DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Current Status
This action is responsive to the amended claims of 06/25/2026. Claims 1-11 are pending. Claim 11 is new. Claims 1-11 have been examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date remains 07/06/2022.
Response to Arguments
Examiner acknowledges receipt of and has reviewed the amendments and remarks of 06/25/2026; no new matter is found.
The objections to claims 1-9 are withdrawn; the typo has been removed.
The 101 rejection to claims 2-9 is withdrawn; all pending claims are recast as method claims.
The 101 rejection of claims 1-10 is withdrawn; since all pending claims are methods of treatment, the JE is integrated into a practical application.
The 112(a) rejection of claims 1-9 is withdrawn since the claims no longer recite “prevention” of tumors.
The 112(b) rejection of claims 2-9 over “use” is withdrawn since all claims are not recast as method claims.
The 112(b) rejection of claim 6 is withdrawn; the rejected limitations now have antecedent basis in the subject being treated.
The 112(b) rejection of claim 9 is withdrawn; the rejected limitation was struck.
The 112(b) rejection of claims 9 and 10 over “the unit dosage form” is withdrawn for claim 9 and modified below for claim 10 to account for the amendments. Claim 9 now recites “a unit dosage form”. Claim 10 now depends from claim 8 which does not recite a unit dosage form.
The 112(b) rejection of claims 9 and 10 over “preferably” is withdrawn; all instances of preferably have been struck.
The 112(d) rejection of claim 6 is withdrawn for the same reasons as the 112(b) rejection of claim 6.
The 112(d) rejection of claim 9 is withdrawn for the same reasons as the 112(b) rejection of claim 9.
The 102 rejection of claims 1-10 over HADLEY is withdrawn due to amendment. HADLEY does not teach the claimed method steps. New prior art rejections are applied below to account for the method steps introduced by the amendments.
The double patenting rejections over co-pending Application No. 18/262,969, 18/556,818, 18/577,127, 19/071,026, and Patent No. 9,884,036 are withdrawn – the reference is drawn to a different method/use.
The double patenting rejection over U.S. Patent No. 9,918,956 is modified below to account for the instant claims now being drawn to a method of treating.
The double patenting rejection over U.S. Patent No. 10,058,525 is withdrawn – the reference is drawn to a different method/use.
The anticipatory double patenting rejection of claims 1-9 over U.S. Patent No. 10,004,713 is withdrawn for claims 2-6 and is modified below for claims 1 and 7-9 to account for amendments to the instant claims. The obviousness-type double patenting rejection of claim 10 over U.S. Patent No. 10,004,713 is similarly modified below.
The double patenting rejection over U.S. Patent No. 10,265,289 is withdrawn – the reference is drawn to a different method/use.
The double patenting rejection over U.S. Patent No. 10,246,401 is modified below to account for the instant claims now being drawn to a method of treating.
The double patenting rejection over U.S. Patent No. 10,238,702 is modified below to account for the instant claims now being drawn to a method of treating.
The double patenting rejection over U.S. Patent No. 10,314,806 is modified below to account for the instant claims now being drawn to a method of treating.
The double patenting rejections over U.S. Patent No. 11,547,715 and 11,376,267 are withdrawn – the reference is drawn to a different method/use.
The double patenting rejection over U.S. Patent No. 11,596,598 is modified below to account for the instant claims now being drawn to a method of treating.
The double patenting rejections over U.S. Patent No. 11,135,160, 12,156,861, 11,628,199, 12,150,926, 12,178,792, 12,364,677, and 12,194,013 are withdrawn – the reference is drawn to a different method/use.
Response to Amendment – Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
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 8-10 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.
Claim 8 recites “the pharmaceutical preparation”. There is insufficient antecedent basis for this limitation. The parent claim 7, by the recent amendment, no longer recites “a pharmaceutical preparation”, only “the medicament”. Thus, it is unclear what pharmaceutical preparation claim 8 is attempting to further limit. The metes and bounds of the claim are undefined rendering the claim indefinite. Dependent claims 9-10 are similarly rejected since they do not rectify the issue.
