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 .
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Although it appears as though the references at the end of the specification are provided in the IDS, dated 4/25/2024, please confirm that all of the references listed in the specification are present on an IDS.
Claim Objections
Claim 31 objected to because of the following informalities: alteplase is not a proper noun and does not need to be capitalized. Appropriate correction is required.
Claim 37 is objected to because of the following informalities: please there is no definition provided for the abbreviation “LVO,” please amend as “large vessel occlusions (LVO).” Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 42 is 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 42 is indefinite because it is unclear how the skilled artisan is supposed to know how to adjust the medication (increase, decrease, change infusion rate, etc) based upon a subject’s estimated glomerular filtration rate (eGFR). It is unclear what direction the eGFR must move to inform the artisan how to adjust the medication. There is nothing in the instant specification to suggest how the medication can be adjusted based upon any given eGFR data.
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 (i.e., changing from AIA to pre-AIA ) 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.
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 30-50 are rejected under 35 U.S.C. 103 as being unpatentable over Leufkens, et al (PGPub 2019/0262316) and Demaerschalk, et al (Stroke, 47, 581-641, 2016). Leufkens teaches methods of treating cerebral ischemia, by administering 2-iminobioitin. See paragraph [0002]. Leufkens indicates that cerebral ischemia can include acute ischemic stroke. See paragraphs [0069] [0071]. Although Leufkens does teach a combination treatment, Leufkens teaches providing hypothermia, not a fibrinolytic drug. See paragraph [0080].
Demaerschalk provides a review on the use of the fibrinolytic drug - alteplase - for the treatment of acute ischemic stroke. Demaerschalk indicates that the administration of alteplase is the standard of care for acute ischemic stroke. See page 581, entire; page 582, entire. Demaerschalk only describes alteplase administration in the acute phase of a stroke, and does not suggest combination treatments.
Based upon the cited prior art, both 2-iminobiotin and the fibrinolytic drug alteplase are known to treat acute ischemic stroke; in fact, based upon Demaerschalk, alteplase administration has been established as the standard of care for the first few hours following a stroke. See page 584, “Age Issues” section; page 585, Table 3. Although there is no explicit rationale provided in the cited references to combine the two drugs, one must consider the level of skill and knowledge of the ordinary artisan. See MPEP 2141.03. In the instant situation, the ordinary artisan would possess an MD or PhD, with specialization in stroke treatment and outcomes. The ordinary artisan would be well-aware that the fibrinolytic drug alteplase is the standard of care for acute ischemic stroke, and would be motivated to use this drug immediately. The ordinary artisan would also be aware that there are other drugs, like 2-iminobiotin, that are useful in treating acute ischemic stroke. As such, the ordinary artisan would be implicitly motivated to combine prior art elements, using known methods, and arrive at a predictable result. See MPEP 2143(I)(A). There would be a reasonable expectation that the combination of two known acute ischemic stroke medications would provide for improved results over the use of any individual drug.
With respect to claims 30 and 31, Leufkens teaches providing 2-iminobiotin to a stroke victim, while Demaerschalk indicates that providing the fibrinolytic drug alteplase, is the standard of care for stroke victims. Combining two drugs known to treat stroke would provide for a reasonable expectation for improved results over each drug, individually.
With respect to claims 32 and 34, Demaerschalk indicates that thrombectomies are always a consideration for occlusions of a particular size. See page 604, left column, “History of Intracranial/Spinal Surgery Within 3 Months” section, 3rd paragraph. Since neither reference provides specific exclusions to the use eligibly of thrombectomies, and includes all “acute ischemic stroke,” the ordinary artisan (see above) would wholly comprehend this scenario.
With respect to claim 33, neither reference provides an exclusion on the cause of acute ischemic stroke, and as such, there would be a reasonable expectation of success on any stroke defined as acute ischemic stroke, regardless of where the occlusion occurs.
With respect to claim 35, since both induvial treatments are used to re-perfuse ischemic brain tissue, there would be a reasonable expectation that the combination of drugs would also cause re-perfusion of the ischemic brain tissue.
With respect to claim 36, Leufkens suggests that the 2-iminobiotin can be administered within the first 24 hours of the injury. See paragraph [0076].
