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 . 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.
Priority
The instant application claims domestic benefit to US provisional application no. 63/273,317 filed on 10/29/2021.
Status of the Claims
The claim amendments and remarks filed on 01/20/2026 is acknowledged. Claims 1, 6-8, and 10 are amended. Claims 1-20 are pending.
Claims 11-20 were previously withdrawn in the office action dated 12/26/2024 from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Accordingly, claims 1-10 are being examined on the merits herein.
Withdrawn Rejections
The 35 USC 102 rejection over Reznick for claim 6 is withdrawn because claim 6 was rejected for previously reciting an intended use that did not limit the structure of the composition. However, claim 6 now recites “amount of the cyanide antidote is greater than that of the metal ion chelator”, which is a new limitation that requires new search and consideration.
The 35 USC 103 rejection over Reznick for claim 6 is withdrawn because claim 6 was rejected for previously reciting an intended use that did not limit the structure of the composition. However, claim 6 now recites “amount of the cyanide antidote is greater than that of the metal ion chelator”, which is a new limitation that requires new search and consideration.
The 35 USC 103 rejection over Reznick in view of Choi and Forsyth for claim 8 is withdrawn because the rejection here relied on preparing the hydroxocobalamin of Reznick at 5% weight of the composition as suggested by Forsyth et al. and the iron chelators of Reznick and Choi. at 5% weight of the composition. However, claim 8 now depends on claim 6, which recites “amount of the cyanide antidote is greater than that of the metal ion chelator”.
The following grounds of rejection are maintained, amended, and new as necessitated by Applicant’s amendments.
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.
Claim 8 is 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 8 recites “… comprises 5 to 10 parts by weight of the cyanide antidote, and 1 to 5 parts by weight of the metal ion chelator.”, which encompasses an embodiment in which there is 5 parts by weight of the cyanide antidote and 5 parts by weight of the metal ion chelator.
Claim 6 (claim 8 depends from claim 6) recites “amount of the cyanide antidote is greater than that of the metal ion chelator”. Therefore, claim 8 fails to include all the limitations of the claim upon which it depends on if the composition of claim 8 comprises 5 parts by weight cyanide antidote and 5 parts by weight of the metal ion chelator.
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 § 102
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.
Claim(s) 1-2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Reznick et al. (US20030031630A1 in PTO-892 dated 12/26/2024).
Reznick et al. discloses a method of reducing tobacco smoke-associated injury or diseases in the aerodigestive tract of a subject, comprising administering a therapeutically effective amount of an antioxidant agent (see Abstract). Reznick recites “More particularly, the present invention relates to methods of employing hydroxocobalamin (vitamin B12a, OH—CO), deferoxamine (DES) and reduced glutathione (GSH) to reduce or prevent tobacco smoke (TS)-induced cellular or macromolecular damage in the aerodigestive tract.” (see paragraph 0001). Reznick et al. discloses their compositions can be administered by a route selected from the group consisting of the intranasal, transdermal, intradermal, oral, buccal, parenteral, topical, rectal and inhalation route (see paragraph 0040). Reznick et al. discloses pharmaceutical compositions for parenteral administration including aqueous solutions of the active preparation in water-soluble form (see paragraph 0151). Reznick et al. discloses the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use (see paragraph 0152).
Therefore, claims 1-2 and 5 are anticipated.
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.
Claim(s) 1-2 and 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Reznick et al. (US20030031630A1 in PTO-892 dated 12/26/2024).
Reznick et al. discloses a method of reducing tobacco smoke-associated injury or diseases in the aerodigestive tract of a subject, comprising administering a therapeutically effective amount of an antioxidant agent (see Abstract). Reznick recites “More particularly, the present invention relates to methods of employing hydroxocobalamin (vitamin B12a, OH—CO), deferoxamine (DES) and reduced glutathione (GSH) to reduce or prevent tobacco smoke (TS)-induced cellular or macromolecular damage in the aerodigestive tract.” (see paragraph 0001). Reznick et al. discloses their compositions can be administered by a route selected from the group consisting of the intranasal, transdermal, intradermal, oral, buccal, parenteral, topical, rectal and inhalation route (see paragraph 0040). Reznick et al. discloses pharmaceutical compositions for parenteral administration including aqueous solutions of the active preparation in water-soluble form (see paragraph 0151). Reznick et al. discloses the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile, pyrogen-free water, before use (see paragraph 0152).
