DETAILED ACTION
Status of Claims
The amendments, and arguments, filed April 21, 2026, are acknowledged and have been fully considered. Claims 1-6, 8-11, 13, 28 and 30 are pending and currently under consideration. Claims and 28 have been amended; claims 15-21 have been cancelled; and claims 7, 12, 14, 22-27 and 29 were previously cancelled. 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: Final
Withdrawn Claim Objections & Rejections
The objections to claims 1 and 28 (items A. and B. at par. 1-2 of the 10/22/2025 Office action) are withdrawn in light of applicant’s 04/21/2026 amendments. Applicant’s 04/21/2026 remarks at p. 4, par. 2, are acknowledged.
The rejection of claims 1-6, 8-11 and 13 under 35 U.S.C. § 112 (a) or 35 U.S.C. § 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for not being enabling (at par. 3-14 of the 10/22/2025 Office action), is withdrawn in light of applicant’s 04/21/2026 amendments. Applicant’s 04/21/2026 remarks at p. 4, par. 3, are acknowledged.
The rejection of claims 1-6, 8-11, 13 and 15-21 under 35 U.S.C. § 102 (a)(1); 35 U.S.C. § 103 (a)] by ROSENBLUH (US 2015/0064291 A1) (at par. 15-26 of the 10/22/2025 Office action), is maintained in modified form, in light of applicant’s 04/21/2026 amendments, which cancel claims 15-21.
The rejection of claims 1-6, 8-11, 13, 15-21, 28 and 30 under 35 U.S.C. § 103 over ROSENBLUH, in view of ELTING (Cancer, 10 (Nov. 15, 2008) pp 2704-2713) (at par. 27-31 of the 10/22/2025 Office action), is maintained in modified form, in light of applicant’s 04/21/2026 amendments, which cancel claims 15-21.
Modified Claim Rejections – 35 U.S.C. § 102 – Necessitated by Amendments
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 and 13 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”; of record).
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.
[0090] Safety is evaluated by general toxicity based on vital signs and physical examinations. Efficacy is evaluated by proportion of patients in active treatment group versus placebo group scoring a 3-4 according to WHO (World Health Organization) oral toxicity scale for OM at a cumulative radiation dosage of 50 Gy.
[0091] WHO oral toxicity scale for OM is as follows: Grade 0: No mucositis or mucosal lesions. Grade 1: erythema, mucosal sensitivity and pain. Grade 2: Ulceration, ability to eat solid foods. Grade 3: Ulceration, oral intake limited to fluids. Grade 4: Ulceration, oral feeding is impossible.
[0092] In an open-labeled section of the trial, seven patients were treated with the pharmaceutical composition described in Example 6a. A graph showing OM score relative to cumulative radiation dose is shown in FIG. 4. Patients 5 and 6 had overlapping scores during the course of treatment and are represented by one line.
[0093] In the patient population tested, approximately 75% of patients who receive equivalent cumulative doses of radiation to the oral cavity are expected, based on historical data, to develop grade 3-4 OM. One of the patients dropped out of the trial after a very short duration of treatment due to an apparent allergic reaction to one of the components in the composition. Out of the remaining 6 patients, 4 were considered to have responded favorably to treatment, as the scoring in these patients did not exceed 1 throughout the treatment. One additional patient was considered a partial responder as the patient's development of OM was delayed until after the patient received a cumulative dose of>40 Gy of radiation.
[0094] The results of the open-label section of the trial show that compositions prepared according to embodiments of the invention are effective in treating patients at risk of developing OM, including patients who have received radiation to the oral cavity. Similar results are expected from the complete trial.
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(Rosenbluh, par. [0087]-[0094], Ex 7a & Fig. 4; see also Rosenbluh, Ex. 4, noting “OM” as “Oral Mucositis” above par. [0069]).
Regarding independent claims
1. ([…]) A method for treatment of oral mucositis in a patient in need thereof suffering from oral micositis pain, 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, thereby reducing pain in the patient.
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 claim 1;
“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 to 40 mg/m2 of cisplatin” of claim 1 (see MPEP § 2131.03 regarding prior art anticipating claimed numerical ranges); 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) for “treating patients at risk of developing OM, including patients who have received radiation to the oral cavity” (Rosenbluh, par. [0094]) with efficacy, wherein “[4 out of 6 patients] were considered to have responded favorably to treatment, as the scoring in these patients did not exceed 1 throughout the treatment” (Rosenbluh, par. [0093], Fig. 4; “Grade 0: No mucositis or mucosal lesions,” and “Grade 1: erythema, mucosal sensitivity and pain,” Rosenbluh, par. [0091]), thereby reading on the active step of claim 1 for “administering to the patient [‘in need thereof suffering from oral micositis pain’]” for “reducing pain in the patient” .
Thus, Rosenbluth anticipates claim 1.
Regarding claims 2-4 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.
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 claim 2;
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 claim 3; 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 claim 4 (see MPEP § 2131.03 regarding prior art anticipating claimed numerical ranges).
Thus, Rosenbluth anticipates claims 2-4.
Regarding claims 5-6 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.
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.
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.
