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 .
Current Status
This action is responsive to the amended claims of 11/10/2025. Claims 8-10 and 12-19 are pending. Claims 18-19 are new. Claims 12-15 are withdrawn. Claims 8-10 and 16-19 have been examined on the merits.
Election/Restrictions
Applicant’s remarks/amendments of 11/10/2025 did not overcome all pending prior art rejections of the previous action (mailed 07/09/2025). Thus, the Markush search will not be further extended in this action.
The elected species remains vemurafenib.
The elected species reads on claims 8-10 and 16-19.
Claims 12-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/26/2025.
Priority
The effective filing date remains 12/08/2017.
Response to Arguments
Examiner acknowledges receipt of the amended claims and remarks of 11/10/2025; no new matter is found.
The 112(b) rejection of claim 17 regarding “the protein kinase inhibitor” is withdrawn since Applicant has amended claim 17 to depend from claim 16.
The 112(b) rejection of claims 16-17 regarding the language introducing the Markush group is withdrawn since Applicant has amended the language from open (“comprises”) to closed (“is”).
The 112(d) rejection of claim 17 regarding “the protein kinase inhibitor” is withdrawn since Applicant has amended claim 17 to depend from claim 16.
The 102 rejection of claims 8 and 10 over CORSON, evidenced by ALIC, is withdrawn because Applicant has amended claim 8 to recite the limitations of claim 11 which was not anticipated by this reference.
Note, Applicant argues that the instant invention directly inhibits formation of ZnPP to afford acute treatment of hemorrhagic stroke and that this is not derivable from CORSON. Examiner agrees that CORSON on its own does not teach the inhibition of ZnPP formation. However, note, the instant claim 8 is not limited to an acute treatment (i.e., acute & chronic treatment are embraced by the current drafting).
The 102 rejection of claims 8 and 10 over REGAN, evidenced by COLE, is withdrawn because Applicant has amended claim 8 to recite the limitations of claim 11 which was not anticipated by this reference.
The 103 rejection of claims 8-10 and 16-17 over CORSON, ALIC, KLAEGER, and GIBSON is withdrawn as it was presented in the previous action since Applicant has imported the limitations of claim 11 into independent claim 8. Previously, claims 8-10 and 16-17 did not require the limitations of claim 11; however, in view of Applicant’s amendments the rejection of these claims over CORSON, ALIC, KLAEGER, and GIBSON is modified, below. Specifically, these claims are now rolled up into the rejection addressed in the next paragraph.
The 103 rejection of claims 8 and 11 over CORSON, ALIC, KLAEGER, and BRAUN is maintained, but modified to account for the amendments made to claim 8. Claim 8 now recites the limitations of claim 11; however, the recitation in the amended claim 8 is slightly narrower than the original recitation in claim 11. Claim 8 recites the inhibitor “directly inhibits” ZnPP formation, whereas claim 11 did not originally recite “directly” but embraced both direct and indirect inhibition of ZnPP formation.
Applicant's arguments filed 11/10/2025 have been fully considered but they are not persuasive. Applicant argues that the characterization of BRAUN is incomplete and the full characterization fails to cure the deficiencies of the other prior art references. Applicant states BRAUN teaches ferrochelatase catalyzes ZnPP formation “In iron deficiency” and further teaches the use of ZnPP levels as a measure of iron-deficient erythropoiesis. Thus, applicant argues, BRAUN provides no teachings regarding inhibition of ferrochelatase to stop ZnPP formation and does not provide a nexus for the artisan to extrapolate the findings of BRAUN to the instant method of treating hemorrhagic stroke.
Examiner respectfully disagrees. In the instant rejection, BRAUN is applied akin to an evidentiary reference. BRAUN is used to teach that a catalytic activity of ferrochelatase is incorporation of Zn into protoporphyrin IX to form ZnPP – i.e., this is a known fact. The fact that BRAUN further teaches ZnPP may be used to track iron-deficient erythropoiesis does not detract from the teachings about ferrochelatase’s catalytic activity. Furthermore, the context in which BRAUN teaches this activity is, as Applicant points out, “iron-deficiency”. The artisan would recognize BRAUN as related art, especially in view of this teaching of BRAUN. Hemorrhagic stroke relates to iron-deficiency since a hemorrhage is the medical term for bleeding and often refers to excessive bleeding – i.e., the artisan would recognize both as relating to anemia. The fact that BRAUN teaches in the context of iron-deficiency does not remove it from the realm of art related to hemorrhagic stroke. Further, CORSON, KLAEGER, and BRAUN each relate to ferrochelatase, making them related art. Thus, BRAUN does provide a nexus from which the artisan would be able to extrapolate the teachings within to the other prior art references.