Reznick et al. demonstrates in Example 1 that hydroxocobalamin provided protection from tobacco smoke-induced loss of aerodigestive tract antioxidant defenses (see paragraphs 0164-0202). Reznick et al. discloses that various tobacco smoke contain cyanide, and further demonstrates in Example 1 that the addition of cyanide (KCN) caused ~65% loss of OPO activity after only 2 minutes of incubation (see paragraph 0199). Reznick et al. shows that hydroxocobalamin acts as a chelator of cyanide and prevents the loss of OPO activity in saliva 40 mins after treatment with tobacco smoke (see paragraph 0201 and FIG. 14). Reznick et al. also demonstrates in Example 2 that the combination of deferoxamine and glutathione was effective for preventing upper aerodigestive tract lymphocyte death associated with exposure to tobacco smoke (see paragraph 0203-0228). Reznick et al. shows that this combination provided higher survival rates at 80 minutes tobacco smoke exposure than a control and glutathione administered alone (61.6% - 5 mM deferoxamine and 1 mM glutathione compared to 14.4% control and 28.8% 1mM glutathione alone in Table 2 of Reznick). Reznick discloses that the use of antioxidants, such as glutathione and redox-active metal chelators, such as deferoxamine, preferably in combination, represents a significant improvement over prior art methods of preventing or reducing TS-mediated oxidant injury in the aerodigestive tract (see paragraph 0123). Reznick et al. discloses in another embodiment, the administration of a combination including some or all of the following antioxidants; L-glutathione, … N-acetyl-l-cysteine, … in order to provide intra-oral protection from oxidant injury (see paragraph 0034).
To the extent that Applicant argues that instant claims 1-2 and 5 are not anticipated, as an alternative, it would have been prima facie obvious before the effective filing date of the claimed invention to combine the hydroxocobalamin and the deferoxamine / glutathione composition as disclosed in Reznick et al. to arrive at the claimed invention. One of ordinary skill in the art would have prepared this combination because Reznick et al. discloses that both compositions are useful for the same purpose of preventing or reducing tobacco smoking-related injuries. See In re Kerkhoven, MPEP 2144.06 section I. Furthermore, the recited limitation “for use in protection from fire injury caused by inhalation of toxic gas containing cyanide” is an intended use and does not limit the structure of the recited composition because the recited intended use is a mere statement of purpose of use. See MPEP 2111.02. Therefore, the combination of Reznick described above meets all of the structural limitations of the recited composition.
In regards to claim 4, it would also be prima facie obvious before the effective filing date of the claimed invention to have further combined the composition comprising N-acetyl-l-cysteine as disclosed by Reznick et al with the compositions of deferoxamine / glutathione and hydroxocobalamin of Reznick et al. to arrive at the claimed invention. One of ordinary skill in the art would have made prepared this combination because Reznick et al. discloses that these compositions are all useful for the same purposes of preventing or reducing tobacco smoke-related injuries as well as the administration of combinations of antioxidant agents. See In re Kerkhoven, MPEP 2144.06 section I.
Claim(s) 3, 7, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Reznick et al. (US20030031630A1 in PTO-892 dated 12/26/2024), as applied to claims 1-2 above, and further in view of Choi et al. (US20180360815A1 in PTO-892 dated 06/03/2025).
The teachings of Reznick et al. are as described above. Reznick et al. teaches the compositions recited in claims 1 and 2 as discussed above. Furthermore, Reznick et al. discloses compositions to reduce pathogenesis of oxidant stress associated diseases of the aerodigestive tract (see paragraph 0001), and further teaches examples of these diseases associated with tobacco smoke such as chronic obstructive pulmonary disease (COPD) (see paragraph 0160)
The difference between Reznick et al. and the claimed invention is that Reznick et al. does not disclose a composition further comprising deferiprone or deferasirox.
