DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Status of Claims
The amendment, filed on 29 January 2026, is acknowledged.
Claims 9-11 and 19-20 have been amended.
Claims 7-8, 13, and 18 were previously withdrawn from consideration as being drawn to a nonelected species in the non-final Office Action mailed on 29 July 2025.
Claims 1-6, 9-12, 14-17, and 19-20 are pending and under consideration in the instant Office Action, to the extent of the following previously elected species:
the ocular disease treated is retinopathy;
there are no biomolecules present in the method;
there is no alcohol present in the method; and
the route of administration is oral.
Objections Withdrawn
Objections to Claims
Applicant’s amendments to claims 10-11 and 19-20, submitted on 29 January 2026, have overcome the objections to the claims set forth in the Office Action mailed on 29 July 2025. Accordingly, the relevant objections are withdrawn.
Rejections Withdrawn
Rejections pursuant to 35 U.S.C. § 112
The rejections of claims 9, 11, and 19 under 35 U.S.C. § 112 are withdrawn in view of Applicant’s amendments to the claims.
Maintained Rejections
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.
Claims 1-6, 9-12, 14-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Gomperts et al. (U.S. Patent No. 10,716,806 B2, published on 21 July 2020, provided by Applicant in IDS, hereafter referred to as Gomperts) and Biermann et al. (IOVS, 2010, 51 (7), 3784., provided by Applicant in IDS, hereafter referred to as Biermann).
Gomperts teaches a method for delivering carbon monoxide (CO) to subjects suffering from diseases comprising administration of a liquid composition in which CO is dissolved in a therapeutic amount (Abstract). The disease to be treated is one that “is treatable with carbon monoxide” such as sickle cell disease, inflammatory bowel disease, cardiovascular diseases, and others (claim 1 and column 1, line 66 - column 2, line 27). Gomperts teaches the CO to be dissolved or entrapped in a liquid, which may be water, ethanol, or both, and may optionally comprise biomolecules, flavorings, or vitamins (claims 11-12 and column 8, line 60 - column 9, line 37). The preferred concentration of CO in the liquid composition is taught to be 100-400 mg/L (claims 1-2 and column 7, lines 48-55). In one embodiment, the route of administration is taught to be oral ingestion (claim 6). Finally, Gomperts teaches the method of administering the CO-containing liquid in an amount to achieve a carbonmonoxy-hemoglobin (CO-Hb) concentration “suitable for the disease or disorder being treated”, preferably between 3-15% (column 12, lines 35-47). This can be achieved via dosing regimens that include multiple equally spaced doses per day or a single dose per day for one day, or daily administration indefinitely because “there is no known detrimental effect to long-term exposure to CO at these levels” (column 12, lines 49-65).
Guidelines on the obviousness of similar and overlapping ranges, amounts, and proportions are provided in MPEP § 2144.05. With respect to claimed ranges which “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). These guidelines apply to the concentration of CO in the liquid composition and the induced CO-Hb concentrations in the blood of the patient. In both cases, the ranges taught by Gomperts either fall within or significantly overlap the ranges recited in instant claims 9-10, which are therefore prima facie obvious.
Gomperts does not teach their method to treat retinopathy nor the treated subject to have diabetes. These deficiencies are offset by the teachings of Biermann.
Biermann teaches the impact of retinal ischemia/reperfusion (I/R) injury on retinal neurons and the role CO may have in mitigating damage or protecting from I/R injury (Abstract, Purpose). I/R injury is taught to play a significant role in the pathophysiology of many ocular diseases, including diabetic retinopathy (pg. 3784, left column, para. 1). One method of mitigating damage or protecting from ischemia is ischemic preconditioning (IPC), a therapy for tissues with high sensitivity against ischemia, which involves external stimuli which mobilize intrinsic protective mechanisms in the tissue, subsequently increasing tolerance against subsequent ischemia (pg. 3784, right column, para. 1). An example of a chemical which can provide IPC is carbon monoxide, which has been observed to exert anti-inflammatory and cytoprotective properties and reduce apoptosis in neuronal and non-neuronal tissues (pg. 3784, right column, para. 1-2). Specifically, CO has been observed to reduce oxidative or ischemic damage to retinal cells in the eye (pg. 3784, right column, para. 2). Biermann concludes that IPC with CO “mediates anti-inflammatory and antiapoptotic effects in retinal I/R injury, thus making it neuroprotective” (Abstract, Conclusions).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the invention of Gomperts with the teachings of Biermann to arrive at the claimed invention because applying a known technique to a disease that is known to benefit from the active pharmaceutical ingredient therein produces predictable results. Gomperts teaches a method with water and CO at a concentration that overlaps with the range recited in the instant application, and an oral route of administration, but does not teach retinopathy nor subjects with diabetes to be treated by the method. Biermann teaches that I/R injury plays a significant role in the pathophysiology of diabetic retinopathy, among other diseases, and that CO can mitigate damage or protect from I/R injury. An ordinary artisan would be motivated to apply the method taught by Gomperts to a patient with diabetes to treat retinopathy in view of the teachings of Biermann because an increased breadth of potential patients is desirable for a therapeutic method and Biermann teaches that the method will have positive effects. As a result, there is a reasonable expectation of success in arriving at the method of instant claims 1-6, 9-12, 14-17, and 19-20 in view of the teachings of Gomperts and Biermann.