Moreover, KLAEGER teaches vemurafenib inhibits ferrochelatase completely and systemically (Pg. 1251 Left Col. P1) by binding in the PPIX pocket of ferrochelatase (Pg. 1250 Figure 5 description part (b)) to completely shut down the catalytic activity of ferrochelatase (Pg. 1249 Left Col. Last paragraph), see Pg. 14-15 of previous action. Thus, KLAEGER teaches all catalytic activity of ferrochelatase is shut down by binding of the catalytic pocket. Since the catalytic pocket is blocked by vemurafenib, Examiner maintains the artisan would expect any and all catalytic activity of ferrochelatase to be blocked, including that taught by BRAUN and especially any catalytic activity on protoporphyrin IX (PPIX).
Note, Applicant’s response did not provide any evidence of secondary consideration (e.g., unexpected results, declaration/affidavit from an expert, etc. – see MPEP 716). Such evidence may help to preclude Examiner from making/maintaining further 103 rejections such as this.
The 103 rejection of claims 8-9 over REGAN, COLE, and GIBSON is withdrawn since Applicant has imported the limitations of claim 11 into independent claim 8. The combined references do not teach the direct inhibition of protoporphyrin IX from combining with Zn to form ZnPP.
The 103 rejection of claims 8 and 11 over REGAN, COLE, and BRAUN is withdrawn in view of the amendments to claim 8. Claim 8 now recites “the composition administered in an amount effective to directly inhibit” formation of ZnPP. As discussed in the interview of 10/06/2025 (see Interview Summary mailed 10/14/2025) protoporphyrin-Fe/heme, as taught by REGAN & COLE, is a down-stream inhibitor of ferrochelatase (i.e., negative feedback) and therefore does not fall into the definition of a direct inhibitor of ZnPP formation. Even in view of the teachings of BRAUN, that ferrochelatase catalyzes ZnPP formation, the relevant art teaches that protoporphyrin-Fe/heme only inhibits ferrochelatase via negative feedback and thus is not a direct inhibitor. Therefore, the rejection is withdrawn.
Note, Applicant’s arguments regarding BRAUN are addressed in ¶15, above. These arguments are not the reason for the withdrawal of the rejection.
Response to Amendment
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 8-10 and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over:
CORSON (US 2016/0222388, published 08/04/2016; provided by Examiner 07/09/2025),
In view of:
ALIC (Alic, M., et al., 2015. Stroke. In Gale (Ed.), The Gale Encyclopedia of Senior Health (2nd ed.). Gale. Retrieved from https://search.credoreference.com/articles/Qm9va0FydGljbGU6NDcyMTg3?aid=279753on 07/01/2025; provided by Examiner 07/09/2025),
In view of:
KLAEGER (Klaeger, S., et al., ACS Chemical Biology, 02/10/2016, 11, 1245-1254, cited in IDS of 05/27/2022),
In view of:
BRAUN (Braun, J., Kidney Internation, 1999, 55, 57-60, cited in IDS of 05/27/2022), and
In further view of:
GIBSON (US 2015/0366848; cited by Examiner 07/09/2025).
Determining the Scope and Contents of the Prior Art:
CORSON teaches methods of inhibiting ferrochelatase as an antiangiogenic therapy (Pg. 1 P2). CORSON further teaches during numerous pathological processes angiogenesis occurs and the newly formed blood vessels are fragile (Pg. 1 P3). CORSON teaches a method of inhibiting angiogenesis in an individual in need comprising administering an agent that inhibits ferrochelatase to the individual (Pg. 8 claim 1); wherein the individual has stroke or non-ocular hemorrhage (Pg. 9 claim 10). CORSON further teaches the method comprising administering the agent in a pharmaceutical composition further comprising a carrier (Pg. 9 claim 5). CORSON further defines an individual in need as an individual at risk for or having angiogenesis, such as in stroke (Pg. 4 P35). Thus, the Examiner understands angiogenesis to be a symptom or clinical sign of stroke.
