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 .
Election/Restrictions
Applicant’s election without traverse of methemoglobin as the species in the reply filed on 10/16/25 is acknowledged.
Applicant did not identify the claims readable on the elected species, see 9/18/25 Restriction Requirement, page 4. However, for compact prosecution all claims are examined.
Claim Status
Claims 1, 3, 4, and 7-11 are pending.
Claims 2, 5, 6 are cancelled.
Claims 1, 3, 4, and 7-11 are rejected.
Priority
The instant application, filed 02/24/2023 is a National Stage entry of PCT/JP2021/031458 , International Filing Date: 08/27/2021
claims foreign priority to 2020-144044, filed 08/28/2020.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 7/6/26 Information Disclosure Statement, and provides a signed and dated copy of such herewith.
Drawings
Response to Arguments
Applicant’s arguments, see page 6, filed 5/11/26, and replacement drawings, with respect to the drawings objection have been fully considered and are persuasive. The drawings objection has been withdrawn.
Specification
Response to Arguments
Applicant’s arguments, see page 6, filed 5/11/26, and amended title, with respect to the specification objection have been fully considered and are persuasive. The specification objection has been withdrawn.
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 11 recites the limitation "”the capsule" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Perhaps applicant meant for claim 11 to depend from claim 10.
Claim Rejections - 35 USC § 112
Response to Arguments
Applicant’s arguments, see pages 6-9, filed 5/11/26, and amended title, with respect to the 35 USC 112 scope of enablement rejection of claims 1-6 have been fully considered and are persuasive. The 35 USC 112 scope of enablement rejection of claims 1-6 has been withdrawn.
Applicant’s arguments, see page 9, filed 5/11/26, and amended title, with respect to the 35 USC 112 written description requirement rejection of claims 1 and 3-6 have been fully considered and are persuasive. The 35 USC 112 written description requirement rejection of claims 1 and 3-6 has been withdrawn.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments filed 5/11/26 have been fully considered but they are not persuasive as to the Rose rejection, below. As to previous rejections applying Smith and Gosselin or Ten eyck et al., these are withdrawn based on amendments applicant has made that render these no longer applicable by themselves under this section.
On pages 11-12 applicant argues against Rose for the 35 USC 102 rejection, and the following responds to this.
Rose uses the term “oxygen carriers” to denote “Molecules or compounds that are capable of binding, transporting and releasing oxygen in the body. Oxygen carriers include natural proteins, such as hemoglobin, myoglobin and hemocyanin, as well as artificial oxygen carriers, including hemoglobin-based oxygen carriers (HBOCs), perfluorocarbons (PFCs), liposome-encapsulated hemoglobin and porphyrin metal complexes,” para 64, emphases added. As well established and articulated in applicant’s arguments, the oxygen carrier hemoglobin, when oxidized to methemoglobin, THEN “does not have oxygen-binding capacity”, however the molecule itself, such as when reduced (ferrous form) is capable of binding, transporting and releasing oxygen to the body. “Oxygen carrier” is a term applied to a group of molecules capable of binding, transporting and releasing oxygen to the body; this does NOT mean that because of this nomenclature that somehow, when hemoglobin, and oxygen carrier, is oxidized to methemoglobin it “cannot be considered a “natural or artificial oxygen carrier in its oxidized state.”” It is an oxygen carrier because it is capable of such, however in the oxidized state, as well understood in the art, it loses that capacity. Rose claim 34 supports this abundantly, as do paras 103-104. Applicant’s arguments conflate a capability with a varying state of such oxygen carriers where in the oxidized state they do not have that capability (but the capability still exists, such as if the molecule of the oxygen carrier is reduced to its reduced state that provides for carrying oxygen).
Claim(s) 1, 3 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20190290739, published 9/26/19, inventors Rose et al. (“Rose”).
Claim 1 as interpreted under this rejection includes a method for treating a poisoning selected from the group consisting of cyanide poisoning, hydrogen sulfide poisoning and azide poisoning, the method comprising administering a medicament or pharmaceutical composition to a subject in need thereof comprising as an active ingredient(s) a vesicle containing methemoglobin.
