DETAILED ACTION
Status of Claims
Claims 1-6, 8-11, 13, 15-21, 28 and 30 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Office Action: Non-Final
Claim Objections
The following claims are objected to because of the following informalities:
A. Claim 1 is objected to because the claim should read:
1. ([…]) A method for prevention and/or treatment of oral mucositis in a patient in need thereof, wherein the patient is treated with a once-weekly regimen of 30 to [[-]]40 mg/m2 of cisplatin, comprising, administering to the patient, a composition comprising extracts from the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica.
B. Claim 28 is objected to because the first recitation of “MTS score” should be spelled completely, followed by a parenthetical acronym, e.g., “Mouth and Throat Soreness (MTS) score,” with subsequent recitations of the acronym, alone.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112, First Paragraph - 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 1-6, 8-11 and 13 are rejected under 35 U.S.C. § 112(a) or 35 U.S.C. § 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Scope of Enablement
Claim 1 is rejected under 35 U.S.C. § 112(a), because the specification, while being enabling for treating some kinds of “oral mucositis” in a “patient [that] is treated with a once-weekly regimen of 30-40 mg/m2 of cisplatin” does not reasonably provide enablement for “prevention” of said “oral mucositis.” The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Specifically, the method of preventing said “oral mucositis” has not been sufficiently taught to enable the full scope of the claims. In this regard, the application disclosure and claims have been compared per the factors indicated in the decision In re Wands, 8 USPQ 2d 1400 (Fed. Cir., 1988) as to undue experimentation. The factors include:
(1) the nature of the invention;
(2) the scope or breadth of the claims;
(3) the state of the prior art;
(4) the predictability or unpredictability of the art;
(5) the relative skill of those skilled in the art;
(6) the presence or absence of working examples;
(7) the amount of direction or guidance presented and,
(8) the quantity of experimentation necessary.
The relevant factors are addressed below on the basis of comparison of the disclosure, the claims and the state of the prior art in the assessment of undue experimentation.
(1) Nature of the Invention & (2) Scope or Breadth of the Claims:
Instant claim 1 recites:
1. ([…]) A method for prevention and/or treatment of oral mucositis in a patient in need thereof, wherein the patient is treated with a once-weekly regimen of 30-40 mg/m2 of cisplatin, comprising, administering to the patient, a composition comprising extracts from the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica.
However, the instant specification as originally filed lacks adequate guidance, direction or discussion to apprise the skilled artisan of how to prevent “oral mucositis” in a “patient [that] is treated with a once-weekly regimen of 30-40 mg/m2 of cisplatin.” The claims are broad in that they claim a method for preventing said “oral mucositis,” the breadth of which exacerbates the complexity of the invention. The term “prevention” is a potent and absolute term indicating that the method of prevention will necessarily prevent the onset of any of said “oral mucositis,” regardless of the cause, and in every instance by the administration of an effective amount of the composition of the instant method. Since the instant specification provides no limiting definition of the term “prevention,” the term has been interpreted expansively. The term “prevention” encompasses a wide range of situations, from preventing a disease or condition from occurring to preventing it from progressing. Nor is the term limited by any time frame.
Applicant is claiming a method of “prevention” of said “oral mucositis” in claim 1. Prevention, as defined by Merriam-Webster Dictionary, is to keep from happening or existing, which implies taking advance measures against something possible or probable. Furthermore, the act of preventing embraces complete 100% inhibition. Thus, the burden of enablement in the assertion of this claim is much higher than would be the case of enabling simply the treatment of the condition. As for the instant application in relation to the prior art, neither the prior art nor the instant application enable for prevention of said “oral mucositis.” Nowhere in the instant application has the efficacy of the composition of the instant method been enabled to prevent the occurrence of said “oral mucositis.” Since absolute success in preventing most diseases/conditions is not reasonably possible, the specification, which lacks an objective showing that said “oral mucositis” can actually be prevented, is viewed as lacking an adequate written description of the same.