With respect to claim 37, Leufkens teaches 6 hours, but does not does not describe a diagnosis due to large vessel occlusion. See paragraph [0076]. However, since there are no restrictions or exceptions on the administration of 2-iminobiotin, in Leufkens, there would be a reasonable expectation that any acute ischemic stroke can be similarly treated.
With respect to claim 38, Leufkens teaches 2 hours following the injury or injury causing event, further indicates that administration continues “until the individual is no longer judged to be at risk,” and also suggests following surgery. See paragraph [0076] [0077]. Based upon the fact that Demaerschalk indicates that thrombectomies are routine for certain types of acute ischemic strokes, and the fact that Leufkens indicates within 2 hours of injury, wherein “injury” is interpreted as medical interventions, like thrombectomies, would suggest that the ordinary artisan would find the claimed step to be obvious.
With respect to claims 39 and 40, Leufkens teaches continuous administration for 4-6 hours. See paragraph [0012]. Leufkens also suggests “single unit dosage forms,” ranging from 1-13 mg; these “single unit dosage forms” are considered to be equivalent to the claimed “loading dose.” See paragraph [0092].
With respect to claim 41, Leufkens provides for various embomdiments that would inform the ordinary artisan. In particular, Leufkens indicates that the 2-iminobiotin can be administered at 18 mg/day, using three doses per day, provided continuously for up to 10 hours per infusion. See paragraph [0012]. If it is assumed that there are three infusions per day, there would be 6 mg per infusion; if it is assumed that an infusion is 6 hours, that would be 1 mg/hour.
With respect to claim 42, Leufkins suggests adjusting the levels of 2-iminobiotin based upon eGFR levels. See paragraph [0014].
With respect to claims 43-48, all of these claims are drawn to how the treatment would affect the subject; these behaviors are outside of the control of the artisan, and would be inherent to the method. See MPEP 2112. Since both 2-iminobiotin and alteplase are both used for stroke treatment, there would be a reasonable expectation that both of these medications, individually, would provide for these effects. Therefore, there would be a reasonable expectation that the combination would also achieve these effects.
With respect to claim 49, Leufkins teaches 10 mg/kg/day. See paragraph [0048].
With respect to claim 50, Leufkins teaches 100-2000 ng*h/mL. See paragraph [0015].
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 30-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-11 and 13-18 of U.S. Patent No. 10,525,039 in view of Demaerschalk, et al (Stroke, 47, 581-641, 2016). The patent is drawn to a method of treating brain cell injury by administering 2-iminobiotin (see column 1, lines 18-25), wherein “brain cell injury” explicitly includes acute ischemic stroke. See column 8, line 28 The patent does not teach or suggest further including a fibrinolytic drug, like alteplase. As discussed in the rejections above, Demaerschalk teaches that alteplase is a standard of care for acute ischemic stroke/ Based upon this, in a clinical setting, it would be obvious to the ordinary artisan to combine two drugs known for treating acute ischemic stroke, wherein there is an expectation that the combined treatment would provide for a predictable enhancement in treatment over each drug individually.
The instant application provides for a method of treating acute ischemic stroke with a combination of 2-iminobiotin and a fibrinolytic drug. The patent provides for a broader disease-set, wherein the only other difference would be obvious to the ordinary artisan. As such, the instant application is considered an obvious variant of an already patented method.
Claims 30-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,426,387 in view of Demaerschalk, et al (Stroke, 47, 581-641, 2016). The patent is drawn to a method of treating brain hypoxic injury by administering 2-iminobiotin (see column 1, lines 18-25 and claim 1), wherein “brain hypoxic injury” explicitly includes acute ischemic stroke. See column 8, line 28 The patent does not teach or suggest further including a fibrinolytic drug, like alteplase. As discussed in the rejections above, Demaerschalk teaches that alteplase is a standard of care for acute ischemic stroke/ Based upon this, in a clinical setting, it would be obvious to the ordinary artisan to combine two drugs known for treating acute ischemic stroke, wherein there is an expectation that the combined treatment would provide for a predictable enhancement in treatment over each drug individually.
The instant application provides for a method of treating acute ischemic stroke with a combination of 2-iminobiotin and a fibrinolytic drug. The patent provides for a broader disease-set, wherein the only other difference would be obvious to the ordinary artisan. As such, the instant application is considered an obvious variant of an already patented method.
Conclusion
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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651