Claim 10 recites “the unit dosage form”. There is insufficient antecedent basis for this limitation. Claim 10, by amendment, depends from claim 8 which does not recite “a unit dosage form”. Thus, it is unclear what unit dosage form claim 10 is attempting to further limit. The metes and bounds of the claim are undefined rendering the claim indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 8-10 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claims 8 and 10 recite limitations which are outside of the scope of the claim from which they depend (see ¶31-32). Thus, these claims do not properly further limit the claims from which they depend. Dependent claim 9 is similarly rejected since it does not rectify the issue.
Note: to overcome the above 112 rejections, Applicant may consider replacing “the pharmaceutical preparation” in claim 8 with “the medicament”. Further, claim 10 may be amended to recite “a unit dosage form” rather than “the unit dosage form”.
Claim Rejections - 35 USC § 102(a)(1)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 1-5 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by PANDOL (WO 2005/099721; cited IDS 01/08/2024).
PANDOL teaches a method of treating a disease in a subject comprising administering to the subject a polyphenolic compound which is chlorogenic acid (Pg. 93 claims 1 and 3-4) wherein the disease is diffuse large B-cell lymphoma (Pg. 94 claims 11-12). Further, a pharmaceutical composition comprises the polyphenolic compound and a pharmaceutically acceptable carrier/diluent (Pg. 52 ¶209) and is formulated to be compatible with the intended route of administration including oral and injection (Pg. 53 ¶211-213).
Claims 1-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ZHANG (CN 113425710; pub. 24 Sept. 2021; cited IDS 01/08/2024; machine translation attached & referenced below).
ZHANG teaches a drug for treatment of central nervous system tumors comprising chlorogenic acid (Pg. 82 claim 1) wherein the tumor is a lymphoma (Pg. 82 claim 2), a primary central nervous system lymphoma (Pg. 82 claim 3), B-cell non-Hodgkin lymphoma (Pg. 83 claim 4), or diffuse B-cell lymphoma (Pg. 83 claim 5) of the brain, eye, or spinal cord (Pg. 84 claim 6). The drug preparation further comprises pharmaceutically acceptable excipients and is in the form of an oral or injectable preparation (Pg. 84 claims 7-8). The drug comprises 0.5-5.5 mg of 1.1 to 3.3 mg of chlorogenic acid (Pg. 85 claim 9). ZHANG teaches an in vivo animal study of chlorogenic acid treatment for diffuse large B-cell lymphoma of the orbit (eye) (Pg. 61 ¶n0137). The test drugs comprise only chlorogenic acid as the active ingredient (Pg. 62 ¶n0140-141). Mouse models of diffuse large B-cell lymphoma were administered the test drugs (Pg. 75 ¶n0171); treatment with chlorogenic acid test drugs shows good therapeutic effects (Pg. 77 ¶n0176 & Pg. 79 ¶n0180), i.e., the lymphoma was treated.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by MAUST (WO 2021/247758; pub. 09 Dec. 2021).
MAUST teaches a method of treating cancer in a subject comprising administering a therapeutically effective amount of an anticancer agent comprising chlorogenic acid (Pg. 53 claim 21) wherein the cancer is lymphoma, brain cancer, or spinal cord tumor (Pg. 53 claim 24). The lymphoma is non-Hodgkin’s lymphoma (Pg. 9 ¶1).
Claim Rejections - 35 USC § 102(a)(2)
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)(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 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by MAUST (WO 2021/247758; effectively filed 02 June 2021 – international filing date).
MAUST teaches the instant claims are described in ¶41, above. No priority document is cited since the international filing date is used as the effectively filed date.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over PANDOL (WO 2005/099721; cited IDS 01/08/2024) as applied to claims 1-5 and 7-8 above, further in view of MAUST (WO 2021/247758; pub. 09 Dec. 2021; effectively filed 02 June 2021) and in view of MA (Ma, J. et al., Cancer Management and Research, 2019, 11, 10175-10185).
