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 .
Priority
The instant application 18/265,192 filed on June 2, 2023 is a 371 of PCT/EP2021/084252 filed on December 3, 2021, which claims priority to, and the benefits of Foreign Application No.
EP20211547.3 filed on December 3, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6/2/2023 and 10/2/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of Claims
Claims 1-13 are pending and under examination.
Specification
The disclosure is objected to because of the following informalities:
The disclosure contains an embedded hyperlink and/or other form of browser-executable code. For instance, on page 14, line 18 of the specification, said disclosure contains an embedded hyperlink. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
On page 14, line 21 of the specification: the recitation of “
PNG
media_image1.png
26
240
media_image1.png
Greyscale
” contains special character “□” and that appears to be a typographical error.
The use of the terms “[a]driamycin”, “BIO 3000, Baichanin A, Bonistein, Climagen F, Genivida, Prunetol, Differenol A”, which are trade name or mark used in commerce, has been noted in this application. Each of these terms should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claim 6 is objected to because of the following informalities:
Regarding claim 6, the claim language is missing a period (.) at the end of the sentence and that appears to be a typographical error.
Appropriate correction is required.
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.
Claim 6 is 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.
Regarding claim 6, the recitation of “wherein the genistein in the preparation comprises the structure:
PNG
media_image2.png
85
185
media_image2.png
Greyscale
” renders the claim indefinite. In the present case, the claimed term “genistein” is referring to “5,7-Dihydroxy-3-(4-hydroxyphenyl)chromen-4-one, 5,7-Dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one, 4',5,7-Trihydroxyisoflavone” according to page 6, line 16-20; and each of these chemical names is drawn to same compound having the structure of:
PNG
media_image3.png
200
316
media_image3.png
Greyscale
. However, when the compound (“genistein”) is used together with the transitional term "comprising", it is not clear what the compound is given that said transitional term
does not exclude additional and unrecited elements. See MPEP 2111.03, I with respect to transitional phrases “comprising”. In order to advance prosecution, the Examiner is examining claim 6 to the extent that genistein is a compound having the structure of:
PNG
media_image2.png
85
185
media_image2.png
Greyscale
.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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.
(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 1-6, 8, and 10-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yousefinejad et al. (Progress in Nutrition, 2019. Vol. 21, Supplement 1: 163-172; cited in the IDS filed on October 2, 2023), as evidenced by Lee et al. (Nephroiogy, 2011. Vol. 16: 30-38; cited in the IDS filed on October 2, 2023), Abbasnezhad et al. (Prev Nutr Food Sci. 2020. Vol. 25(2): 124-132), Serwer al. (J Vis Exp., 2010. Vol. 42: 1992) and PubChem (“Genistein | C15H10O5 | CID 5280961”; created on 9/16/2004).
Yousefinejad et al. teaches treatment with L-carnitine, genistein, or both in rats with nephrotic syndrome reduced the symptoms of nephrotic syndrome, as suggested by a lower level of urine protein (see e.g., p. 168, right column, line 8-11; Table 4). Please note the genistein taught by Yousefinejad et al. is a compound having the structure of:
PNG
media_image4.png
200
400
media_image4.png
Greyscale
, as evidenced by PubChem. Yousefinejad et al. further teaches in the controlled experimental study, the genistein group received daily 50 mg/kg body weight genistein by gavage, and 7.5 mg/kg body weight single dose Adriamycin® (an agent that induces nephrotic syndrome) through tail vein at the end of week 2 (see e.g., p. 164, right column, 1st-2nd paragraph under the “Animals and experimental diets” section). Please note Adriamycin® taught by Yousefinejad et al. is doxorubicin, as evidenced by Lee et al.; and the gavage taught by Yousefinejad et al. is an oral administration. Yousefinejad et al. further teaches the L-carnitine-genistein group receives 50 mg/kg body weight L-carnitine plus 50 mg/kg body weight genistein (see e.g., p. 164, right column, 2nd paragraph under the “Animals and experimental diets” section). Yousefinejad et al. further teaches for reaching this dosage, 15 mg genistein or L-carnitine was dissolved in 0.5 cc CMC (carboxymethyl cellulose dissolved in distilled water) (concentration: 0.5 mg/mL), which is a suspending agent for genistein, for reaching the final solution (concentration: 26 mg/mL) (see e.g., p. 164, right column, 2nd paragraph under the “Animals and experimental diets” section to p. 165, left column, line 2). Please note the CMC taught by Yousefinejad et al. is a pharmaceutically acceptable carrier.