Response to Arguments
The Applicant’s arguments, filed on 29 January 2026, have been fully considered but are not persuasive.
In para. 2 of pg. 7 of the remarks, Applicant argues that the oral formulations taught by the Gomperts reference would not be expected to apply to ocular diseases “simply because Biermann shows inhaled CO formulations have some success”. This is interpreted as an argument against the combination of the references. In response, the Examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the Biermann reference was not used for its teachings regarding route of administration; rather, the reference was used for its teaching that CO can be useful for treating ocular disease, including in diabetic subjects. The Gomperts reference teaches oral administration of a composition comprising CO as a method of treatment and it would have been reasonable for a person of ordinary skill in the art to try using the composition of Gomperts to treat subjects experiencing ocular disease because, as stated above, it would provide a wider breadth of potential patients for the invention of Gomperts, which an ordinary artisan would recognize as desirable, and Biermann teaches that administration of CO to these subjects will have positive effects. As a result, Applicant’s argument is not found to be persuasive.
From the final para. of pg. 7 to the penultimate para. of pg. 10, Applicant discussed the difficulties in treating ocular disease. This is acknowledged, but does not address the obviousness of the claimed method in view of the combination of references above and is therefore not a persuasive argument against the rejection of the claimed method.
In the para. spanning the bottom of pg. 10 and top of pg. 11, Applicant states that following the method of Biermann would produce significantly greater concentrations of carboxyhemoglobin (COHb) than those in the experiments disclosed in the instant application. The Biermann reference was not used for its teachings regarding concentrations of CO and the argument is therefore considered moot.
In para. 2 of pg. 11, Applicant argues that, in view of the Gaudana, Scott, and Wang references, in combination with data disclosed in the instant application, “one of skill in the art would not be motivated to move to an oral route of administration”. This argument is directed to references supplied by the Applicant in the remarks filed on 29 January 2026, and not to the argument and motivation presented in the rejection under 35 U.S.C. § 103 above, therefore it is not found to be persuasive.
Finally, from the final para. of pg. 11 to para. 1 of pg. 13, Applicant argues that they have found oral administration of CO to be unexpectedly good for treating ocular diseases, that the results “had to be determined empirically, and could not have been reasonably predicted based on any results using inhalation as the method of administration”, and that the “level of success is also therefore unexpected”.
Guidelines on determining whether results are expected or unexpected are provided in MPEP § 716.02. To demonstrate that results are unexpected and significant, the Applicant has the responsibility of presenting evidence that establishes “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance” (bold added for emphasis). Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). “Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims” (bold added for emphasis). See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e).
The results discussed from the final para. of pg. 11 to para. 1 of pg. 13 are not considered to be unexpected and unobvious because the Biermann reference teaches that administration of CO is effective in the treatment of diabetic patients experiencing ocular disease. In addition, the Gomperts reference teaches an oral route of administration of a composition comprising CO in concentrations that overlap with the ranges recited in the instant application. Administering the composition rendered obvious by the teachings of the Gomperts reference to treat ocular disease in diabetic patients is prima facie obvious in view of the teachings of Gomperts and Biermann.
The Applicant also has not demonstrated unexpected results commensurate in scope with the claimed invention. “To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range.” In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). See MPEP § 716.02(d). Only one example outside the claimed range has been provided in the form of a vehicle which contains no added CO (instant spec. pg. 35, lines 9-10). The concentration of CO in Examples 2-7 is only stated as 2 mg/kg or 10 mL/kg 5x/week (HBI-002 treatment), which encompasses one value inside the claimed range of 100-4,400 mg/L or 100-800 mg/L (instant claims 10 and 20) and therefore does not demonstrate the criticality of the claimed range.