The instant claims are drawn to treating diffuse large B-cell lymphoma with chlorogenic acid (claims 1-5) wherein the lymphoma is in the brain, eye, or spinal cord (claim 6) and the chlorogenic acid is in an oral/injectable pharmaceutical composition comprising an excipient (claims 7-8) wherein a unit dosage form of the composition comprises 0.5-5.5 mg (claim 9) or 1.1-3.3 mg (claim 10) of chlorogenic acid.
Determining the Scope and Contents of the Prior Art:
PANDOL teaches the method of claims 1-5 and 7-8, ¶39 above. Further, PANDOL teaches an effective amount of the polyphenolic compound (i.e., chlorogenic acid) is an amount that treats or inhibits cancer/tumor growth compared to a control using methods known in the art – dosages can be determined by the artisan depending on severity of the disease, age and weight of the subject, and neoplastic conditions of the subject (Pg. 51 ¶204).
MAUST teaches treating cancer in a subject by administering chlorogenic acid and a 1,2,4-trioxane (Pg. 53 claim 21) wherein the cancer is lymphoma, brain cancer, or spinal cord tumor (Pg. 53 claim 24). The lymphoma is non-Hodgkin’s lymphoma (Pg. 9 ¶1). The preferred dosage range is 0.5-50 mg/kg based on the weight of the 1,2,4-trioxane (Pg. 51 claim 23). The ratio of the 1,2,4-trioxane and the chlorogenic acid is between 0.1 and 0.01 (Pg. 49 claim 6); e.g., 5-50 mg/kg chlorogenic acid.
MA teaches diffuse large B-cell lymphoma (DLBCL) can manifest in the brain, spinal cord, and eyes (Pg. 10181 Discussion). Prognosis for patients with CNS involvement (brain, spine, eyes) is poorer compared to patients without CNS involvement (Pg. 10183 Left col. last ¶).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
PANDOL does not teach the lymphoma is in the brain, eye, or spinal cord nor the dosages of instant claims 9-10.
MAUST does not teach the lymphoma is DLBCL.
MA does not teach the instant treatment.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of treatments useful for DLBCL and possesses the technical knowledge necessary to make adjustments to the dosing to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding brain, eye, and spinal cord involvement in DLBCL and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references PANDOL, in view of MAUST, and in view of MA.
Regarding claims 1-6, the artisan would be motivated to utilize the method of PANDOL to treat DLBCL found in the brain, eye, or spinal cord of a subject since MAUST teaches chlorogenic acid is utilized to treat brain or spinal cord tumors in addition to lymphoma (Pg. 53 claim 24) and since MA teaches DLBCL manifests in such parts of the CNS (Pg. 10181 Discussion). Further, since the prognosis is poorer for patients with DLBCL in the brain, eyes, or spinal cord, as recognized by MA (Pg. 10183 Left col. last ¶), the artisan would be motivated to find a treatment which works for such patients.
Regarding claims 7-10, the artisan would have been motivated to optimize the dosage of chlorogenic acid.
MPEP 2144.05(II)(A) provides guidance about the routine optimization of prior art conditions: "Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").”