Yousefinejad et al. clearly teaches the administration of 50 mg/kg body weight genistein as a single active agent by gavage to rat with Adriamycin®-induced nephrotic syndrome. It is noted that the Adriamycin® (doxorubicin) taught by Yosefinejad et al. is a well-known inducer of renal injury in rodents, which is a model of focal segmental glomerulosclerosis, as evidenced by Lee et al. (see e.g., p. 30, “Introduction” section); therefore, in view of the foregoing, the subject with Adriamycin®(doxorubicin)-induced nephrotic syndrome as taught by Yousefinejad et al. is a subject at risk of developing FSGS may or may not have detectable disease or symptoms of disease according to page 5, line 8-10 of the instant specification; and the FSGS is a glomerulopathy characterized by nephrotic syndrome recites in instant claim 13.
Regarding the limitation of “a non-diabetic subject” in claim 1, said limitation appears to be negative limitation drawn to the treated subject (patient population). In the present case, Yousefinejad et al. is silent that the treated rats have diabetes, thus, it is reasonable to interpret the prior art’s silence as teaching that said prior art does not include rat with diabetes, absent persuasive technical reasons or evidentiary showing otherwise.
Regarding the limitation of “wherein the FSGS is…native FSGS” in claim 3, said limitation further limits the FSGS recites in claim 1. In the present case, the prior art is silent regarding said limitation; However, the claimed limitation will naturally flow from the teachings of Yousefinejad et al., since the same genistein (50 mg/kg body weight genistein) is being administered to the same subject at risk of developing FSGS (see above rejection). Yousefinejad et al. is silent that the treated rats have diabetes and kidney transplant, thus, it is reasonable to interpret the prior art’s silence as teaching that said prior art does not include rat with diabetes and kidney transplant. In other words, by practicing the method taught by Yousefinejad et al., one will also be “treating a non-diabetic subject… at risk of developing focal segmental glomerulosclerosis (FSGS)” and “the FSGS is… native FSGS”, such that the development of FSGS occurred at rat’s own kidney.
Regarding the limitation of “wherein the preparation is administered systemically” in claim 5, the administration of genistein by gavage as taught by Yousefinejad et al. is a type of systemic drug delivery, as evidenced by Serwer et al. (see e.g., abstract).
Regarding the limitation of “wherein the preparation is combined with a further preparation having one or more additional agents” in claim 11, and the limitation of “additional active agents are selected from…cholesterol or triglyceride reducing agents” in claim 12, Yousefinejad et al. clearly teaches the administration of genistein (50 mg/kg body weight) plus L-carnitine (50 mg/kg body weight) to rat with Adriamycin®-induced nephrotic syndrome, which is a subject at risk of developing FSGS; and the L-carnitine taught by Yousefinejad et al. is an additional active agent, and a cholesterol or triglyceride reducing agent as it exhibits reducing effect on both total cholesterol and triglyceride, as evidenced by Abbasnezhad et al. (see e.g., abstract).
Therefore, the claimed invention is being anticipated by Yousefinejad et al.
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.
Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Yousefinejad et al. (Progress in Nutrition, 2019. Vol. 21, Supplement 1: 163-172), in view of Berkenstam et al. (US 2015/0290166 A1; cited in the IDS filed on October 2, 2023).
The teachings of Yousefinejad et al. are set forth above and applied as before.