ALIC teaches there are two types of stroke: ischemic and hemorrhagic, wherein hemorrhagic strokes occur when a thin, weak spot in an artery bursts causing bleeding (hemorrhaging) in the brain (Pg. 1 Types of Stroke).
KLAEGER teaches ferrochelatase (FECH) is an off-target of the kinase inhibitor vemurafenib (Pg. 1245 abstract). KLAEGER teaches, of the 226 kinase inhibitors tested, vemurafenib was one of the top three most potent FECH inhibitors (Pg. 1247 Right Col. P2) with a Kd of 1.3 uM (Pg. 1248 Table 1). KLAEGER further teaches, with a dose of 960 mg twice daily, vemurafenib concentration in the human body is high enough to inhibit FECH completely and systemically (Pg. 1251 Left Col. P1).
BRAUN teaches ferrochelatase catalyzes the incorporation of zinc into protoporphyrin IX resulting in the formation of zinc protoporphyrin (ZnPP) (Pg. 57 Abstract).
GIBSON teaches cerebral cavernous malformation (CCM) is a stroke disorder associated with acute bleeding leading to inflammation and stroke (Pg. 1 P4). GIBSON teaches a method of preventing hemorrhage in a patient with at least one CCM lesion by administering a medicament (Pg. 2 P32). GIBSON also teaches 17% of CCM patients die due to intracerebral hemorrhages and these hemorrhages can result in significant impacts on an individual’s quality of life; individuals with multiple CCM lesions and/or those who have recently experienced hemorrhage have the highest risk of hemorrhage (Pg. 2 P31). Thus, the Examiner understands it is possible to administer a medicament before an intracerebral hemorrhage (i.e., hemorrhagic stroke) occurs in a patient.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
CORSON does not teach the stroke is specifically hemorrhagic stroke, the ferrochelatase inhibitor is vemurafenib, or administration before the subject manifests symptoms of a hemorrhagic stroke.
ALIC does not teach administration of a ferrochelatase inhibitor to a subject to treat hemorrhagic stroke.
KLAEGER does not teach administration of vemurafenib to a subject with or at risk of hemorrhagic stroke. Further, KLAEGER is silent as to the inhibition of ZnPP formation.
BRAUN does not teach administration of a ferrochelatase inhibitor to a subject to treat hemorrhagic stroke.
GIBSON does not teach administration of a ferrochelatase inhibitor.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of hemorrhagic stroke and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding stroke and ferrochelatase inhibition and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references CORSON, ALIC, KLAEGER, BRAUN, and GIBSON
Regarding claims 8-10 and 16-17, the artisan would find it obvious to treat a subject having or at risk of having hemorrhagic stroke by administering vemurafenib, a kinase inhibitor recognized by KLAEGER to inhibit FECH, to the subject either after or before the subject manifests a symptom of hemorrhagic stroke utilizing the method of CORSON, in view of ALIC and GIBSON. Thus, the artisan would need motivation to 1) treat hemorrhagic stroke (i.e., instant claim 8 and 10), 2) use vemurafenib as the FECH inhibitor (i.e., instant claim 16-17), and 3) treat a subject before manifestation of a symptom (i.e., instant claim 9). Further, the combined art would have to teach 4) the property of direct inhibition of ZnPP formation (i.e., instant claim 8).
1) The artisan would be motivated to treat hemorrhagic stroke using the method of CORSON, since there are only two types of stroke, as recognized by ALIC (Pg. 1 Types of Stroke), CORSON claims stroke as a disease necessitating therapy comprising administration of a pharmaceutical composition of a FECH inhibitor (Pg. 9 claims 5 & 10), and CORSON teaches angiogenesis as a symptom or clinical sign of stroke (Pg. 4 P35). Thus, the artisan would at once envisage the method of CORSON applied to treatment of hemorrhagic stroke. Furthermore, since ALIC teaches hemorrhagic strokes occur at thin, weak spots in arteries (Pg. 1 Types of Stroke) and CORSON teaches during numerous pathological processes angiogenesis occurs and the newly formed blood vessels are fragile (Pg. 1 P3), the artisan would recognize the overlap in fragile/weak/thin blood vessels between hemorrhagic stroke and the angiogenic stroke recited by CORSON. Thus, the artisan would have an expectation of success in treating hemorrhagic stroke with a FECH inhibitor (i.e., instant claims 8 and 10).