Furthermore, MPEP 2144.05(I) provides guidance about overlapping ranges: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists…Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
In the instant case, MAUST teaches dosages of chlorogenic acid for lymphoma and CNS tumors (Pg. 51 claim 23; Pg. 49 claim 6). These dosages are considered to overlap with/approach the instantly claimed dosages. Since PANDOL teaches dosages can be determined by the artisan, using techniques known in the art, depending on severity of the disease, age and weight of the subject, and neoplastic conditions of the subject (Pg. 51 ¶204), the artisan would recognize the dosage of chlorogenic acid as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent any evidence demonstrating the contrary, the determination of the optimum or workable dosage of chlorogenic acid would have been well within the practice of the artisan given the guidance of the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 7-8 are provisionally rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claims 1, 4-6, 12, 14, and 17-18 of copending Application No. 17/053,037 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims are drawn to a method of treating brain tumors selected from anaplastic astrocytoma, oligodendrocytoma, and oligodendroblastoma by administering a pharmaceutical preparation comprising chlorogenic acid (ref. claims 5-6, 12, 14, and 17-18). The pharmaceutical preparation is an oral or injectable preparation (ref. claims 1 and 4). The reference brain tumors are species of the instant central nervous system tumor. Thus, the instant claims are anticipated by the reference claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 7-8 are rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,004,713. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims are drawn to a method of treating oligodendroglioma by administering a pharmaceutical preparation comprising chlorogenic acid and adjuvants/auxiliaries to a patient (ref. claims 1-4); the preparation is oral or an injection (ref. claim 5). Oligodendroglioma is a species of the instant central nervous system tumor, thus the instant claims are anticipated.
Claims 1 and 7-10 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,004,713 in view of ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53; provided 03/25/2026).
The instant claims are drawn to the method of claims 1 and 7-8 wherein the dosage of chlorogenic acid is 0.5-5.5 mg or 1.1-3.3 mg.
Determining the Scope and Contents of the Prior Art:
The reference claims teach the method of instant claims 1 and 7-8 (¶51). Further, the preparation comprises 1-3000 mg of chlorogenic acid per unit (ref. claim 2) and the dosage is 10-40 mg/kg (ref. claims 3-4).
ANSEL teaches the safe and effective dose of a drug depends on a number of factors including characteristics of the drug, the dosage form, and a variety of patient factors (Pg. 48 Left Col. para 2) and the effective dose may be different for different patients (Pg. 48 Left Col. para 4).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
U.S. Patent No. 10,004,713 does not teach the unit dosage form contains 0.5-5.5 mg or 1.1-3.3 mg of the chlorogenic acid.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a unit dosage form of chlorogenic acid useful for treatment of a CNS tumor and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize/enhance the dosage. Said artisan has also reviewed the problems in the art regarding optimization of dosages and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent No. 10,004,713 in view of ANSEL.
Regarding claims 9-10, the artisan would have been motivated to optimize the unit dosage amount of chlorogenic acid in the pharmaceutical preparation. See MPEP 2144.05(II)(A) and 2144.05(I) quotations above. In the instant case, U.S. Patent ‘713 teaches a unit dosage form contains 1-3000 mg (ref. claim 2) and dosage of 10-40 mg/kg (ref. claims 3-4). These dosages overlap with/approach the instantly claimed 0.5-5.5 mg and 1.1-3.3 mg. Since ANSEL teaches the safe and effective dose of a drug depends on various factors (Pg. 48 Left Col. para 2) and may be different for different patients (Pg. 48 Left Col. para 4), the artisan would recognize the dosage of chlorogenic acid as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent evidence demonstrating the contrary, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Claims 1 and 7-8 are rejected on the ground of anticipatory nonstatutory double patenting as being unpatentable over claims 1-2 and 9 of U.S. Patent No. 10,314,806. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims are drawn to a method of treating a brain glioma comprising administering to a subject a pharmaceutical preparation comprising chlorogenic acid (ref. claim 9); the preparation is oral or an injection (ref. claims 1-2). Since brain glioma is a species of the instant central nervous system tumor, the instant claims are anticipated.
Claims 1 and 7-10 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-2, 9, and 11-12 of U.S. Patent No. 10,314,806 in view of ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53; provided 03/25/2026).
The instant claims are drawn to the method of claims 1 and 7-8 wherein the dosage of chlorogenic acid is 0.5-5.5 mg or 1.1-3.3 mg.
Determining the Scope and Contents of the Prior Art:
The reference claims teach the method of instant claims 1 and 7-8 (¶53). Further, the dosage is 2-4 mg/kg (ref. claim 11) or 5-14 mg/kg per day (ref. claim 12).
