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 .
DETAILED ACTION
This Office Action is responsive to the Response to Election/Restriction filed 11/05/2025.
The preliminary amendment filed 07/10/2023, cancelled claims 2 and 15, and amended claims 3-4 and 16-23.
Claims 1, 3-14, and 16-23 are pending.
Priority
This application claims the following priority:
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Election/Restrictions
Applicant's election with traverse of a) inflammatory disease as the species of disease, and b) senicapoc, an inhibitor of the Gardos channel, as the species of compound, in the reply filed on 11/05/2025, is acknowledged. The traversal is on the grounds that the present claims do not simply recite the treatment of anemia, but the treatment of anemia of inflammation, which is not the anemia occurring in sickle cell disease, as taught by Brugnara (pg. 3, Remarks).
This is not found persuasive because sickle cell disease is a chronic anemic inflammatory disease, as evidenced by Bandiera (Chronic inflammatory state in sickle cell anemia patients is associated with HBB*S haplotype, PTO-892). As such, the patient population of the patients in Brugnara includes patients with both anemia from sickle cell disease and patients with anemia of inflammation.
On pg. 3, Remarks, Applicant further argues that “The presently claimed invention for the first time discloses that chemokines induce Ca2+ influx in healthy erythrocytes leading to erythrocyte dehydration. . .These findings provide a scientific basis for the prevention of chemokine-mediated erythrocyte dehydration in patients that suffer from anemia of inflammation,” which is in contrast to Brugnara which describes treatment of sickle cell anemia patients with clotrimazole.
This argument has been fully considered, but is not found persuasive. The instant claims are not directed toward “chemokines induc(ing) Ca2+ influx in healthy erythrocytes leading to erythrocyte dehydration,” but are directed toward a method of treating or preventing anemia of inflammation by administering a therapeutically effective amount of a compound selected from the group consisting of a) an inhibitor of Ca2+ -activated potassium channel; b) an inhibitor of interaction of one or more chemokines with Duffy antigen receptor for chemokines; and c) a compound that inhibits activation of adhesion molecules expressed on erythrocytes. Brugnara teaches a method of treating sickle cell disease, which is a chronic inflammatory disease of anemia, by administering clotrimazole, a Ca2+ activated potassium Gardos channel inhibitor. As such, Brugnara teaches the instantly claimed technical feature. See pg. 4 of the 09/05/2025, Restriction Requirement.
The requirement is still deemed proper and is therefore made FINAL.
Claims 5-9, 11, and 20-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected subject matter, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 11/05/2025.
Claims 1, 3-4, 10, 12-14, 16-19 and 23 are pending and examined on the merits herein.
Claim Objections
Claims 1, 14, 16, and 23 are objected to because of the following informalities:
-In claim 1, line 4, in claim 14, line 4, and in claim 23, line 2, the limitation "the Ca2+ -activated potassium channel" should be replaced with “a Ca2+ -activated potassium channel."
-In claims 16, line 2, following “inflammation is,” the phrase - -caused by- - should be inserted.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1, 10, 12-14, 16-17, and 23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
-In claims 1, 14, and 23, lines 4, 4, and 2-3, respectively, the phrase “(Gardos channel)” renders the claims indefinite, as it is not clear if “Gardos channel” is limiting the Ca2+ -activated potassium channel to a “Gardos channel” or if “Gardos channel” is merely exemplary of a preferred Ca2+ -activated potassium channel.
In view of compact prosecution, for the purpose of applying prior art, “Gardos channel” is interpreted as merely exemplary of Ca2+ -activated potassium channel.
-Regarding claims 10 and 13, lines 4 and 3, respectively, the phrase "such as" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention, or merely exemplary. See MPEP § 2173.05(d).
All other claims not specifically recited are rejected for depending from an indefinite claim and failing to cure the deficiency.