Choi et al. discloses a method for treating one or more symptoms of chronic obstructive pulmonary disease (COPD) comprising administering to a subject in need of treatment a therapeutically effective amount of one or more mitochondrial iron chelators such as deferiprone (see Abstract). Choi et al. discloses that the pathogenesis of COPD remains poorly understood, but involves aberrant inflammatory and dysregulated cellular responses of the lung to cigarette smoke (CS) exposure and that CS exposure remains the greatest environmental risk factor for COPD (see paragraph 0003). Choi et al. discloses that deferiprone is a neutral compound compared to deferoxamine, which is positively charged (see paragraph 0027). Therefore, Choi et al discloses that after binding iron, the deferiprone-iron complex becomes hydrophilic, meaning it can also chelate iron from the cytosol and other hydrophilic compartments. In contrast, deferoxamine is only suitable for the chelation of extracellular or plasma membrane bound iron, entering cells only by endocytosis and unable to cross inside intracellular organelles such as mitochondria (see paragraph 0027).
It would have been prima facie obvious before the effective filing date of the claimed invention to have further include in the combination of Reznick et al. as described above with the deferiprone of Choi et al. to arrive at the claimed invention. One of ordinary skill in the art would made this modification with a reasonable expectation of success because both Choi et al. and Reznick et al. teach that their respective compositions are useful for the same purpose of treating tobacco smoke-related diseases such as COPD, and Choi et al. provides further guidance that deferiprone can chelate iron from the cytosol and other hydrophilic compartments due its neutral state, whereas positively charged deferoxamine only enters cells by endocytosis and is unable to cross inside intracellular organelles such as mitochondria. Therefore, an ordinary skilled artisan would have been motivated to further include deferiprone as disclosed in Choi et al. in order to provide these additional benefits.
Claim(s) 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Reznick et al. (US20030031630A1 in PTO-892 dated 12/26/2024), as applied to claim 1 above, and further in view of Forsyth et al. (Clinical Toxicology, 1993 in PTO-892 dated 06/03/2025) and Clements (WO2018232452A1 in PTO-892).
The teachings of Reznick are as described above and teach the composition of claim 1 as discussed above.
Reznick, however, does not disclose the amount of the cyanide antidote is greater than that of the metal ion chelator as well as a composition comprising 5-10 parts by weight cyanide antidote and 1 to 5 parts by weight metal ion chelator.
Forsyth et al. discloses the safety, efficacy, and pharmacokinetic parameters of 5 grams of hydroxocobalamin given intravenously, alone or in combination with 12.5 grams of sodium thiosulfate to healthy adult men who were heavy smokers (see Abstract). Forsyth et al. discloses that the hydroxocobalamin was administered at 5% by weight (5 g in 100 mL) via iv injection (see page 279 under “Medications and Administration”). Forsyth also discloses that oral dosing of 20-60 mg of hydroxocobalamin daily also reduce both blood and urinary cyanide levels for normal smoking subjects and smokers with tobacco amblyopia (see second to last paragraph on page 289). Forsyth et al. concludes that the administrated hydroxocobalamin was effective for rapidly decreasing whole blood cyanide levels in heavy smokers, and that the administered amount did not cause any significant side effects and may be safe and efficacious for the treatment of cyanide poisoned patients (see Conclusions on page 291-292).
Clements discloses a method of treating inflammation in the lung by administering a high concentration of an inhaled chelating agent (Abstract). Clements discloses that the inflammation can be caused by cigarette smoke and others (paragraph 00117 page 20). Clements discloses the chelating agent can be deferoxamine or deferasirox (paragraph 0048 page 8). Clements discloses that the amount of chelating agent dose can be between 37.5 to 1200 mg/day (paragraph 0087 page 14).