The Applicant also has not compared their invention with the closest prior art. See MPEP § 716.02(e). The comparison provided in the instant specification is with an absence of added CO (presented as a treatment with the vehicle). Gomperts, which was provided by Applicant in the IDS filed on 30 January 2024, and used in a rejection under 35 U.S.C. § 103 in the previous Office Action, teach compositions that comprise CO in concentrations that overlap with the ranges recited in the instant application, such as 100-400 mg/L (Gomperts, claims 1-2 and column 7, lines 48-55). Therefore, a comparison with the closest subject matter in the prior art should include a comparison to Gomperts.
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 1-6, 10, 12, and 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, and 12 of U.S. Patent No. 10,716,806 B2, in view of Biermann (IOVS, 2010, 51 (7), 3784., provided by Applicant in IDS).
U.S. Patent No. 10,716,806 B2 recites a method for delivering carbon monoxide (CO) to subjects suffering from diseases that are “treatable with carbon monoxide” comprising administration of a liquid composition in which CO is dissolved in a therapeutic amount, specifically 85-400 mg/L (claims 1-2). Patent ‘806 recites the CO to be dissolved or entrapped in a liquid, which may be water, ethanol, or both (claim 12). The route of administration is recited as oral ingestion (claim 6).
U.S. Patent No. 10,716,806 B2 does not recite their method to treat retinopathy nor the treated subject to have diabetes. These deficiencies are offset by the teachings of Biermann.
Biermann teaches the impact of retinal ischemia/reperfusion (I/R) injury on retinal neurons and the role CO may have in mitigating damage or protecting from I/R injury (Abstract, Purpose). I/R injury is taught to play a significant role in the pathophysiology of many ocular diseases, including diabetic retinopathy (pg. 3784, left column, para. 1). One method of mitigating damage or protecting from ischemia is ischemic preconditioning (IPC), a therapy for tissues with high sensitivity against ischemia, which involves external stimuli which mobilize intrinsic protective mechanisms in the tissue, subsequently increasing tolerance against subsequent ischemia (pg. 3784, right column, para. 1). An example of a chemical which can provide IPC is carbon monoxide, which has been observed to exert anti-inflammatory and cytoprotective properties and reduce apoptosis in neuronal and non-neuronal tissues (pg. 3784, right column, para. 1-2). Specifically, CO has been observed to reduce oxidative or ischemic damage to retinal cells in the eye (pg. 3784, right column, para. 2). Biermann concludes that IPC with CO “mediates anti-inflammatory and antiapoptotic effects in retinal I/R injury, thus making it neuroprotective” (Abstract, Conclusions).
It would have been prima facie obvious to a person of ordinary skill in the art, prior to the filing of the instant application, to modify the method of Patent ‘806 with the teachings of Biermann to arrive at the method of instant claims 1-6, 10, 12, and 14-17 because applying a known technique to a disease that is known to benefit from the active pharmaceutical ingredient therein produces predictable results. Patent ‘806 recites a method with water and CO and an oral route of administration, the same as the method recited in the instant application, but does not teach retinopathy nor subjects with diabetes to be treated by the method. Biermann teaches that I/R injury plays a significant role in the pathophysiology of diabetic retinopathy, among other diseases, and that CO can mitigate damage or protect from I/R injury. An ordinary artisan would be motivated to apply the method recited by Patent ‘806 to a patient with diabetes to treat retinopathy in view of the teachings of Biermann because an increased breadth of potential patients is desirable for a therapeutic method and the Biermann reference teaches that the method will have positive effects. As a result, there is a reasonable expectation of success in arriving at the method of instant claims 1-6, 10, 12, and 14-17 in view of the method recited by U.S. Patent No. 10,716,806 B2 and the teachings of Biermann.
Claims 1-6, 10, 12, and 14-17 are directed to an invention not patentably distinct from claim 1-2, 6, and 11-12 of commonly assigned U.S. Patent No. 10,716,806 B2, in view of Biermann. Specifically, see above.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned U.S. Patent No. 10,716,806 B2, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
Response to Arguments
A complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by the Applicant showing that the claims subject to the restriction are patentably distinct from the reference claims, or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional.
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 Sean J. Steinke, Ph.D., whose telephone number is (571) 272-3396. The examiner can normally be reached Mon. - Fri., 09:00 - 17:00 ET.
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/S.J.S./
Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619