Claim Rejections - 35 USC § 112(a)-Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, 10, 12-14, 16-19 and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting the adhesion of red blood cells in patients with sepsis by administering a therapeutically effective amount of TRAM-34 or an anti-Darc antibody, does not reasonably provide enablement for a method for the treatment or prevention of anemia of inflammation comprising administering to a subject a therapeutically effect amount of a compound selected from the group consisting of a) an inhibitor of Ca2+ -activated potassium channel; b) an inhibitor of interaction of one or more chemokines with Duffy antigen receptor for chemokines, and c) a compound that inhibits activation of adhesion molecules expressed on erythrocytes. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Independent claim 1 is directed toward a method for the treatment or prevention of anemia of inflammation, caused by any condition or disease, comprising administering to a subject a therapeutically effect amount of a compound selected from the group consisting of a) any inhibitor of Ca2+ -activated potassium channel; b) any inhibitor of interaction of one or more chemokines with Duffy antigen receptor for chemokines, and c) any compound that inhibits activation of adhesion molecules expressed on erythrocytes.
As such, given the great breadth and variety of the patient population in combination with the great breadth of the compounds, the breadth of the claim is great.
Level of Skill in Art
The level of skill in the art is a clinician or a scientist with a PhD.
State of the Prior Art
Weiss (Anemia of Inflammation, Blood, published 2019, PTO-892) teaches that anemia of inflammation (AI) is also referred to as anemia of chronic disease, and that it develops from systemic inflammation due to decreased production of erythrocytes accompanied by a modest reduction in erythrocyte survival (abstract).
On pgs. 43-45, Weiss teaches that it is challenging to diagnosis AI and that there is still a need for readily available and interpretable biomarkers that clearly differentiate between AI and iron deficiency anemia patients, to identify the best therapy and predict the therapeutic response.
Weiss teaches that when treating anemias, one has to consider whether such a treatment also impacts the underlying disease, which is of utmost concern when treating patients with infections or cancer (pg. 45).
Weiss teaches that the best treatment for AI is to cure the underlying inflammatory disease, i.e., treatments that target the infectious or inflammatory processes that causes anemia of inflammation will not only ameliorate the anemia but also improve many symptoms and deficits caused by the primary disease (pg. 46). “However, such fundamental treatments are not always possible or effective. With regard to treatments directed specifically at AI, we lack data from prospective trials about how aggressive such treatments should be or what constitutes the optimal therapeutic end point” (pg. 46).
Weiss teaches that two therapies have been established for the treatment of AI—iron supplementation and treatment with erythropoiesis-stimulating agents (ESAs), and that red blood cell transfusion is considered only as an emergency treatment in patients with severe anemia who are clinically unstable (pg. 46). However, concerns about the unrestricted use of ESAs in AI arose from studies showing higher mortality in patients with cancer or in dialysis (pg. 46).
Weiss teaches that prolyl hydroxylase inhibitors, which stabilize hypoxia-inducible factors, are being studied for the treatment of AI.
Weiss concludes by stating that “Our knowledge on the pathophysiology of AI has expanded dramatically over the past years, and we are gathering information on the therapeutic efficacy of established and novel emerging treatment strategies. However, we are still lacking information on optimal therapeutic start and end points for AI and are in need of identifying biomarkers that help to differentiate patients with AI from patients with iron deficiency” (pg. 47).
NIH (Anemia of Inflammation or Chronic Disease, PTO-892) teaches that experts have not yet found a way to prevent anemia of inflammation (pg. 5). NIH further teaches that health care professionals typically treat anemia of inflammation by treating the underlying condition (pg. 5). NIH additionally teaches that the anemia can be treated with erythropoiesis-stimulating agents and blood transfusions, in severe cases (pg. 5).
WO 00/50026 to McNaughton-Smith (published 2000, PTO-892) teaches a method for treating or preventing a sickle cell disease event, said method comprising administering to a subject suffering from sickle cell disease:
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, senicapoc (claims 18-21), wherein McNaughton-Smith teaches senicapoc as a Gardos channel antagonist that inhibits the Gardos channel (title, abstract, pg. 5, lines 11-21; pg. 6, lines 13-21 pg. 11, Table 1).