Yousefinejad et al. does not teach the preparation comprises about 10 to 100 grams of genistein as claimed in claim 7. Yousefinejad et al. does not teach the preparation is administered to the subject as a liquid solution as claimed in claim 9; However, Yousefinejad et al. teaches a solution comprising genistein in CMC (carboxymethyl cellulose dissolved in distilled water) (see e.g., p. 164-165, “Methods “, “Animals and experimental diets”).
Berkenstam et al. teaches a pharmaceutical composition comprising a therapeutically effective amount of at least one crystalline form of genistein according to the invention and a pharmaceutically acceptable carrier (see e.g., [0074]). Berkenstam et al. further teaches the pharmaceutical composition can be in the form of liquid dosage form, such as, inter alia, solution in unit dosage form suitable for simple administration of precise dosages, and the administration may be, for example, orally (see e.g., [0074]; [0083]). Berkenstam et al. further teaches the crystalline genistein sodium dihydrate of the invention possesses excellent stability, and is more soluble in water, aqueous solvent systems and organic solvents than genistein itself (see e.g., [0059]). Berkenstam et al. further teaches “therapeutically effective amount of at least one crystalline form of genistein according to the invention” is generally in the range of about 0.05-about 500 mg/kg; and the actual amount required for prophylaxis or treatment of any particular patient may depend upon a variety of factors including, for example, the disease state being treated and its severity (see e.g., [0076]). Berkenstam et al. further teaches the at least one crystalline form of genistein may be used in the methods of treating a human (see e.g., [0065]).
Regarding the limitation of “the preparation comprises about 10 to 100 grams of genistein” in claim 7, said limitation appears to be drawn to the amount of genistein comprised in the preparation. in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It would have been prima facie obvious to one of ordinary skill in the art at the art at the time the application was filed to modify the method of Yousefinejad et al. as set forth above by substituting the genistein composition of Yousefinejad et al. with the pharmaceutical composition of Berkenstam et al. that comprises about 0.05-about 500 mg/kg of crystalline form of genistein. One would have been motivated to do so, because Berkenstam et al. teaches the pharmaceutical composition comprising a therapeutically effective amount of at least one crystalline form of genistein exhibits excellent stability and better solubility profile than genistein itself, wherein the therapeutically effective amount is generally in the range of about 0.05-about 500 mg/kg; and said crystalline form of genistein can be used in a human subject. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by replacing the genistein composition of Yousefinejad et al. with the pharmaceutical composition of Berkenstam et al. that comprises at least one crystalline form of genistein in the range of about 0.05-about 500 mg/kg would have successfully delivered genistein to the subject that is a human as well as incorporating the benefits of better stability and solubility. Please note if a human subject weights 60 kg, which when calculated by
0.05
m
g
k
g
×
60
k
g
×
1
g
1000
m
g
=
0.003
g
500
m
g
k
g
×
60
k
g
×
1
g
1000
m
g
=
30
g
, gives a pharmaceutical composition comprising crystalline form of genistein in the range of 0.003 g to 30 g, and that renders obvious the limitation instantly claimed.
Regarding the limitation of “the preparation is administered to the subject as…a liquid solution” in claim 9, it would have been prima facie obvious to one of ordinary skill in the art at the art at the time the application was filed to modify the method of Yousefinejad et al. as set forth above by substituting the genistein composition of prior art with the genistein composition in the form of liquid solution taught by Berkenstam et al. One would have been motivated to do so, because Berkenstam et al. teaches the pharmaceutical composition comprising at least one crystalline form of genistein, including the crystalline genistein sodium dihydrate, exhibits excellent stability and better solubility profile than genistein itself; and said pharmaceutical composition can be in liquid dosage form, such as solution. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that by replacing the genistein composition of Yousefinejad et al. with the pharmaceutical composition of Berkenstam et al. in the form of liquid solution would have successfully deliver genistein to the subject as well as incorporating the benefits of better stability and solubility.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHIHYI LEE/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628