Clements demonstrates in Example 3 (page 26) that cigarette smoke-induced pulmonary inflammation can be treated by administering a high dose of chelator the lungs. Clements demonstrates in Figure 5 that cigarette-smoke significantly increased BALF leukocytes, which induced pulmonary inflammation, and that treatment with deferoxamine significantly reduced this effect (paragraphs 00151-11156).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the composition disclosed by Reznick described above by preparing the hydroxocobalamin of Reznick at 5 grams as disclosed by Forsyth et al. and deferoxamine of Reznick between 37.5 to 1200 mg as disclosed in Clements and perform routine optimization to arrive at the recited weights by parts. One of ordinary skill in the art could have performed routine optimization because Reznick teaches the use of hydroxocobalamin and deferoxamine in aqueous solutions for treating tobacco-smoke associated injury in a subject, Forysth discloses that 5 grams of hydroxocobalamin is effective for treating cigarette smoke exposed patients, and Clements discloses that 37.5 to 1200 mg is also an effective amount of deferoxamine to treat cigarette smoke exposed patients. Therefore, an ordinary skilled artisan could have, for example, prepared an aqueous composition of Reznick having 5 grams of hydroxocobalamin and 1 gram of deferoxamine, which would contain 5 parts by weight hydroxocobalamin and 1 part by weight deferoxamine. See MPEP 2144.05 II.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Reznick et al. (US20030031630A1 in PTO-892 dated 12/26/2024) in view of Choi et al. (US20180360815A1 in PTO-892 dated 06/03/2025), as applied to claims 7 and 9 above, and further in view of Forsyth et al. (Clinical Toxicology, 1993 in PTO-892 dated 06/03/2025) and Arnold et al. (WO2014070769A1 in PTO-892 dated 12/26/2024).
The combined teachings of Reznick and Choi are as described above and teach the composition recited in claims 7 and 9 as discussed above. Furthermore, Choi et al. discloses that their mitochondrial iron chelator (referred to as an active agent) can be in the form of a nanoparticles, and that the active agent can make up 5-90% by total weight of the nanoparticle (see paragraph 0042).
The combined references, however, do not disclose a composition comprising 5 to 10 parts by weight the cyanide antidote and 5-10 parts by weight the expectorant such as N-acetyl cysteine.
The teachings of Forsyth are described above.
Arnold et al. discloses compositions and formulations comprising glutathione with or without thiocyanate and methods of use thereof to treat diseases and disorders in mucosal/epithelial tissue (see Abstract). Arnold et al. discloses that in some embodiments, their composition can include precursors to glutathione such as N-acetyl cysteine, in amounts from about 0.1% to about 10% by weight, while maintaining the weight ratios of the other components (see page 3 lines 15-20). Arnold et al. discloses that their compositions can be used to establish and/or maintain homeostasis in the mucosal environment of the lungs of a smoker or former smoker to reduce the risk or incidence of lung cancer and/or smoking-related diseases or disorders (see page 94 lines 7-13). Arnold et al. discloses that precursors such as N-acetyl cysteine enable glutathione to be produced intracellularly. Arnold et al discloses that this can be important in certain embodiments, as glutathione is not taken up by cells, and will not work if supplied on the outside of the cell. Arnold et al. discloses that in some embodiments, a composition of this invention comprising a glutathione precursor in place of glutathione can be used to perfuse the vasculature of an organ and a composition of this invention comprising glutathione can be used to perfuse the airway of an organ, to preserve endothelial function. Thus, the compositions and formulations of this invention can be used to preserve both mucosal and endothelial tissue (see page 20 lines 7-18).
It would have been prima facie obvious before the effective filing date of the claimed invention to have modified the composition as suggested by the combined teachings of Reznick and Choi described above by preparing the hydroxocobalamin of Reznick at 5% weight of the composition as disclosed by Forsyth et al., the iron chelators of Reznick and Choi. at 5% weight of the composition as suggested by Choi, and preparing the N-acetyl cysteine of Reznick at 5-10% weight of the composition as suggested by Arnold et al. to arrive at the claimed invention. One of ordinary skill in the art would have made the modifications to the hydroxocobalamin and iron chelators with a reasonable expectation of success because Forsyth et al. provides guidance that 5% by weight hydroxocobalamin is suitable for treating patients who are heavy smokers with no significant side effects, and Choi et al. provides guidance that iron chelators at 5% weight of the composition are also suitable for treating smoke-related injuries. Therefore, an ordinary skilled artisan could have performed routine optimization to modify the parts by weight of the hydroxocobalamin and iron chelators and arrive at the optimal combinations. Furthermore, one of ordinary skill in the art would have made the modification to the n-acetyl cysteine with a reasonable expectation of success because Arnold et al. provides guidance that this weight range of N-acetyl cysteine is suitable for compositions to reduce the risk or incidence of lung cancer and/or smoking-related diseases or disorders with an added advantage of enabling glutathione to be produced intracellularly.