In summary, the prior art teaches that anemia of inflammation is challenging to diagnose and that the best treatment is the treatment of the underlying disease causing the anemia of inflammation. The prior art additionally teaches that there are only a couple of treatments known for anemia of inflammation, iron supplementation and treatment with erythropoiesis-stimulating agents. The prior art teaches that preventing anemia of inflammation is not known. And the prior art teaches that Gardos channel inhibitors, such as senicapoc, are known for the treatment of sickle cell anemia.
Predictability in the Art
Weiss teaches that:
-it is challenging to diagnosis AI and that there is still a need for readily available and interpretable biomarkers that clearly differentiate between AI and iron deficiency anemia patients, to identify the best therapy and predict the therapeutic response;
-when treating anemias, one has to consider whether such a treatment also impacts the underlying disease, which is of utmost concern when treating patients with infections or cancer;
-with regard to treatments directed specifically at AI, data is lacking from prospective trials about how aggressive such treatments should be or what constitutes the optimal therapeutic end point” (pg. 46);
-there are only two known therapies for AI; and
-“we are still lacking information on optimal therapeutic start and end points for AI.”
In view of the teachings of Weiss, the art of diagnosing and treating anemia of inflammation is unpredictable.
Working Examples
Example 1, beginning on pg. 22 studies the adhesion of donor RBC to laminin-alpha5 in response to IL-8 and sera from sepsis patients. For determining the effect of TRAM34, donor RBCs were first incubated with TRAM34 and then with IL-8 prior to the adhesion assay. For determining the effect of serum of sepsis patients, donor RBCs were first incubated with TRAM34 or anti-DARC antibodies and then with sera of sepsis patients (pg. 23).
Example 1 states that in AI, erythropoiesis is decreased and RBC destruction is exacerbated (pg. 24). The increased RBC destruction in AI is attributed to inflammation mediated hyperactivation of splenic macrophages. Incubation of RBCs with IL-8 induces a transient DARC-dependent rise of intracellular calcium levels in a subset of RBCs. This shows a direct effect of this pro-inflammatory chemokine on the integrity of RBCs, which may contribute to their degradation (pg. 25, Fig. 6). SDF-1, a chemokine, combined with IL-8 induces an even stronger calcium influx causing exacerbated loss of RBC deformability, leading to activation of adhesion molecules (pgs. 25-26). This data, indicates that healthy RBCs are targeted for destruction upon binding of IL-8 to DARN, contributing to the rapid decrease of circulating RBCs, which is what is observed in AI. Example 1 hypothesizes that the IL-8 dependent signaling response that is elicited in RBCs similarly occurs in erythroblasts, such that chronic inflammation may substantially impact erythropoiesis through DARC-mediated signaling (Fig. 7, pg. 26).
Pg. 26, lines 15-17 state, “In summary, we hypothesize that DARC-mediated signaling contributes to increased breakdown of RBC as well as to the inhibition of erythropoiesis in AI.”
Next the effect of an inhibitor of the Gardos channel in response to proinflammatory chemokines was assessed (pg. 26). The interaction between adhesion molecules and laminin-alpha5 and/or hyaluronic acid is assessed as a measure of RBC dehydration.
Erythrocyte adhesion to laminin-alpha5 and hyaluronic acid in response to IL-8 and sera of sepsis patients was assessed in the absence and presence of TRAM34, an inhibitor of the Gardos channel. Adhesion of donor RBCs in response to IL-8 incubation and sera of sepsis patients is inhibited by TRAM34 and anti-DARC antibodies (Fig. 8B, 8C pgs. 26-27).
Example 2, beginning on pg. 27, uses a mouse model in studying the efficacy of senicapoc on anemia of inflammation. However, this example is a prophetic example and the results are hypothesized.
Direction and Guidance
In view of the unpredictability of the art and the lack of working examples, the specification lacks sufficient direction and guidance to enable an ordinary skilled artisan to make and use the instant invention as claimed.