The claim is thus extremely broad insofar as it suggests that following administration of the composition of the instant method, one will not experience said “oral mucositis”; that should one already have said “oral mucositis,” it will not worsen; and that it will not recur in any other cells of the body. For instance, the full scope of the claim encompasses the situation where administration of the composition of the instant method necessarily requires that any cell of the body on that individual will never experience said “oral mucositis” from the time of the administration forward. While such prevention might theoretically be possible under strictly controlled laboratory conditions, as a practical matter it is nearly impossible to achieve in the “real world” in which patients live.
(3) State of the prior art
The composition of the instant claims, particularly for treating said “oral mucositis” is known. See, for instance, US 2015/0064291 A1 by Rosenbluh et al., at abstract. Thus, the state of the art with regard to using the composition of the instant claims to prevent said “oral mucositis” is essentially non-existent. Examples of preventing said “oral mucositis” have not been described in the art.
(4) Degree of Predictability or Unpredictability in the Art
The ability to prevent said “oral mucositis” assumes that one is able to know where said “oral mucositis” will occur before it occurs. Accurate, reliable, and reproducible prediction of where said “oral mucositis” will occur on a mammal has not been demonstrated and is therefore highly unpredictable at this time.
(5) Relative Skill Possessed by Those in the Art
In view of the discussion of the state and predictability of the prior art, and the scope of the claims, which are drawn to a method of preventing “oral mucositis,” the level of skill in the art is high and is at least that of a medical doctor or Ph.D. scientist with several years of experience in the field(s) of oncology.
(6) Presence or Absence of Working Examples
No working examples of preventing said “oral mucositis” were provided since the instant published specification, US 2023/0390350 A1, Ex. 3, at par. [0023]-[0040], describes the use of the composition of the instant method “for the prevention of chemoradiation-induced oral mucositis (OM) in patients with head and neck cancer,” but not “prevention” in the absolute meaning of the word “prevent,” but instead, the data in Table 1 through Table 6 show treatment.
(7) Amount of Guidance or Direction Provided
In considering the guidance provided in the instant published specification, US 2023/0390350 A1, Ex. 3, at par. [0023]-[0040], describes the use of the composition of the instant method “for the prevention of chemoradiation-induced oral mucositis (OM) in patients with head and neck cancer,” while the data in Table 1 through Table 6 show treatment of said “oral mucositis,” not preventing said “oral mucositis” in the absolute meaning of “prevention,” as noted above. In this respect, no guidance is presented as to how one determines what cells are expected to experience said “oral mucositis.” This is particularly important regarding the term “prevention” since it is not within the skill of the ordinary artisan to accurately predict which cells will have experience said toxicity. Thus, in the absence of such guidance in the specification, the ordinary artisan would not know how to identify cells that may experience said “oral mucositis.”
(8) Quantity of Experimentation Required to Make and Use the Invention
In view of the factors discussed above, the state of the art with regard to preventing said “oral mucositis” in general is fairly complex and sufficiently unpredictable such that the skilled artisan would have been required to undertake undue experimentation to determine the exact conditions and manner and/or process of execution to arrive at those conditions amenable to actually preventing said “oral mucositis” in the absence of detailed guidance to this effect. Absent such direction or guidance as to how the skilled artisan would go about preventing said “oral mucositis,” one of ordinary skill in the art would have no alternative recourse but to undertake an exhaustive, and, thus, unduly burdensome search of methods to practice the claimed invention.
Subsequent claims 2-6, 8-11 and 13 depend on claim 1, and are thus, not enabled on this basis as well.
Claim Rejections – 35 U.S.C. § 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.
Claims 1-6, 8-11, 13 and 15-21 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by ROSENBLUH (US 2015/0064291 A1, Publ. Mar. 5, 2015; US equivalent of WO 2013/136270 A, on 06/02/2023 IDS; hereinafter, “Rosenbluh”).
