and further teaches that the administration of the active agent is an optimizable parameter determined by the attendant physical or clinician.
Claims 1, 3, 6-10 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17/508,481 (reference application) in view of WO 01/45716 and US 2015/0150836. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and the ‘481 publication are directed to maintaining normoglycemia or preventing hyperglycemia in a patient exposed to trauma by administering BMOV as the sole active ingredient intravenously. The ‘481 publication does not specifically teach administration to the patient before the patient is subjected to trauma. The ‘716 publication teaches a pharmaceutical composition for the prophylactic treatment of secondary injury of tissue, said secondary injury being induced by primary injury of mainly surrounding tissue and being the result of traumatic event. The composition include vanadium compound administered in a single dose and preferably before or immediately or shortly after the traumatic event (abstract). The vanadium compound is taught to be preferably bis(maltolato)oxovandium (IV) (page 9, lines 20-25). The ‘716 publication teaches the administration time to be preferably before or immediately or shortly after the traumatic even (abstract) wherein the administration may be at a suitable moment prior to said operation (page 7, lines 10-15), reading on claim 1 and 3. The administration time is taught to be done prior to surgery at a suitable moment and thus teaches a result effective variable and range. The ‘836 publication teaches dysregulated blood glucose disorder such as transient hyper glycemia that is caused by trauma [0044]. The active agent may be administered intravenously [0057]. The amount of active agent is taught to be vary with the route of administration, nature of the condition being treated and the age and condition of the patient and will ultimately be at the discretion of the attendant physical or clinician [0068]. The suitable dose is general be 10 to 75 mg/kg [0069]. The desired dose may be conveniently be presented in a single dose or as a divided doses administered at appropriate interval for example as two, three, four or more sub doses per day [0071].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to administer the composition comprising BMOV prior to trauma such as surgery as the ‘481 publication teaches the administration of BMOV to maintain normoglycermia in response to trauma such as surgery and the ‘716 publication teaches administering BMOV compositions prior to a traumatic event. It would have been prima obvious to one of ordinary skill before the effective filing date of the claimed invention to administer at least two doses prior to stress as the ‘836 publication teaches that doses of active agent to treat hyperglycemia may be split into two or more doses and administered in 24 hours and it is known to split treatment into multiple doses and further teaches that the administration of the active agent is an optimizable parameter determined by the attendant physical or clinician.
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
103:
Applicant argues unexpected results in the specification regarding the specific timing regimen is critical to achieving the unexpected results. The ‘647 publication teaches fundamentally different dosing approach with infusion initiated 15 minutes prior to the 30 minutes ischemia period. This teaching is directly contrary to the treatment of a claimed windows of 96-10h and 8h-2h. The ‘716 publication teaches administration before trauma but fails to teach specific timing windows. The ‘836 publication does not remedy these deficiencies with a general teaching of dived doses within a day does not suggest the specific timing windows recited int e claims as amended. The specification demonstrates unexpected results where subject receiving tow does of vanadium compound at different timepoints before stress experience only a 28% compared to 260% increase in untreated subjects.
In response, the ‘716 publication teaches bis(maltolato)oxovandium being administered before traumatic event wherein the administration may be suitable moment prior to said operation (abstract, page 7, lines 10-15). The administration time is taught to be done prior to surgery at a suitable moment and thus teaches a result effective variable and range. The ‘836 publication teaches treatment of hyper glycemia that is caused by trauma [0044] which is administered in a single dose or as dived doses administered at appropriate interval for example as two, three, four or more sub doses per day [0071]. One of ordinary skill in the art would have a prima facie obvious expectation of success as the ‘647 publication teaches intravenous administration before stress is applied and the ‘836 publication teaches it is known to split treatment into multiple doses and further teaches that the administration of the active agent is an optimizable parameter determined by the attendant physical or clinician.
That being said and in lieu of objective evidence of unexpected results, the dosage can be viewed as a variable which achieves the recognized result of successfully treating a specific patient. The optimum or workable range of dosing can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). Appellants provide no evidence of any secondary consideration such as unexpected results that would render the optimized amounts of dosage nonobvious.
Regarding the unexpected results, the data presented is not commensurate in scope with the instant claims. The data provided is the testing of a specific vanadium compound (BMOV) intravenously administered in a specific concentration at a specific time point to reduce hyperglycemia. The instant claims are more broadly directed to prevention or reduction of metabolic derangement through administration prior to the patient is subjected the stress. The instant claims are not specific for method of administration compound, the specific treatment, i.e. hyperglycemia, nor the time period which is broadly claimed and tested only a single specific two dose time period. Thus the instant claims are much broader then the provided data.
Further, the data demonstrates administering BMOV 2x results in a greater reduction in blood glucose when subjected to stress. The ‘647 publication demonstrates BMOV is known to be used to maintain normoglycemia when subjected to acute stress (abstract claim 45), wherein a broad concentration range is taught to be used. It is not considered unexpected to administer 2xt the amount of active agent and obtain a greater response, i.e. reduction in glucose rise in response to trauma. The data presented does not indicate if the addition amount of drug used results in the higher response, which would be taught by the ‘647 publication concentration range, or if it a result of the specific time period of administration. Thus the presented data is not considered persuasive.
Double Patenting:
Applicant requests the rejection be held in abeyance until indication by the Office of allowable claims in this application.
In response, Applicant has presented no substantive argument and thus the rejection is maintained for reasons of record.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613