Quantity of Experimentation
In view of the lack of working examples, the unpredictability of the art, and the great breadth of the claims, the amount of experimentation required to determine which inhibitors of Ca2+ -activated potassium channel; which inhibitors of interaction of one or more chemokines with Duffy antigen receptor for chemokines, and which compounds that inhibits activation of adhesion molecules expressed on erythrocytes, are effective in treating anemia of inflammation caused by which diseases, would be astronomical. This amount of experimentation would require starting at proof-of-concept, and proceeding through all levels of lead identification and optimization, This amounts to invention, not development; it is an undue amount of experimentation.
Thus, while being enabling for a method of inhibiting the adhesion of red blood cells in patients with sepsis by administering a therapeutically effective amount of TRAM-34 or an anti-Darc antibody, the instant specification does not reasonably provide enablement for a method for the treatment or prevention of anemia of inflammation comprising administering to a subject a therapeutically effect amount of a compound selected from the group consisting of a) an inhibitor of Ca2+ -activated potassium channel; b) an inhibitor of interaction of one or more chemokines with Duffy antigen receptor for chemokines, and c) a compound that inhibits activation of adhesion molecules expressed on erythrocytes.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-4, 10, 13-14, 16, 18-19 and 23 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over WO 00/50026 to McNaughton-Smith (published 2000, PTO-892), as evidenced by Bandeira (Chronic inflammatory state in sickle cell anemia patients is associated with HBB*S haplotype, Cytokine 65, published 2014, PTO-892) and Weiss (Anemia of Inflammation, Blood, published 2019, PTO-892).
McNaughton-Smith teaches a method for treating or preventing a sickle cell disease event, said method comprising administering to a subject suffering from sickle cell disease:
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, senicapoc (claims 18-21).
McNaughton-Smith teaches senicapoc as a Gardos channel antagonist that inhibits the Gardos channel (title, abstract, pg. 5, lines 11-21; pg. 6, lines 13-21 pg. 11, Table 1).
As evidenced by Bandeira, sickle cell anemia patients are in a chronic inflammatory state (title, abstract).
As evidenced by Weiss, anemia of inflammation (AI) is an anemia of chronic disease, and is caused by inflammatory diseases (abstract, pg. 41, Table 1).
While McNaughton-Smith does not explicitly teach “treatment or prevention of anemia of inflammation,” it is reasonable to assume that the method of McNaughton-Smith, which teaches administering the same compound, senicapoc, an inhibitor of Ca2+ -activated potassium channel, to the same patient population (patients with a chronic inflammatory disease) in therapeutically effective amounts, as that taught by the instant specification and claims, would have the same properties as the instantly claimed invention. Thus, while the prior art does not explicitly teach its method for “the treatment or prevention of anaemia of inflammation,” burden is on Applicant to show that the prior art does not have these properties. See MPEP 2112.02.
Moreover, since the instant claims recite “prevention of anemia of inflammation,” the patient population of the instant claims does not require patients to have anemia of inflammation. As such, the methods of McNaughton-Smith would necessarily prevent anemia of inflammation in patients with sickle cell disease.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claims 3-4, senicapoc is an inhibitor of the Gardos channel.
Regarding claim 10’s “wherein” clause, MPEP 2111.04 states, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the instant case, the wherein clause expresses the desired result of the positive step of administering senicapoc, an inhibitor of Ca2+ -activated potassium channel, to a patient with anemia of inflammation or a patient in need of prevention of anemia of inflammation. As such, the method of McNaughton-Smith meets the limitations of this claim.
Regarding claims 13, as evidenced by Bandeira, sickle cell anemia is an inflammatory disease.
Regarding claims 14 and 23, while McNaughton-Smith, does not explicitly teach “reducing or preventing erythrocyte dehydration in a subject suffering from chronic inflammation,” or “inhibiting potassium efflux from erythrocytes via the Ca2+ -activated potassium channel,” it is reasonable to assume that the method of McNaughton-Smith, which teaches administering a therapeutically effective amount of the same compound, senicapoc, an inhibitor of Ca2+ -activated potassium channel, to the same patient population as that taught by the instant specification and claims, would have the same properties as the instantly claimed invention. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties. See MPEP 2112.02.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claims 16, as evidenced by Bandeira, sickle cell anemia is an inflammatory disease.