Rosenbluh is directed to
NOVEL METHODS AND COMPOSITIONS FOR TREATMENT OF DISEASE
ABSTRACT
An aspect of embodiments of the invention relates to providing novel therapeutic compositions comprising herbal extracts of the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica. The compositions exhibit increased therapeutic activity for treatment of various inflammatory diseases, in particular, inflammatory diseases of mucosa or skin relative to previously identified compositions. In addition the compositions exhibit increased solubility relative to previously identified compositions. In an embodiment of the invention, the ratio of Sambucus nigra:Echinacea purpurea: Centella asiatica is 7:1:2. An embodiment of the invention provides methods for preparing an aqueous therapeutic composition comprising extracts of the aforementioned plant species, using at least two extractions.
Rosenbluh, title & abstract. In this regard, Rosenbluh exemplifies “Extract N” obtained from extracts of Sambucus nigra, Echinacea purpurea, and Centella asiatica at a “ratio of 70:10:20 by weight”:
Example 1b
Synthesis of Extract N
[0036] Synthetic scheme 100 described in example 1a was followed with the following details, in accordance with an embodiment of the invention.
[0037] Sambucus nigra (flowering tops) was mixed with 70% ethanol (8:1 solvent to plant ratio) according to block 10. Upon removing insoluble plant matter and drying solvent according to block 12, 3.29 kg of dried Sambucus nigra extract were formed.
[0038] Echinacea purpurea (rhizome and roots) was mixed with 70% ethanol (8:1 solvent to plant ratio) according to block 20. Upon removing insoluble plant matter and drying solvent according to block 22, 470 g (grams) of dried Echinacea purpurea extract were formed.
[0039] Centella asiatica (aerial parts) was contacted with 70% ethanol (8:1 solvent to plant ratio) according to block 30. Upon removing insoluble plant matter and drying solvent according to block 32, 940 g of dried Centella asiatica extract were formed.
[0040] The three dried extracts from the three herbs (ratio of 70:10:20 by weight) were combined in accordance with block 40. In accordance with block 42, 47 L of water were added and the mixture was stirred for 12 hours. 113.9 L of 96% ethanol was added to the mixture to form 160.9 L of a 70% ethanol alcoholic mixture according to block 44. The mixture was filtered in accordance with block 46 and the insoluble material was removed. Ethanol was evaporated in accordance with block 48 and the solution was spray-dried according to block 50 to form 3.2 kg of a dry herbal powder, designated as Extract N. The yield of this process (percentage by weight relative to dried extracts added according to block 40) was 68.7%.
(Rosenbluh, par. [0036]-[0040], Ex 1b), which is formulated into a “mouth rinse”:
Example 6a
Pharmaceutical Compositions Comprising Extracts
According to Embodiments of the Invention
[0084] 2.601 kg of Extract N was stirred for 12 hours with 10.379 kg of PG and 26.01 g sucralose to form a concentrate solution. 2.5 g of concentrate solution was mixed with 47.5 ml of saline solution to prepare a mouth rinse.
[…]
(Rosenbluh, par. [0084], Ex 6a) that is administered to patients receiving radiotherapy of 50-70 Gy concurrently with cisplatin chemotherapy in a dose of either 60-100 mg/m2 (milligrams per square meter), administered once every 21 days, or 30-40 mg/m2, administered once a week:
Example 7a
Methods of Treatment Using Compositions
According to Embodiments of the Invention
[0087] OM is among the most frequently reported and potentially most debilitating condition associated with cancer chemotherapy and radiation treatment, ranging in incidence from 10%-75% in patients receiving chemotherapy or radiotherapy, 70-90% in bone marrow transplant recipients and >95% of patients receiving combination radiation and chemotherapy for head and neck cancers (HNC). OM has been associated with increased analgesic and antibiotic use, febrile days, need for gastric tube or parenteral nutrition, length of hospital stay, unplanned and emergency room visits and total medical expenses, all of which have a negative impact on health and economic outcomes. Approximately 500,000 patients develop OM in the United States annually, and it is considered largely unpreventable.