2) The artisan would be motivated to utilize vemurafenib as the FECH inhibitor since KLAEGER teaches vemurafenib is a potent FECH inhibitor (Pg. 1247 Right Col. P2) that inhibits FECH completely and systemically (Pg. 1251 Left Col. P1). Furthermore, it would have been obvious for the artisan to substitute one functional equivalence (any FECH inhibitor) for another (Vemurafenib) with an expectation of success, since the prior art establishes that both function in a similar manner, thus resulting in the practice of the instant claims 8, 10, and 16-17, with a reasonable expectation of success.
3) The artisan would be motivated to treat a subject at risk of having hemorrhagic stroke before manifestation of symptoms (i.e., instant claim 9) in order to reduce number of deaths and the significant impacts intracerebral hemorrhages have on an individual’s quality of life; as recognized by GIBSON (Pg. 2 P31). The artisan would recognize a subject with CCM lesions as an individual at risk of hemorrhage since GIBSON teaches individuals with multiple CCM lesions have the highest risk of intracerebral hemorrhage (Pg. 2 P31). Thus, the artisan would recognize the risk of hemorrhagic stroke in CCM patients and be motivated to administer the FECH inhibitor preemptively to reduce the negative outcomes of hemorrhage in this patient population. The artisan would have an expectation of success since GIBSON teaches administering a medicament before intracerebral hemorrhage (Pg. 2 P32) and since the method made obvious by CORSON, ALIC, and KLAEGER is useful for treatment of hemorrhagic stroke (i.e., intracerebral hemorrhage).
4) Instant claim 8 is drawn to a property of the pharmaceutical composition upon administration to the subject, i.e., the pharmaceutical composition is in an amount effective to directly inhibit the formation of ZnPP. This property would be expected for known clinical doses of vemurafenib, in view of KLAEGER and BRAUN. Since BRAUN teaches ferrochelatase catalyzes the formation of zinc protoporphyrin (ZnPP) (Pg. 57 Abstract), and since KLAEGER teaches vemurafenib binds in the PPIX pocket of FECH (Pg. 1250 Figure 5 description part (b)), causes elevated PPIX levels (Pg. 1251 Left Col. P1), and, with a dose of 960 mg twice daily, inhibits FECH completely (Pg. 1251 Left Col. P1) wherein this FECH inhibition leads to PPIX accumulation (Pg. 1251 Right Col. P1) and complete shutdown of the catalytic activity of the FECH (Pg. 1249 Left Col. Last paragraph), the artisan would recognize that inhibition of FECH would nullify the ability of FECH to catalyze the formation of ZnPP. Further, the accumulation of PPIX via complete shutdown of FECH via binding of the PPIX pocket would be understood as direct inhibition of FECH to catalyze anything involving PPIX. Thus, it would be obvious to the artisan that administration of a pharmaceutical composition comprising a FECH inhibitor, such as vemurafenib in a known clinical dose, would result in the direct inhibition of the formation of ZnPP.
Regarding claim 18, under the broadest reasonable interpretation, acute treatment is generally understood to be immediate, short-term medical treatment in response to a medical episode (i.e., it is not chronic care). Thus, Examiner understands acute treatment to include any administration of a medication in response to a patient experiencing a medical episode. Thus, the teaching of instant claims 8 and 10, above, (i.e., a method of treating hemorrhagic stroke after a symptom/sign) is understood as an acute treatment. Thus, the inhibition of FECH by vemurafenib, and the resulting property thereof which is inhibition of ZnPP formation, would provide acute treatment.
Claims 8 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over:
CORSON (US 2016/0222388, published 08/04/2016; provided by Examiner 07/09/2025),
ALIC (Alic, M., et al., 2015. Stroke. In Gale (Ed.), The Gale Encyclopedia of Senior Health (2nd ed.). Gale. Retrieved from https://search.credoreference.com/articles/Qm9va0FydGljbGU6NDcyMTg3?aid=279753on 07/01/2025; provided by Examiner 07/09/2025),
KLAEGER (Klaeger, S., et al., ACS Chemical Biology, 02/10/2016, 11, 1245-1254, cited in IDS of 05/27/2022),
BRAUN (Braun, J., Kidney Internation, 1999, 55, 57-60, cited in IDS of 05/27/2022), and
GIBSON (US 2015/0366848; cited by Examiner 07/09/2025)
as applied to claim 8 above, and further in view of:
ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53).