Regarding claims 18-19, senicapoc is an inhibitor of the Gardos channel.
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 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 1, 3-4, 10, 13-14, 16, 18-19, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over WO 00/50026 to McNaughton-Smith (published 2000, PTO-892) in view of Bandeira (Chronic inflammatory state in sickle cell anemia patients is associated with HBB*S haplotype, Cytokine 65, published 2014, PTO-892) and Weiss (Anemia of Inflammation, Blood, published 2019, PTO-892).
McNaughton-Smith teaches a method for treating or preventing a sickle cell disease event, said method comprising administering to a subject suffering from sickle cell disease:
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, senicapoc (claims 18-21).
McNaughton-Smith teaches senicapoc as a Gardos channel antagonist that inhibits the Gardos channel (title, abstract, pg. 5, lines 11-21; pg. 6, lines 13-21 pg. 11, Table 1).
Regarding claim 1, while McNaughton-Smith teaches a method of treating sickle cell anemia by administering senicapoc, an inhibitor of Ca2+ -activated potassium channel, it differs from that of instant claim 1 in that it does not teach the treatment or prevention of anemia of inflammation.
Bandeira teaches sickle cell anemia patients as in a chronic inflammatory state (title, abstract). Bandeira teaches that sickle cell anemia patients have an increased inflammatory profile compared to healthy individuals. Bandeira teaches that inflammation plays a significant role in the clinic in sickle cell disease, and the endothelium plays a critical role in propagation and perpetuation of the chronic inflammatory state that characterizes sickle cell anemia. The cytokines and chemokines produced by the activated endothelium contribute to the pan-cellular activation that results in the high circulating levels of the numerous inflammatory molecules encountered in sickle cell anemia patients, such as TNF-alpha, IL-6, and IL-17. These cytokines produced during inflammatory stress are also potent activators of the endothelium, and effect that creates the vicious circle leading to the perpetuation of inflammatory mediator production, cell adhesion to the vascular wall, and eventually chronic inflammation (pg. 219, Col. 2 “Discussion”).
Weiss teaches that anemia of inflammation (AI) is also known as anemia of chronic disease and is regarded as the most frequent anemia in chronically ill patients (title, abstract). Inflammatory diseases is a disease group in which AI is common (pg. 41, Table 1). Although not specifically documented AI is caused by three major pathophysiological pathways that act through mediators of an activated immune system (pg. 40, Col. 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select anemia of inflammation as additionally treated or prevented in the sickle cell patients of McNaughton-Smith, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- McNaughton-Smith teaches a method of treating sickle cell anemia,
- Bandeira teaches sickle cell anemia patients as in a chronic inflammatory state, and
-Weiss teaches that anemia of inflammation (AI) as an anemia of chronic disease, wherein inflammatory diseases are common anemias of inflammation.
As such, an ordinary skilled artisan would reasonably expect that the patients with sickle cell anemia in McNaughton-Smith, a chronic inflammatory disease, would also have anemia of inflammation, i.e., the patient population of sickle cell anemia patients, or be in need of the prevention of anemia of inflammation. Since the patient population of McNaughton-Smith is reasonably expected to comprise patients with both sickle cell anemia and anemia of inflammation, or require the prevention of anemia of inflammation, and since McNaughton-Smith teaches administering senicapoc to this patient population, the methods of McNaughton-Smith would reasonably be expected to treat or prevent anemia of inflammation. See MPEP 2112.02.
Regarding claims 3-4, senicapoc is an inhibitor of the Gardos channel.
Regarding claim 10’s “wherein” clause, MPEP 2111.04 states, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the instant case, the wherein clause expresses the desired result of the positive step of administering senicapoc, an inhibitor of Ca2+ -activated potassium channel, to a patient with anemia of inflammation. As such the combined method of McNaughton-Smith, Bandeira, and Weiss meets the limitations of this claim.