[0088] A double blind, randomized, placebo controlled, fixed-dose, comparative study testing effects of mouth rinse according to example 6a in OM is performed in patients undergoing CRT (chemo-radio therapy) for HNC. Patients are randomized to receive either active mouth rinse or a placebo according to a 1:1 randomization schedule. Rinse dose is 15 ml of 1% oral rinse, as described in example 6, at a frequency of three times daily. The placebo is prepared using PG, sucralose and food coloring, diluted in saline.
[0089] About 104 subjects receive treatment for approximately 7-9 weeks, concurrently with CRT and extended until resolution of severe mucositis. Subjects are scheduled to receive a continuous course of external beam irradiation delivered either through intensity modulated radiotherapy or 3D planning. The cumulative prescription dose is between 50-70 Gy. A minimum of 25% of the oral cavity receives a dose of 50 Gy or more. Radiotherapy is delivered concurrently with cisplatin chemotherapy in a dose of either 60-100 mg/m2 (milligrams per square meter), administered once every 21 days, or 30-40 mg/m2, administered once a week.
(Rosenbluh, par. [0087]-[0089], Ex 7a; see also Rosenbluh, Ex. 4, noting “OM” as “Oral Mucositis” above par. [0069]).
Regarding independent claims
1. ([…]) A method for prevention and/or treatment of oral mucositis in a patient in need thereof, wherein the patient is treated with a once-weekly regimen of 30-40 mg/m2 of cisplatin, comprising, administering to the patient, a composition comprising extracts from the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica.
[…]
15. ([…]) A method for treatment of pain associated with oral mucositis in a patient in need thereof, wherein the patient is treated with cisplatin, comprising, administering to the patient, a composition comprising extracts from the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica.
Rosenbluh clearly teaches “Extract N” obtained from extracts of Sambucus nigra, Echinacea purpurea, and Centella asiatica at a “ratio of 70:10:20 by weight” (Rosenbluh, par. [0036]-[0040], Ex 1b), formulated into a “mouth rinse” (Rosenbluh, par. [0084], Ex 6a) that is administered to patients receiving radiotherapy concurrently with cisplatin chemotherapy (Rosenbluh, par. [0087]-[0089], Ex 7a), WHEREBY it is noted:
a “mouth rinse” (Rosenbluh, par. [0084], Ex 6a) containing “Extract N” obtained from extracts of Sambucus nigra, Echinacea purpurea, and Centella asiatica at a “ratio of 70:10:20 by weight” (Rosenbluh, par. [0036]-[0040], Ex 1b) reads on a “composition comprising extracts from the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica” of claims 1 and 15;
“OM,” i.e., “Oral Mucusitis” (Rosenbluh, par. [0087], Ex 7a, noting “OM” is “the most frequently reported and potentially most debilitating condition associated with cancer chemotherapy and radiation treatment, ranging in incidence from 10%-75% in patients receiving chemotherapy or radiotherapy, 70-90% in bone marrow transplant recipients and >95% of patients receiving combination radiation and chemotherapy for head and neck cancers (HNC)”), in patients receiving radiotherapy of 50-70 Gy concurrently with cisplatin chemotherapy in a dose of either 60-100 mg/m2 (milligrams per square meter), administered once every 21 days, or 30-40 mg/m2, administered once a week (Rosenbluh, par. [0089], Ex 7a), reads on the instant patient populations for:
“oral mucositis” when “the patient is treated with a once-weekly regimen of 30-40 mg/m2 of cisplatin” of claim 1 (see MPEP § 2131.03 regarding prior art anticipating claimed numerical ranges), and
“pain associated with oral mucositis in a patient in need thereof, wherein the patient is treated with cisplatin” of claim 15; and
“testing effects of mouth rinse according to example 6a in OM is performed in patients undergoing CRT (chemo-radio therapy) for HNC” with a “Rinse dose [that] is 15 ml of 1% oral rinse, as described in example 6, at a frequency of three times daily” (Rosenbluh, par. [0088], Ex 7a) reads on the active step of claims 1 and 15 for “administering to the patient.”