Response to Arguments
Applicant’s arguments filed on 01/20/2026 have been fully considered in so far as they apply to the rejections of the instant office action, but were not persuasive.
Applicant states that Reznick merely describes “methods of utilizing hydroxocobalamin, deferoxamine, and GSH”. Applicant states that in this context, these compounds should be understood a list of individual ingredients rather than a specific description of a composition. Applicant states that there are multiple combinations of two or three components and among these possibilities, combinations such as hydroxocobalamin + GSH or deferoxamine + GSH are not what is claimed in the present application. Applicant further cites to In re Arkley (455 F.2d 586) that a prior art only anticipates if it “clearly and unequivocally” discloses the claimed compound or directs a person skilled in the art to the specific combination “without any need for picking, choosing, and combining various disclosures”. Applicant states that the hydroxocobalamin and deferoxamine were selected from the various possibilities in Reznick and therefore violates the standards for anticipation under the aforementioned case law. Applicant further states that in the examples and claims of Reznick, hydroxocobalamin and deferoxamine are tested separately and claimed separately. Therefore, Applicant states that Reznick should be seen as disclosing these two compounds separately and not in a combination.
Applicant’s arguments described above were not found persuasive because MPEP 2131.02 III states that “A reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." and “Kennametal does not stand for the proposition that a reference missing a limitation can anticipate a claim if a skilled artisan viewing the reference would "at once envisage" the missing limitation. Rather, Kennametal addresses whether the disclosure of a limited number of combination possibilities discloses one of the possible combinations."
Here, while Reznick does not explicitly disclose a combination of hydroxocobalamin and deferoxamine, Reznick does explicitly state “methods of employing hydroxocobalamin (vitamin B12a, OH—CO), deferoxamine (DES) and reduced glutathione (GSH) to reduce or prevent tobacco smoke (TS)-induced cellular or macromolecular damage in the aerodigestive tract.” (see paragraph 0001 of Reznick). Therefore, an ordinary skilled artisan could “readily envisage” a combination of hydroxocobalamin and deferoxamine from this list, since this combination is only one of four possible combinations. Furthermore, the instant claims recite a composition “comprising” the hydroxocobalamin and deferoxamine, which means additional, unrecited elements such as the reduced glutathione in this list are not excluded and within scope of the instant composition. See MPEP 2111.03 I.
Applicant states that the instant application addresses a technical problem that is fundamentally different than Reznick. Applicant states that the instant application focuses on the immediate risk of mortality caused by smoke inhalation in fire scenarios, whereas Reznick focuses on chronic diseases of aerodigestive tract caused by tobacco smoke. Therefore, Applicant contends that these fundamental differences must be considered comprehensively.
Applicant’s argument described above was not found persuasive because instant claims 1-10 are directed toward a composition with the recited intended uses “for upper respiratory tract administration and for use in protection from fire caused by inhalation of toxic gas containing cyanide”.
As stated in MPEP 2111.02, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”, and “To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim.”
Here, the intended use “for upper respiratory tract administration” does limit the structure of the composition, however the composition of Reznick would be capable of upper respiratory tract administrations as Reznick discloses their compositions can be inhaled. Furthermore, the intended use “for use in protection from fire caused by inhalation of toxic gas containing cyanide” does not limit the structure of the recited composition because this intended use is a mere statement of purpose of use and is not considered a structural limitation for the recited composition. Therefore, Reznick teaches all of the structural limitations of the recited compositions and is capable of performing the recited intended use for upper respiratory tract administration.
Furthermore, MPEP 2144 IV states that “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant.”
Here, in regards to the 35 USC 103 rejection over Reznick, even if the instant composition and the combination of Reznick described above may have different technical effects, it is not necessary that the Reznick composition achieve the same technical effects to establish obviousness.
Applicant states that their combination of hydroxocobalamin and deferoxamine has a synergistic effect. Here, Applicant refers to Table 2, in which Example 1 (25mg hydroxocobalamin and 1mg deferoxamine) and Example 2 (125mg hydroxocobalamin and 5mg deferoxamine) increased the survival rates of mice exposed to cyanide by 22.0% and 88%, respectively, whereas Comparative 1 (25mg hydroxocobalamin) and Comparative 2 (5mg deferoxamine) had no increase in survival rates. Applicant states that the fact that a lower dosage of a component in combination outperforms a higher dosage of the same component alone is a classic hallmark of synergy.