Regarding claims 13, as taught by Bandeira, sickle cell anemia is an inflammatory disease.
Regarding claims 14 and 23, while the combination of McNaughton-Smith, Bandeira, and Weiss, does not explicitly teach “reducing or preventing erythrocyte dehydration in a subject suffering from chronic inflammation,” or “inhibiting potassium efflux from erythrocytes via the Ca2+ -activated potassium channel,” it is reasonable to assume that the combined method of McNaughton-Smith, Bandeira, and Weiss, which teaches administering the same compound, senicapoc, an inhibitor of Ca2+ -activated potassium channel, in therapeutically effective amounts, to the same patient population, as that taught by the instant specification and claims, would have the same properties. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties. See MPEP 2112.02.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claims 16, as taught by Bandeira, sickle cell anemia is an inflammatory disease.
Regarding claims 18-19, senicapoc is an inhibitor of the Gardos channel.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over WO 00/50026 to McNaughton-Smith (published 2000, PTO-892) in view of Bandeira (Chronic inflammatory state in sickle cell anemia patients is associated with HBB*S haplotype, Cytokine 65, published 2014, PTO-892) and Weiss (Anemia of Inflammation, Blood, published 2019, PTO-892) as applied to claims 1, 3-4, 10, 13-14, 16, 18-19 and 23 above, and further in view of Swerdlow (Red Cell Exchange in Sickle Cell Disease, American Society of Hematology, published 2006, PTO-892).
McNaughton-Smith, Bandeira, and Weiss are applied as discussed above and incorporated herein.
While the combination of McNaughton-Smith, Bandeira, and Weiss teaches a method of treating or preventing anemia of inflammation in sickle cell anemia patient by administering senicapoc, it differs from that of instant claim 12, in that it does not teach erythrocyte transfusion.
Swerdlow teaches that red cell exchange transfusions, wherein patients’ red cells are removed and replaced by exogenous normal red cells, remain an effective therapy in acute and chronic treatment of sickle cell disease, wherein red cell exchange provides needed oxygen carry capacity while reducing the overall viscosity of blood (title, abstract). Red cell exchange is most useful in situations where it is important not just to provide oxygen carrying capacity but to decrease immediate complications of sickle cell disease. Red cell exchange also rapidly decreases the rate of hemolysis which can decrease liver processing of bilirubin, damage to renal tubular cells and the scavenging of nitric oxide by free hemoglobin released from sickle cells (pg. 49, Col. 2, 1st full paragraph). Red cell exchange can be accomplished by bleeding and infusing red cells manually or more efficiently through the use of an apheresis machine which spins blood to separate the plasma from cells.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add red cell exchange, to the combined method of McNaughton-Smith, Bandeira, and Weiss, to arrive at instant claim 12. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-the combined method of McNaughton-Smith, Bandeira, and Weiss teaches treating anemia of inflammation in sickle cell patients, and
-Swerdlow teaches red blood cell exchange effective therapy in acute and chronic treatment of sickle cell disease to increase oxygen carrying capacity, decrease the viscosity of the blood, and decrease immediate complications of sickle cell disease.
As such, an ordinary skilled artisan would have been motivated to make such an addition to predictably arrive at a method that more effectively treats sickle cell disease.
Applicant is reminded 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. See MPEP 2144 (IV).
Claims 1, 3, 10, 13-14, 16-18 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. 4,438,129 to McGraw (published 1984, PTO-892), in view of Bennett (Inflammation and Reactivation of Latent Herpesviruses in Older Adults, published 2013, PTO-892) and Weiss (Anemia of Inflammation, Blood, published 2019, PTO-892).
McGraw teaches the use of clotrimazole to treat herpes labialis. Specifically, McGraw teaches a method of treating the herpes simplex virus-I, by administering to an animal a therapeutically effective amount of a composition to alleviate the symptoms of the virus, wherein the composition comprises 1(o-chloro-α,α-diphenylbenzyl)imidazole, which is clotrimazole (abstract; Col. 4, claims 1-2).