Claim 3 depends from claim 1, wherein the vesicle containing the methemoglobin is a methemoglobin-containing erythrocyte or a methemoglobin-containing capsule.
Claim 4 depends from claim 3 and as reasonably interpreted further narrows the claim 3 to “the capsule comprises at least one selected from the group consisting of a liposome, a polymersome, and a polymer thin film.
Rose teaches and claims treating cyanide poisoning, claim 34 stating, “A method of treating cyanide poisoning in a subject, comprising: selecting a subject with cyanide poisoning; and administering to the subject a therapeutically effective amount of a composition comprising a natural or an artificial oxygen carrier, wherein the oxygen carrier is in its oxidized form,” claim 37 stating, “The method of claim 34, wherein the oxygen carrier is a natural oxygen carrier comprising a globin protein,” claim 38 stating, “The method of claim 37, wherein the globin protein comprises hemoglobin or myoglobin,” and paragraph 60 stating, “Methemoglobin: The oxidized form of hemoglobin in which the iron in the heme component has been oxidized from the ferrous (+2) to the ferric (+3) state. This renders the hemoglobin molecule incapable of effectively transporting and releasing oxygen to the tissues. Normally, there is about 1% of total hemoglobin in the methemoglobin form.” Similar to claim 34, paragraph 10 states, “Also provided is a method of treating cyanide poisoning in a subject by selecting a subject with cyanide poisoning and administering to the subject a therapeutically effective amount of a composition that includes a natural or an artificial oxygen carrier, wherein the oxygen carrier is in its oxidized form.” See also paragraphs 103-104. Rose also teaches in its section for treating cyanide poisoning, using a liposome-encapsulated globin protein, such as a liposome-encapsulated hemoglobin or a liposome-encapsulated myoglobin, paragraph 118. A liposome-encapsulated hemoglobin, where the hemoglobin is oxidized, this clearly set forth per above so that such liposome-encapsulated hemoglobin is methemoglobin, meets the newly added claim 1 requirement of “a vesicle containing methemoglobin”, this clearly at once envisaged when considering the relevant teachings of Rose. Rose also teaches in its section for treating cyanide poisoning, using a liposome-encapsulated globin protein, such as a liposome-encapsulated hemoglobin or a liposome-encapsulated myoglobin, paragraph 118, so that this is at once envisaged, and meets the newly added vesicle limitation of claim 1, which vesicle per claim 4, via claim 3, includes a capsule that comprises a liposome.
Claims 1, 3 and 4 accordingly are anticipated by Rose.
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.
Response to Arguments
Applicant's arguments filed 5/11/26 have been fully considered but they are not persuasive.
On pages 11-12 applicant argues against Rose for the 35 USC 102 rejection, and on page 12 refers back to this. The following is responsive to all arguments against Rose therein these sections.
Rose uses the term “oxygen carriers” to denote “Molecules or compounds that are capable of binding, transporting and releasing oxygen in the body. Oxygen carriers include natural proteins, such as hemoglobin, myoglobin and hemocyanin, as well as artificial oxygen carriers, including hemoglobin-based oxygen carriers (HBOCs), perfluorocarbons (PFCs), liposome-encapsulated hemoglobin and porphyrin metal complexes,” para 64, emphases added. As well established and articulated in applicant’s arguments, the oxygen carrier hemoglobin, when oxidized to methemoglobin, THEN “does not have oxygen-binding capacity”, however the molecule itself, such as when reduced (ferrous form) is capable of binding, transporting and releasing oxygen to the body. “Oxygen carrier” is a term applied to a group of molecules capable of binding, transporting and releasing oxygen to the body; this does NOT mean that because of this nomenclature that somehow, when hemoglobin, and oxygen carrier, is oxidized to methemoglobin it “cannot be considered a “natural or artificial oxygen carrier in its oxidized state.”” It is an oxygen carrier because it is capable of such, however in the oxidized state, as well understood in the art, it loses that capacity. Rose claim 34 supports this abundantly, as do paras 103-104. Applicant’s arguments conflate a capability with a varying state of such oxygen carriers where in the oxidized state they do not have that capability (but the capability still exists, such as if the molecule of the oxygen carrier is reduced to its reduced state that provides for carrying oxygen).