ANSEL teaches the safe and effective dose of a drug depends on a number of factors including characteristics of the drug, the dosage form, and a variety of patient factors (Pg. 48 Left Col. para 2) and the effective dose may be different for different patients (Pg. 48 Left Col. para 4).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
U.S. Patent No. 10,314,806 does not teach the unit dosage form contains 0.5-5.5 mg or 1.1-3.3 mg of the chlorogenic acid.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a unit dosage form of chlorogenic acid useful for treatment of a CNS tumor and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize/enhance the dosage. Said artisan has also reviewed the problems in the art regarding optimization of dosages and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent No. 10,314,806 in view of ANSEL.
Regarding claims 9-10, the artisan would have been motivated to optimize the unit dosage amount of chlorogenic acid in the pharmaceutical preparation. See MPEP 2144.05(II)(A) and 2144.05(I) quotations above. In the instant case, U.S. Patent ‘806 teaches a dosage of 2-4 or 5-14 mg/kg (ref. claims 11-12). This dosage overlaps with/approaches the instantly claimed 0.5-5.5 mg and 1.1-3.3 mg. Since ANSEL the safe and effective dose of a drug depends on various factors (Pg. 48 Left Col. para 2) and may be different for different patients (Pg. 48 Left Col. para 4), the artisan would recognize the dosage of chlorogenic acid as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent evidence demonstrating the contrary, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Claims 1-10 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-5 and 10-14 of U.S. Patent No. 9,918,956 in view of PANDOL (WO 2005/099721; cited IDS 01/08/2024), further in view of MAUST (WO 2021/247758; pub. 09 Dec. 2021; effectively filed 02 June 2021) and further in view of MA (Ma, J. et al., Cancer Management and Research, 2019, 11, 10175-10185) as applied to claims 1-10 above.
The instant claims are drawn to a method of treating diffuse large B-cell lymphoma (DLBCL) (claims 1-5) in the brain, eye, or spinal cord (claim 6) by administering chlorogenic acid as a medicament comprising excipients (claim 7) in an oral/injectable form (claim 8). The dosage of chlorogenic acid is 0.5-5.5 mg or 1.1-3.3 mg (claim 9-10).
Determining the Scope and Contents of the Prior Art:
The reference claims are drawn to a chlorogenic acid powder comprising chlorogenic acid and supporting materials and various antioxidants (ref. claims 1-5 and 10-14). The disclosure of Patent No. 9,918,956 is referred to in order to understand the functionality of the claimed powder, in accordance with MPEP 804(II)(B)(1): “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).” The chlorogenic acid powder has good stability, good solubility, and safe application in clinic (Col. 17).
PANDOL, MAUST, and MA teach the method of claims 1-10 (see ¶48 above).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
U.S. Patent No. 9,918,956 does not teach the chlorogenic acid is administered to a subject to treat DLBCL.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods useful for treatment of DLBCL and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding chlorogenic treatments for DLBCL and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent No. 9,918,956 in view of PANDOL, in view of MAUST, and in view of MA.
Regarding claims 1-8, the artisan would be motivated to treat DLBCL by the method of PANDOL with the chlorogenic acid powder of the Patent No. ‘956 since the powder has good properties and is safe for clinical application (Col. 17). Further, since the combined prior art references PANDOL, MAUST, and MA teach treatment of brain, eye, and spinal cord DLBCL with chlorogenic acid (¶48), the artisan would have an expectation of success in using the Patent ‘956 powder for the treatment.
Regarding claims 9-10, the artisan would have been motivated to optimize the unit dosage amount of chlorogenic acid in the powder.