Determining the Scope and Contents of the Prior Art:
CORSON, ALIC, KLAEGER, BRAUN, and GIBSON teach the method of claim 8, see ¶22 above for the relevant teachings.
ALIC further teaches immediate treatment is aimed at preventing further damage to the brain and emergency treatment of hemorrhagic stroke is aimed at controlling bleeding (Pg. 5 Treatment ¶1 & 3). Further, prognosis depends on time elapsed between symptom onset and initiation of treatment wherein emergency treatment can significantly improve survival and recovery (Pg. 6 Prognosis ¶1).
ANSEL teaches the safe and effective dose of a drug depends on a number of factors including characteristics of the drug, the dosage form, and a variety of patient factors (Pg. 48 Left Col. para 2) and the effective dose may be different for different patients (Pg. 48 Left Col. para 4). ANSEL further teaches the schedule of dosage or the dosage regimen is determined based on a drug’s duration of action, pharmacokinetics, and characteristics of the dosage form (Pg. 40 Right Col. para 2).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
CORSON, ALIC, KLAEGER, BRAUN, and GIBSON do not teach detectable reduction of ZnPP in 24 hours post-treatment.
ANSEL does not teach a method of treating hemorrhagic stroke.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treating hemorrhagic stroke and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding vemurafenib dosages and optimization thereof and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references CORSON, ALIC, KLAEGER, BRAUN, GIBSON, and ANSEL.
MPEP 2112(IV) states: "‘[I]n order to rely on inherency to establish the existence of a claim limitation in the prior art in an obviousness analysis – the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art.’ Id. at 1195-96, 112 USPQ2d at 1952. But see, Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020).”
Since the prior art references together teach that vemurafenib shuts down all catalytic activity of FECH (KLAEGER Pg. 1249 Left Col. Last paragraph) and formation of ZnPP is catalyzed by FECH (Pg. 57 Abstract), the limitation of the instant claim that treatment reduces ZnPP formation is necessarily present in the prior art combination.
The reduction being measurable within 24-hours of treatment compared to an untreated patient is not necessarily present in the prior art combination.
However, the artisan would have been motivated to optimize the dosage regimen of vemurafenib to see treatment effects sooner rather than later. The artisan would be motivated to do so in order to improve prognosis, survivability, and recovery from the stroke, as recognized by ALIC (Pg. 6 Prognosis ¶1).
MPEP 2144.05(II)(A) provides guidance about the routine optimization of prior art conditions: "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").”
In the instant case, KLAEGER teaches a 960 mg twice daily dose of vemurafenib inhibits FECH completely and systemically (Pg. 1251 Left Col. P1). Since ANSEL teaches the dosage regimen is based on duration of action and pharmacokinetics (Pg. 40 Right Col. ¶2) and the effective dosing may be different for different patients (Pg. 48 Left Col. ¶4), the artisan would recognize the dosage regimen as a result-effective variable, i.e., a variable that achieves a recognized result – in this case, the inhibition of ferrochelatase. Thus, the dosage and resulting inhibition of ferrochelatase is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Therefore, the determination of the optimum or workable dosage regimen of vemurafenib which would achieve full inhibition of FECH would have been well within the practice of the artisan.
The artisan would expect to see a decrease in the PPIX-related catalytic products of FECH in response to this treatment since KLAEGER teaches vemurafenib binds in the PPIX pocket of FECH (Pg. 1250 Figure 5 description part (b)), causes elevated PPIX levels (Pg. 1251 Left Col. P1), and, this FECH inhibition leads to PPIX accumulation (Pg. 1251 Right Col. P1). Thus, the artisan would expect PPIX-related products, including ZnPP, to decrease after catalytic FECH inhibition. The time to detectable decrease (e.g., 24 hours) would be a function of the dosage regimen based on the analysis above. The decrease would necessarily be compared to an untreated subject since the treatment itself is what is expected to produce the decrease. Furthermore, absent any evidence demonstrating a patentable difference between the instant and prior art compositions and the criticality of the claimed dosage regimen, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Conclusion
Claims 8-10 and 16-19 are rejected.
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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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625