Thus, Rosenbluth anticipates claims 1 and 15.
Regarding claims 2-4, 16 and 18-19 and the requirements:
2. ([…]) The method according to claim 1 wherein the composition is in the form of an oral rinse.
3. ([…]) The method according to claim 2 wherein the herbal extracts are extracts produced by a first hydroalcoholic extraction from plant matter, followed by a second hydroalcoholic extraction of the first extract.
4. ([…]) The method according to claim 1 wherein the ratio of Sambucus nigra: Echinacea purpurea: Centella asiatica extracts in the combination is 7:1:2.
[…]
16. ([…]) The method according to claim 15 wherein the composition is in the form of an oral rinse.
[…]
18. ([…]) The method according to claim 15 wherein the herbal extracts are extracts produced by a first hydroalcoholic extraction from plant matter, followed by a second hydroalcoholic extraction of the first extract.
19. ([…]) The method according to claim 15 wherein the ratio of Sambucus nigra:Echinacea purpurea:Centella asiatica extracts in the combination is 7:1:2.
Rosenbluth teaches:
a “mouth rinse” (Rosenbluh, par. [0084], Ex 6a) containing “Extract N” obtained from extracts of Sambucus nigra, Echinacea purpurea, and Centella asiatica at a “ratio of 70:10:20 by weight” (Rosenbluh, par. [0036]-[0040], Ex 1b), which reads on an “oral rinse” of claims 2 and 16;
wherein “Extract N” (Rosenbluh, par. [0036]-[0040], Ex 1b) is obtained by 70% ethanol extraction of the respective plant materials (Rosenbluh, par. [0037]-[0039], Ex 1b) followed by a extraction from a 70% ethanol alcoholic mixture (Rosenbluh, par. [0040], Ex 1b), thereby reading on “wherein the herbal extracts are extracts produced by a first hydroalcoholic extraction from plant matter, followed by a second hydroalcoholic extraction of the first extract” of claims 3 and 18; and
“Extract N” obtained from extracts of Sambucus nigra, Echinacea purpurea, and Centella asiatica at a “ratio of 70:10:20 by weight” (Rosenbluh, par. [0036]-[0040], Ex 1b), which reads on “wherein the ratio of Sambucus nigra: Echinacea purpurea: Centella asiatica extracts in the combination is 7:1:2” of claims 4 and 19 (see MPEP § 2131.03 regarding prior art anticipating claimed numerical ranges).
Thus, Rosenbluth anticipates claims 2-4, 16 and 18-19.
Regarding claims 5-6, 17 and 20-21 and the requirements:
5. ([…]) The method according to claim 1 wherein the patient is undergoing radiotherapy.
6. ([…]) The method according to claim 5 wherein the cumulative dose of radiation is up to 65 Gy.
[…]
17. ([…]) The method, according to claim 15, wherein the patient is treated with a once-weekly regimen of 30-40 mg/m2 of cisplatin.
[…]
20. ([…]) The method according to claim 15 wherein the patient is undergoing radiotherapy.
21. ([…]) The method according to claim 20 wherein the cumulative dose of radiation is up to 65 Gy.
Rosenbluh teaches patients receiving radiotherapy of 50-70 Gy concurrently with cisplatin chemotherapy in a dose of either 60-100 mg/m2 (milligrams per square meter), administered once every 21 days, or 30-40 mg/m2, administered once a week. Rosenbluh, par. [0089], Ex 7a. See MPEP § 2131.03 regarding prior art anticipating claimed numerical ranges.
Thus, Rosenbluth anticipates claims 5-6, 17 and 20-21.
Regarding claims 8-11 and the requirements:
8. ([…]) The method according to claim 1 wherein the herbal extract is present in an amount of 1% of the composition.
9. ([…]) The method according to claim 2 wherein the oral rinse is administered in an amount of 15 ml per administration.
10. ([…]) The method according to claim 9 wherein the oral rinse is administered between 1 and 5 times per day.