In response to Applicant’s showing of an unexpected synergistic effect, the showing of an unexpected result cannot overcome a 35 USC 102 rejection, since the evidence is evaluated to determine nonobviousness for a 35 USC 103 rejection according to MPEP 716.01(a). However, assuming arguendo that there was no 35 USC 102 rejection, even though Reznick anticipates instant claims 1-2 and 5, this unexpected result must be compared to the closest prior art as stated in MPEP 716.02(e) in order to rebut a prima facie case of obviousness.
Here, the closest prior art is Reznick, which teaches either hydroxocobalamin or a combination of deferoxamine and reduced glutathione.
Furthermore, MPEP 716.02(e) states that “Showing unexpected results over one of two equally close prior art references will not rebut prima facie obviousness unless the teachings of the prior art references are sufficiently similar to each other that the testing of one showing unexpected results would provide the same information as to the other. In re Johnson, 747 F.2d 1456, 1461, 223 USPQ 1260, 1264 (Fed. Cir. 1984) (Claimed compounds differed from the prior art either by the presence of a trifluoromethyl group instead of a chloride radical, or by the presence of an unsaturated ester group instead of a saturated ester group. Although applicant compared the claimed invention with the prior art compound containing a chloride radical, the court found this evidence insufficient to rebut the prima facie case of obviousness because the evidence did not show relative effectiveness over all compounds of the closest prior art. An applicant does not have to test all the compounds taught by each reference, "[h]owever, where an applicant tests less than all cited compounds, the test must be sufficient to permit a conclusion respecting the relative effectiveness of applicant’s claimed compounds and the compounds of the closest prior art."
Here, while Applicant has demonstrated a synergistic effect over hydroxocobalamin and deferoxamine alone, Applicant has not provided evidence that this synergistic effect would also be unexpected over the Reznick composition of deferoxamine and reduced glutathione, since a comparison to this composition has not been provided, and Applicant’s comparison to hydroxocobalamin and deferoxamine alone is not sufficiently similar to the Renzick combination of deferoxamine and reduced glutathione to support the conclusion that the synergy result would also apply over this combination. Furthermore, Reznick demonstrates a synergistic effect when combining deferoxamine and reduced glutathione (see paragraphs 0225-0227 in Reznick), and the instant claims also recite a composition “comprising” the claimed compounds, which means additional, unrecited elements such as the reduced glutathione of Reznick are not excluded and within scope of the instant composition. See MPEP 2111.03 I. Therefore, Applicant has not provided sufficient evidence of an unexpected result to rebut the obviousness over Reznick.
Furthermore, Applicant’s showing of a synergistic effect is not commensurate in scope with the claims. Applicant has only demonstrated a synergistic effect with 25mg hydroxocobalamin and 1mg deferoxamine as well as 125mg hydroxocobalamin and 5mg deferoxamine, and claim 1 does not recite an amount or a ratio for the hydroxocobalamin and deferoxamine. Therefore, Applicant has not demonstrated a synergistic effect over the full scope of claim 1. It is also noted that the parts by weights recited in claims 8 and 10 also do not appear to be commensurate in scope because the synergistic effect was only demonstrated at 25 parts by weight hydroxocobalamin and 1 part by weight deferoxamine.
Applicant states that in regards to the rejection over claims 6 and 8, Choi provides no guidance regarding the amount of deferoxamine as Applicant contends that Choi explicitly states that the mitochondrial iron chelator does not comprise deferoxamine.
Applicant’s argument described above was not found persuasive because the new rejection over claims 6 and 8 now relies on Clements to arrive at the recited amounts of deferoxamine as described above and therefore renders the argument over Choi moot.
Furthermore, the rejection over claim 10 does rely on Choi to arrive at the amounts of metal iron chelators. Even though Choi teaches only using deferiprone, the teachings of Choi are only relied upon to establish an effective amount of iron chelators at 5-90% by weight as described above, and an ordinary skilled artisan could have performed routine optimization to modify the parts by weight of the iron chelators such as the deferoxamine disclosed in Reznick and the deferiprone disclosed in Choi to arrive at the claimed invention.
Conclusion
No claim is found allowable.
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.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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