See MPEP 2144.05(II)(A) and 2144.05(I) quotations above. In the instant case, since PANDOL and MAUST teach dosages and motivation to optimize dosages (¶48), the artisan would recognize the dosage of chlorogenic acid as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent evidence demonstrating the contrary, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Claims 1-10 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,238,702 in view of PANDOL (WO 2005/099721; cited IDS 01/08/2024), further in view of MAUST (WO 2021/247758; pub. 09 Dec. 2021; effectively filed 02 June 2021) and further in view of MA (Ma, J. et al., Cancer Management and Research, 2019, 11, 10175-10185) as applied to claims 1-10 above.
The instant claims are drawn to a method of treating diffuse large B-cell lymphoma (DLBCL) (claims 1-5) in the brain, eye, or spinal cord (claim 6) by administering chlorogenic acid as a medicament comprising excipients (claim 7) in an oral/injectable form (claim 8). The dosage of chlorogenic acid is 0.5-5.5 mg or 1.1-3.3 mg (claim 9-10).
Determining the Scope and Contents of the Prior Art:
The reference claims are drawn to a pharmaceutical composition comprising chlorogenic acid and excipients (ref. claims 1-5) as an oral preparation (ref. claims 1 and 4). The disclosure of Patent No. 10,238,702 is referred to in order to understand the functionality of the claimed composition, in accordance with MPEP 804(II)(B)(1). The composition has clinical application (Col. 16) and chlorogenic acid has anticancer properties (Col. 1 Background ¶1).
PANDOL, MAUST, and MA teach the method of claims 1-10 (see ¶48 above).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
U.S. Patent No. 10,238,702 does not teach the chlorogenic acid is administered to treat DLBCL.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods useful for treatment of DLBCL and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding chlorogenic treatments for DLBCL and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent No. 10,238,702 in view of PANDOL, in view of MAUST, and in view of MA.
Regarding claims 1-8, the artisan would be motivated to treat DLBCL by the method of PANDOL with the pharmaceutical composition of the Patent No. ‘702 since the composition has clinical application (Col. 16) and chlorogenic acid has anticancer properties (Col. 1 Background ¶1).Further, since the combined prior art references PANDOL, MAUST, and MA teach treatment of brain, eye, and spinal cord DLBCL with chlorogenic acid (¶48), the artisan would have an expectation of success in using the Patent ‘702 composition for the treatment.
Regarding claims 9-10, the artisan would have been motivated to optimize the unit dosage amount of chlorogenic acid in the composition. See MPEP 2144.05(II)(A) and 2144.05(I) quotations above. In the instant case, since PANDOL and MAUST teach dosages and motivation to optimize dosages (¶48), the artisan would recognize the dosage of chlorogenic acid as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent evidence demonstrating the contrary, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Claims 1-10 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-2 and 11 of U.S. Patent No. 10,246,401 in view of PANDOL (WO 2005/099721; cited IDS 01/08/2024), further in view of MAUST (WO 2021/247758; pub. 09 Dec. 2021; effectively filed 02 June 2021) and further in view of MA (Ma, J. et al., Cancer Management and Research, 2019, 11, 10175-10185) as applied to claims 1-10 above.
The instant claims are drawn to a method of treating diffuse large B-cell lymphoma (DLBCL) (claims 1-5) in the brain, eye, or spinal cord (claim 6) by administering chlorogenic acid as a medicament comprising excipients (claim 7) in an oral/injectable form (claim 8). The dosage of chlorogenic acid is 0.5-5.5 mg or 1.1-3.3 mg (claim 9-10).
Determining the Scope and Contents of the Prior Art:
The reference claims are drawn to a crystalline form of chlorogenic acid (ref. claims 1-2 and 11). The disclosure of Patent No. 10,246,401 is referred to in order to understand the functionality of the claimed composition, in accordance with MPEP 804(II)(B)(1). The composition has good stability, meets requirements for active pharmaceutical ingredients, and improves product safety (Abstract).
PANDOL, MAUST, and MA teach the method of claims 1-10 (see ¶48 above).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
U.S. Patent No. 10,246,401 does not teach the chlorogenic acid is administered to treat DLBCL.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods useful for treatment of DLBCL and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding chlorogenic treatments for DLBCL and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent No. 10,246,401 in view of PANDOL, in view of MAUST, and in view of MA.