11. ([…]) The method according to claim 10 wherein the oral rinse is administered 3 times per day.
Rosenbluth teaches that “[r]inse dose is 15 ml of 1% oral rinse, as described in example 6, at a frequency of three times daily” (Rosenbluh, par. [0088]; referring to Rosenbluh, par. [0084], Ex 6a), which reads on
“wherein the herbal extract is present in an amount of 1% of the composition” of claim 8,
“wherein the oral rinse is administered in an amount of 15 ml per administration” of claim 9, and
wherein the oral rinse is administered “between 1 and 5 times per day” of claim 10, and “3 times per day” of claim 11.
See MPEP § 2131.03 regarding prior art anticipating claimed numerical ranges.
Thus, Rosenbluth anticipates claims 8-11.
Regarding claim 13 and the requirements:
3. ([…]) The method according to claim 1 wherein the patient suffers from head/neck cancer.
Rosenbluh teaches “OM” is “the most frequently reported and potentially most debilitating condition associated with cancer chemotherapy and radiation treatment, ranging in incidence from 10%-75% in patients receiving chemotherapy or radiotherapy, 70-90% in bone marrow transplant recipients and >95% of patients receiving combination radiation and chemotherapy for head and neck cancers (HNC)” (Rosenbluh, par. [0087], Ex 7a), which reads on “wherein the patient suffers from head/neck cancer”
Thus, Rosenbluth anticipates claim 13.
Claim Rejections – 35 U.S.C. § 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. § 103(a) 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 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. § 102(b)(2)(C) for any potential 35 U.S.C. § 102(a)(2) prior art against the later invention.
Claims 1-6, 8-11, 13, 15-21, 28 and 30 are rejected under 35 U.S.C. § 103 as being unpatentable over ROSENBLUH (US 2015/0064291 A1, Publ. Mar. 5, 2015; US equivalent of WO 2013/136270 A, on 06/02/2023 IDS; hereinafter, “Rosenbluh”), in view of ELTING (Elting,L.S., et al., Patient-reported Measurements of Oral Mucositis in Head and Neck Cancer Patients Treated With Radiotherapy With or Without Chemotherapy, Cancer, 10 (Nov. 15, 2008) pp 2704-2713; hereinafter, “Elting”).
The teachings of Rosenbluh, as set forth in the above rejection of claims 1-6, 8-11, 13 and 15-21 under 35 U.S.C. § 102 (a)(1) are hereby incorporated. However, Rosenbluh DOES NOT EXPRESSLY TEACH the instant requirements of claims 28 and 30 for an “MTS score of 1 or higher during the 24 hours preceding administration of the cisplatin” and “pain associated with oral surgery”:
28. ([…]) The method according to claim 15 wherein the patient suffers from pain associated with oral mucositis as determined by an MTS score of 1 or higher during the 24 hours preceding administration of the cisplatin.
[…]
30. ([…]) A method for treatment of pain associated with oral surgery in a patient in need thereof, wherein the patient is treated with cisplatin, comprising, administering to the patient, a composition comprising extracts from the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica.
Based on the state of the art, an artisan of ordinary skill would have found each of these features obvious.
Elting, for instance, is directed to:
Patient-reported measurements of oral mucositis in head and neck cancer patients treated with radiotherapy with or without chemotherapy: demonstration of increased frequency, severity, resistance to palliation, and impact on quality of life
Abstract
Background: The risk, severity, and patient-reported outcomes of radiation-induced mucositis among head and neck cancer patients were prospectively estimated.
Methods: A validated, patient-reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales were used to measure mucositis (reported as mouth and throat soreness), daily functioning, and use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT.
Results: Contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3-4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3-4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity. The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at Week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of 1 or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6.
Conclusions: Mucositis occurs among virtually all patients who are undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed.