Claim(s) 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over US 20190290739, published 9/26/19, inventors Rose et al. (“Rose”), as applied to the rejection of claim 1 above, and further in view of Smith and Gosselin, Toxicology and Applied Pharmacology, 8, 159-172 (1966), provided in 1/6/25 IDS (“SG”).
Claim 1 is rejected as anticipated by Rose as set forth above.
New claim 7 depends from claim 1 and states that the composition is administered to the subject within 10 minutes after exposure to the cyanide, hydrogen sulfide or azide, and new claim 8 states that the composition is administered to the subject within 5 minutes after exposure to the cyanide, hydrogen sulfide or azide. This is for treating.
New claim 9 is directed to a method for preventing cyanide poisoning, hydrogen sulfide poisoning, and azide poisoning, the method comprising:
administering a medicament or a pharmaceutical composition for cyanide poisoning, hydrogen sulfide poisoning, and azide poisoning, the medicament or pharmaceutical composition comprising, as an active ingredient(s), a vesicle containing methemoglobin,
wherein the medicament or pharmaceutical composition is administered to a subject within 5 minutes prior to exposure to cyanide, hydrogen sulfide, or azide.
New claim 10 is directed to the method according to claim 9, wherein the vesicle containing methemoglobin is a methemoglobin-containing erythrocyte or a methemoglobin-containing capsule.
New claim 11 is directed to the method according to claim 9, wherein the capsule comprises at least one selected from the group consisting of a liposome, a polymersome, and a polymer thin film. This is interpreted to depend from claim 10 for this rejection.
Rose teaches and claims treating cyanide poisoning, claim 34 stating, “A method of treating cyanide poisoning in a subject, comprising: selecting a subject with cyanide poisoning; and administering to the subject a therapeutically effective amount of a composition comprising a natural or an artificial oxygen carrier, wherein the oxygen carrier is in its oxidized form,” claim 37 stating, “The method of claim 34, wherein the oxygen carrier is a natural oxygen carrier comprising a globin protein,” claim 38 stating, “The method of claim 37, wherein the globin protein comprises hemoglobin or myoglobin,” and paragraph 60 stating, “Methemoglobin: The oxidized form of hemoglobin in which the iron in the heme component has been oxidized from the ferrous (+2) to the ferric (+3) state. This renders the hemoglobin molecule incapable of effectively transporting and releasing oxygen to the tissues. Normally, there is about 1% of total hemoglobin in the methemoglobin form.” Similar to claim 34, paragraph 10 states, “Also provided is a method of treating cyanide poisoning in a subject by selecting a subject with cyanide poisoning and administering to the subject a therapeutically effective amount of a composition that includes a natural or an artificial oxygen carrier, wherein the oxygen carrier is in its oxidized form.” See also paragraphs 103-104.
Based on the above, a person of ordinary skill in the art would understand that methemoglobin is among the claim 37 hemoglobins administered in claim 34, the latter requiring that the oxygen carrier is in its oxidized form.
Although Rose clearly teaches the method of claim 1 for treating cyanide poisoning, Rose does not explicitly teach the timing limitations of claims 7 and 8 for treating, nor preventing cyanide poisoning, nor treating or preventing hydrogen sulfide poisoning nor azide poisoning as set forth in new claims 9-11.
The level of ordinary skill in the art is high.
As to new claims 7 and 8, SG on page 159 teaches “All deaths from sulfide and cyanide in these studies occurred within 5 minutes of the anion challenge, although the animals were observed for 24 hours,” so clearly suggesting the very high importance of administering a therapeutic/treating dose of methemoglobin (this the primary therapeutic of SG, see Title, page 159, and experiments) within this short time period after a poisoning event. Accordingly, one of ordinary skill in the art would have recognized this need to administer a therapeutic dose of methemoglobin, whether as is or in a vesicle such as a liposome as taught by Rose, within 5 minutes after a poisoning event, in an effort to reduce the effects of such poisoning. There would have been a reasonable expectation of success given the results of SG. As such claims 7 and 8 would have been obvious and are rejected under this section.