Response to Arguments
Applicants’ arguments, filed on April 21, 2026 (hereinafter, referred to as “Remarks”), have been fully considered, but they are not persuasive.
Applicant argues:
With respect to claim 1 and claims which depend therefrom, applicant respectfully disagrees, noting the amendment made to claim 1, and making reference to paragraph [0089] which reads, “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 does not suggest that there is a difference in outcome or effect in treatment of oral mucositis between any of the possible dosages of cisplatin, nor does Rosenbluh indicate that in specific dosages of cisplatin, patients suffering from oral mucositis pain can find relief using compositions comprising extracts from the plant species Sambucus nigra, Echinacea purpurea, and Centella asiatica.
The inventors in the instant application have surprising found that the composition described in claim 1 works best for treatment of oral mucositis in a specific patient population, and is actually effective in reducing pain in patients exhibiting pain at baseline. See page 8, lines 16-19 of the application as filed, “It is suggested that Composition 1 works best when used to prevent OM during low intensity chemotherapy, as shown by the decrease in maximum observed score in the Q1W Composition 1 treatment group, relative to the placebo group, especially in those having pain within the past 24 hours, when compared to the high Q3W group.” See also page 9, lines 8-10 which read, “Composition 1 appeared to: reduce the incidence of severe OM in patients who started the once-weekly cisplatin regimen with pre-existing mouth pain, and (2) lower the overall level of patient-reported mouth and throat soreness (AUC), as measured recorded daily during CRT.”
This distinction between chemotherapy treatment groups and effect of composition 1 on pain as claimed could not have been anticipated by a reading of Rosenbluh alone.
Remarks, p. 4, par. 5 to p. 5, par. 2.
In response: the scope of the patient population in independent claim 1 is drawn to “wherein the patient is treated with a once-weekly regimen of 30 to 40 mg/m2 of cisplatin” with no further limitations, such as “low intensity chemotherapy” relating to the Q1W group in the instant specification, as argued by applicant. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In this respect, Rosenbluh shows the treatment of oral mucositis (OM) 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), wherein the latter reads on the claimed patient population per the broadest reasonable interpretation of the claims, absent any further limitations on the patient population, for instance, limitations excluding concurrent radiotherapy as would appear to be shown in the Q1W vs Q3W study discussed in the instant published application, US 2023/0390350 A1, at par. [0023]-[0038].
Modified Claim Rejections – 35 U.S.C. § 103 – Necessitated by Amendments
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, 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 and 13 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 1 wherein the patient suffers from pain associated with oral mucositis as determined by a Mouth and Throat Soreness (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 rradiotherapy 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 population associated 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.
Response to Arguments
Applicants’ arguments, filed on April 21, 2026 (hereinafter, referred to as “Remarks”), have been fully considered, but they are not persuasive.
Applicant argues:
The applicant respectfully disagrees. Reference is made to Elting on page 2708, bottom of 2nd column, which reads, “Use of chemotherapy did not significantly increase the risk of severe mucositis. Among patients with oral cavity and/or oropharynx tumors, 88% of those who received chemotherapy developed grade 3-4 MTS compared with 85% of those who did not receive chemotherapy (P=.93).” A careful reading of Elting indicates there is no difference with regard to the incidence of OM whether chemotherapy is used or not and what dose of chemotherapy is used. Contrary to Elting, the inventors in the instant application have found that specific chemotherapy patients receiving a once weekly cisplatin treatment, and experiencing pain at the time of treatment can indeed improve pain in oral mucositis. This distinction between chemotherapy treatment groups and effect of composition 1 on pain as claimed could not have been anticipated by Rosenbluh or Elting alone or in combination.
Furthermore, Elting stresses the lack of effectiveness of standard, state of the art treatments on pain in OM patients. See lower 2nd column on page 2711 to top of column 1 page 2712 which reports, “Consistent with previous reports, virtually all patients (96%) with grade 3-4 MTS used analgesics during RT. By the time MTS scores peaked at Weeks 5-6, greater than 60% of patients were regularly using analgesics, and almost 90% required analgesics at least 1 day per week. More than half of study subjects were using pain medication at Week 10. The majority of patients with grade 1-2 MTS were treated with nonsteroidal anti-inflammatory agents, however, greater than 70% of patients with MTS>3 required opioids. Considering the severity of patient-reported MTS, the frequency of analgesic use was not surprising. However, the persistence of high MTS scores despite the use of narcotics is a startling finding. Clearly, effective pain control was not achieved.” Despite effective pain control being difficult to attain in OM patients as clearly described by Elting, surprisingly, composition 1, was found by the inventors to effect pain relief, without adverse events which can be associated with opioid use, as illustrated in Example 3 and as claimed in instant claim 1 of the application.
Remarks, p. 5, par. 4-5, cont. on p. 6.
In response: it would be obvious 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 rradiotherapy 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 population associated with oral mucositis. Doing so amounts to no more than combining prior art elements according to known methods to yield predictable results.
Summary/Conclusion
Claims 1-6, 8-11, 13, 28 and 30 are rejected. No claims are allowed.
Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee 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 date of this final action.
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/DOMINIC LAZARO/Primary Examiner, Art Unit 1611
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