Elting, title & abstract. In this regard, Elting describes “patient-reported mouth and throat soreness (MTS)” (Elting, p. 2705, par. 5, cont. on p. 2706), which is defined as:
Definitions
Mucositis was measured on the basis of patient-reported MTS, defined as any positive response to Question 2 of the previously validated OMDQ (Fig. 1). MTS was measured on a scale of 0 (no soreness) to 4 (extreme soreness;). By using the same tool, Stiff et al found that bone marrow transplant patients’ MTS scores were comparable to clinicians’ assessments of oral mucositis, a finding which supports our use of this endpoint.8
(Elting, p. 2706, par. 1), wherein “MOUTH AND THROAT SORENESS” is scored as 0 for “No soreness,” 1 for “A little soreness,” 2 for “Moderate soreness,” 3 for “Quite a lot of soreness,” and 4 for “Extreme soreness” (Elting, p. 2707, Fig. 1). Elting also reports that “Fifty-six percent of oral cavity and/or oropharynx and 44% of larynx and/or hypopharynx patients reported MTS >0 at baseline, presumably resulting from either previous surgery or tumor”:
Distributions of mean age, sex, and race of the oral cavity and/or oropharynx and larynx and/or hypopharynx groups were similar (Table 2). There were differences in concomitant chemotherapy (66% vs 48%; P = .02) and intensity-modulated radiation therapy rates (71% vs 29%; P < .001) between the oral cavity and/or oropharynx and larynx and/or hypopharynx groups, respectively, because of different standards of care. Patients in the larynx and/or hypopharynx group had significantly lower stages of disease than their counterparts with oral cavity and/or oropharynx cancers (P < .001; Table 2). Small differences in baseline Eastern Cooperative Oncology Group (ECOG) status reflected the expected clinical presentations of the 2 populations. However, the mean FACT-G, ECS, and FACIT-fatigue scores at baseline were virtually identical and were similar to those previously reported for head and neck cancer patients (FACT-G head and neck normative reference value = 73.1; standard deviation [SD] = 17.8).17,18 Fifty-six percent of oral cavity and/or oropharynx and 44% of larynx and/or hypopharynx patients reported MTS >0 at baseline, presumably resulting from either previous surgery or tumor. Mean RT doses (oral cavity and/or oropharynx = 66 Gy; range, 48 Gy to 74 Gy vs larynx and/or hypopharynx = 68 Gy; range, 60 Gy to 72 Gy) and duration (47 days, both groups) were the same for both groups. Median RT doses also were the same (oral cavity and/or oropharynx = 69 Gy vs larynx and/or hypopharynx = 70 Gy).
(Elting, p. 2706, par. 7, cont. through p. 2708), which encompasses an “MTS score of 1 or higher during the 24 hours preceding administration of the cisplatin” of claim 28, and the patient population for “pain associated with oral surgery” of claim 30.
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to follow Rosenbluh’s treatment regimen with “Extract N” (Rosenbluh, par. [0036]-[0040], Ex 1b) as a “mouth rinse” (Rosenbluh, par. [0084], Ex 6a) for OM in patients receiving radiotherapy concurrently with cisplatin chemotherapy (Rosenbluh, par. [0087]-[0089], Ex 7a) for “Fifty-six percent of oral cavity and/or oropharynx and 44% of larynx and/or hypopharynx patients reported MTS >0 at baseline, presumably resulting from either previous surgery or tumor” per Elting (Elting, p. 2706, par. 7, cont. through p. 2708). One would have been motivated to do so with a reasonable expectation of success since both Rosenbluh and Elting are concerned with similar problems in the art, namely the treatment or oral mucositis with radiotherapy with or without chemotherapy. Rosenbluh, abstract; Elting, abstract. Further, it is well within the skill of the ordinary artisan to select suitable scoring and treatment polulation associsted with oral mucositis. Doing so amounts to no more than combining prior art elements according to known methods to yield predictable results.
Thus, the prior art renders claims 28 and 30 obvious.
Conclusion
Claims 1-6, 8-11, 13, 15-21, 28 and 30 are rejected. No claims are allowed.
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/DOMINIC LAZARO/Primary Examiner, Art Unit 1611