As to new claims 9-11, SG clearly teaches that methemoglobin is recognized to protect, as demonstrated in mice, against the lethality of subsequent challenge by sodium azide and sodium or hydrogen sulfide, and that “methemoglobin is presently recognized to afford protection against three toxic anions in vivo, namely cyanide, sulfide and azide,” Abstract on page 159. See also the experiments demonstrating effectiveness, including Tables 1 and 2, Fig. 3, Table 5 and associated text. On page 160 SG states, “In all cases heme pigments were assayed by the Drabkin reagent (Hawk et al.,1954) and were administered to mice by the intraperitoneal route. This treatment was followed in 2 minutes by an intraperitoneal injection of 0.3-0.9 ml of a sodium sulfide solution.” As to claim 9’s “within 5 minutes prior to exposure to cyanide, hydrogen sulfide, or azide,” the timing before such exposures is consistent with SG’s preventative administering of its heme pigments, these focusing on methemoglobin, which per page 160 was followed in 2 minutes by an intraperitoneal injection of a toxin, this being a sodium sulfide solution (sodium sulfide being a toxic agent similar to and representative of the claimed hydrogen sulfide, please note that SG’s administered sulfide caused squirming by the test rodents, see page 160). Considering this and other teachings of SG as to timing that include “before” but not specific time limit, one of ordinary skill in the art would recognize that protection is achieved by administering methemoglobin before (per Table 2’s description on page 162) administering the toxin, and also considering the “followed in 2 minutes” statement, claim 9’s “within 5 minutes prior to exposure to cyanide, hydrogen sulfide, or azide,” would have been obvious and specifically encompasses SG’s stated 2 minute timing. Additionally, on page 167 reference is made to “the short duration of these experiments,” further supporting a short period of time between administering a preventative dose prior to an administration of a toxic dose of interest.
Based on the teachings and examples in SG, when considering the treatment approaches in Rose for treating cyanide poisoning, one of ordinary skill in the art would have reasonably concluded that the same treatment approaches taught in Rose, including using liposomes (this meeting claim 9’s vesicle, claim 10’s methemoglobin-containing capsule, and claim 11’s liposome as the capsule type), would have been effective to treat hydrogen sulfide poisoning and azide poisoning, and also, based on SG, at least under particular and specific conditions, to prevent all of cyanide poisoning, hydrogen sulfide poisoning and azide poisoning, and to be administered for preventative purposes before the poisoning, within five minutes before such poisoning per above.
The rationale is applying a known technique to a known method ready for improvement or expansion to yield predictable results. Rose taught a "base" method for treating cyanide poisoning upon which the claimed invention can be seen as an "improvement”, expanding the scope of practice to include preventing cyanide poisoning and also treating and preventing hydrogen sulfide poisoning and azide poisoning. SG teaches known techniques and knowledge, regarding methemoglobin recognized to afford protection against cyanide, sulfide and azide toxic anions, that is applicable to the Rose method to expand its usage. Given the teachings and examples of Rose and SG, one of ordinary skill in the art would have recognized that applying the known technique and knowledge of SG would have yielded predictable results and resulted in improved and expanded methods to expand Rose’s methods to also prevent, under particular and specific conditions, cyanide poisoning, and also to treat hydrogen sulfide poisoning and azide poisoning, and to prevent these under particular and specific conditions. There would have been a reasonable expectation of success given the strong teachings of SG.
Accordingly, claims 7-11 would have been obvious.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JOSEPH FISCHER whose telephone number is (571)270-7925, and whose direct facsimile number is (571)270-8925. The examiner can normally be reached on Monday to Friday, 9:00 AM to 5:00 PM, however noting that the examiner will not normally be working on Monday/Tuesday and on Wednesday-Friday on alternating weeks, but will promptly answer messages upon his return to work.
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/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