Regarding claims 1-8, the artisan would be motivated to treat DLBCL by the method of PANDOL with the crystalline form of the Patent No. ‘401 based on the advantageous properties disclosed in the abstract of ‘401. Further, since the combined prior art references PANDOL, MAUST, and MA teach treatment of brain, eye, and spinal cord DLBCL with chlorogenic acid and a pharmaceutical composition comprising the chlorogenic acid (¶48), the artisan would have an expectation of success in using the Patent ‘401 crystalline form in a composition for the treatment of DLBCL.
Regarding claims 9-10, the artisan would have been motivated to optimize the unit dosage amount of chlorogenic acid in the composition. See MPEP 2144.05(II)(A) and 2144.05(I) quotations above. In the instant case, since PANDOL and MAUST teach dosages and motivation to optimize dosages (¶48), the artisan would recognize the dosage of chlorogenic acid as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent evidence demonstrating the contrary, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Claims 1 and 7-10 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-4 and 6-9 of U.S. Patent No. 11,596,598 in view of MAUST (WO 2021/247758; pub. 09 Dec. 2021; effectively filed 02 June 2021) and in view of ANSEL (Ansel, H.C. et al. Pharmaceutical Dosage Forms and Drug Delivery Systems, Lippincott Williams & Wilkins, 7th ed., 1999, pages 48-53; provided 03/25/2026).
The instant claims are drawn to a method of treating central nervous system tumors (claim 1) by administering chlorogenic acid as a medicament comprising excipients (claim 7) as an injectable dosage form (claim 8). The dosage of chlorogenic acid is 0.5-5.5 mg or 1.1-3.3 mg (claim 9-10).
Determining the Scope and Contents of the Prior Art:
The reference claims are drawn to an anti-tumor composition comprising chlorogenic acid and excipients as a nasal powder (ref. claims 1-3) and injection thereof (ref. claim 4). The composition comprises 0.1-1 g of chlorogenic acid per 1 mL (ref. claim 3). The composition is directed for use in treatment of brain tumors glioblastoma, ependymoma, or oligodendrocytoma (ref. claims 6-9).
MAUST teaches treating brain cancer in a subject by administering chlorogenic acid (Pg. 53 claim 21 & 24).
ANSEL teaches the safe and effective dose of a drug depends on a number of factors including characteristics of the drug, the dosage form, and a variety of patient factors (Pg. 48 Left Col. para 2) and the effective dose may be different for different patients (Pg. 48 Left Col. para 4).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
U.S. Patent No. 11,596,598 does not teach a method of administering the chlorogenic acid to a subject.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods useful for treatment of brain tumors and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize/enhance the outcomes. Said artisan has also reviewed the problems in the art regarding chlorogenic acid treatments for brain tumor and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references U.S. Patent No. 11,596,598 in view of MAUST and in view of ANSEL.
Regarding claims 1 and 7-8, the artisan would be motivated to administer the pharmaceutical composition of the Patent No. ‘598 to a subject based on the method disclosed by MAUST. Since both Patent No. ‘598 and MAUST teach chlorogenic acid for treatment of brain tumor, the artisan would have an expectation of success.
Regarding claims 9-10, the artisan would have been motivated to optimize the unit dosage amount of chlorogenic acid in the composition. See MPEP 2144.05(II)(A) and 2144.05(I) quotations above. In the instant case, the reference claims teach the composition comprises 0.1-1 g of chlorogenic acid per 1 mL (ref. claim 3), these amounts approach the instant dosages depending on how much of the composition is administered by nasal aerosolization. Since ANSEL teaches effective dosages depend on a variety of patient and dosage form factors (see all teachings above), the artisan would recognize the dosage of chlorogenic acid as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent evidence demonstrating the contrary, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Conclusion
Claims 1-11 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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