McGraw teaches herpes labialis as an acute and recurring painful vesicular eruption of the oral mucosa in the vermillion borders of the lips. The causative agent is herpes virus type I, and the initial infection usually occurs in childhood. Mild trauma may be a predisposing factor for a recurrent eruption. As such, herpes labialis is a chronic disease.
Regarding claim 1, while McGraw teaches a method of treating HSV-I, and specifically herpes labialis, a chronic recurring infection, by administering clotrimazole, an inhibitor of Ca2+ -activated potassium Gardos channel, it differs from that of instant claim 1 in that it does not teach the treatment or prevention of anemia of inflammation.
Bennett teaches that inflammation increases with age and is associated with many chronic diseases, such as latent herpesviruses (abstract). Persistent pathogens that are acquired across the lifespan include herpesviruses. Being previously infected with multiple persistent pathogens does not always lead to symptomatic illness, however, individuals with a greater pathogen burden have high C-reactive protein and interleukin-6 levels. Thus, Bennett teaches that greater pathogen burden is linked to higher inflammation (Introduction, 2nd-4th paragraphs).
Weiss teaches that anemia of inflammation (AI) is also known as anemia of chronic disease (title, abstract). Infections are a disease group in which AI is common (pg. 41, Table 1). Although not specifically documented AI is caused by three major pathophysiological pathways that act through mediators of an activated immune system (pg. 40, Col. 2).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select anemia of inflammation as additionally treated or prevented by the methods of McGraw, to arrive at instant claim 1. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
- McGraw teaches a method of treating HSV-I in herpes labialis, wherein HSV-I is a recurring infection,
- Bennett teaches that inflammation increases with age in chronic diseases, such as latent herpesviruses, and
-Weiss teaches that anemia of inflammation (AI) is an anemia of chronic disease, wherein infections are common anemias of inflammation.
As such, an ordinary skilled artisan would reasonably expect that patients with recurrent HSV-I infection, which results in a chronic inflammatory disease, would also have anemia of inflammation or be in need of the prevention of anemia of inflammation. Thus, the patient population of McGraw is reasonably expected to comprise patients that require the prevention of anemia of inflammation, and since McGraw teaches administering clotrimazole to this patient population, the methods of McGraw would reasonably be expected to prevent anemia of inflammation. See MPEP 2112.02.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claim 3, clotrimazole is an inhibitor of the Gardos channel.
Regarding claim 10’s “wherein” clause, MPEP 2111.04 states, a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the instant case, the wherein clause expresses the desired result of the positive step of administering clotrimazole, an inhibitor of Ca2+ -activated potassium Gardos channel, to a patient with anemia of inflammation. As such the method of McGraw meets the limitations of this claim.
Regarding claims 13, herpes simplex virus is a viral infection. As evidenced by pgs. 1, 3, 7, and 8, of the instant specification, viral infections are inflammatory diseases.
Regarding claims 14 and 23, while McGraw, does not explicitly teach “reducing or preventing erythrocyte dehydration in a subject suffering from chronic inflammation,” or “inhibiting potassium efflux from erythrocytes via the Ca2+ -activated potassium channel,” it is reasonable to assume that the method of McGraw, which teaches administering the same compound, clotrimazole, an inhibitor of Ca2+ -activated potassium Gardos channel, in therapeutically effective amounts, to the same patient population, as that taught by the instant specification and claims, would have the same properties as the instantly claimed invention. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties. See MPEP 2112.02.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claims 16-17, herpes simplex virus is a viral infection. As evidenced by pgs. 1, 3, 7, and 8, of the instant specification, viral infections are inflammatory diseases.
Regarding claim 18, clotrimazole is an inhibitor of the Gardos channel.
Conclusion
No claims are allowed.
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/LAUREN WELLS/Examiner, Art Unit 1622