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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 1/18/25 has been entered.
Election/Restrictions
Applicants’ election without traverse of the species of intended method purpose as for reducing elevated cholesterol levels and/or elevated LDL levels without lowering HDL levels in the reply filed on October 21, 2022, is acknowledged.
Priority
The instant application, filed 02/16/2021 and having 2 RCE-type filing therein is a Divisional of 15148251 , filed 05/06/2016, now U.S. Patent # 11000057 and having 2 RCE-type filing therein
15148251 Claims Priority from Provisional Application 62157602 , filed 05/06/2015.
Claim Status
The claim listing filed 4/20/26 is pending.
Claims 6, 37-41 are pending, of which claim 41 is new.
Claims 1-5 and 7-36 have been canceled.
Claims 6 and 37-41 are under examination.
Claims 6 and 37-41 are rejected.
Claim Interpretation
The claim limitations are given their broadest reasonable interpretation (BRI) consistent with the specification, MPEP 2111, and under the BRI, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification, MPEP 2111.01.
Claim 6’s preamble states that the method is “for reducing elevated cholesterol levels and elevated LDL levels without lowering HDL levels.” This preamble language is reasonably interpreted to result in a manipulative difference between the claimed invention and the prior art, and accordingly serves to limit the claim, see MPEP 2111.02 II. (Note that 4/20/26 claims have been amended to LDL cholesterol and HDL cholesterol levels, and this amended preamble language also is reasonably interpreted to result in a manipulative difference between the claimed invention and the prior art, and accordingly serves to limit the claim.)
Similarly, the preambles of claims 39 and 40 (as amended 4/20/26, and also new claim 41) also are reasonably interpreted to result in a manipulative difference between the claimed invention and the prior art, and accordingly serve to limit each such claim, see MPEP 2111.02 II.
These methods’ preamble objectives to obtain the manipulative difference over the prior art also are distinguished from other of applicant’s claims’ purpose or intended use language at least because this is a clear objective toward which the data, such as it may exist, and other disclosure in the application is directed, see also MPEP 2111.02 II, and also MPEP 2112 IV. This also is consistent with distinctions made in other of applicants’ patent applications directed to different therapeutic objectives.
With regard to the instant claims’ use of “elevated cholesterol levels”, based on what is routinely used in the art, “elevated cholesterol levels” is interpreted as equal or greater than 200 mg/dL.
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.
Response to Arguments
Applicant’s arguments, see pages 5-6, filed 4/20/26, and claim amendments with respect to the rejection(s) of claims 6 and 37-40 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite have been fully considered and are persuasive in part (Applicant never responded directly to the sentence in the 10/21/25 Non-final rejection under this section that began with “Consequential to this…”, perhaps because it was considered moot given the amendment to “elevated LDL cholesterol”, however the fundamental issue for the latter remains, as set forth below). The examiner accepts that Fig. 4G supports LDL means LDL cholesterol, and correspondingly reference to HDL reasonably reference to HDL cholesterol (although there is no explicit support for this).Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the claim amendments, presenting newly identified issues based on such amendments.
Claims 6 and 37-41 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.
While there may be a standard in the art for “elevated LDL levels”, there is no provision in the application as filed, and the examiner has not identified any clear standard for a level of LDL cholesterol that is “elevated.”
The examiner searched and found two references:
From Cleveland Clinic, pages 2-3 (copy of printed version of webpage provided herewith):
PNG
media_image1.png
437
409
media_image1.png
Greyscale
From Johns Hopkins, pages 3-4 (copy of printed version of webpage provided herewith):
PNG
media_image2.png
593
1131
media_image2.png
Greyscale
Based on these sources, what is elevated to Cleveland Clinic is near optimal to Johns Hopkins.
The term “elevated” is deemed a relative term having a value and range that are not clearly established in the art, and the meaning of “elevated” as applied to LDL cholesterol was not defined in the application as filed. As such the metes and bounds of what is claimed in claims 6 and 37-41 are unclear and the claims accordingly indefinite.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Response to Arguments
Applicant arguments filed 4/20/26 have been fully considered but they are not persuasive.
As to point 1, pages 6-7, one demonstration is not representative of the breadth of possible food combinations that meet the limitations of the claims, see rejection below.
As to point 2, pages 7-8, applicant’s (or applicant’s attorney’s) statements regarding lists of food ingredients in the specification, but not in the claims, are unpersuasive because these are not in the claims in any ranges or amounts. As to what is “well recognized in the nutritional and medical arts”, page 7, for monounsaturated fats from nut and olive sources, has not been substantiated, and the applicant/attorney is silent about the effects of variations in particular components, beyond macro levels of types of lipids, in any of these food sources.
As but one example of the significance of variations in particular components, Colpo et al., Journal of Nutrition and Metabolism, Volume 2013, Article ID 653185, 7 pages, teaches that a single dose of Brazil nuts significantly reduces serum LDL cholesterol, and HDL cholesterol was significantly higher 9 hours after a single ingestion of 20 or 50 grams of Brazil nuts, Background. A great deal of the article pertains to selenium levels, however these did not vary significantly based on amount ingested, and on page 4 Colpo raises the question that “of whether the beneficial effects of Brazil nut on the atherogenic index may be due to factors other than selenium (MUFA and PUFA perhaps), highlighting the importance of studying the separate and combined effect of selenium and fatty acids on atherogenic indexes.”
Further, although Colpo generalizes that “Unsaturated fatty acids (both mono and polyunsaturated) have been shown to reduce serum TCz and LDL-c,” page 4 bottom right column, the article continues to distinguish, after stating that Brazil nuts have a relatively higher content of SFAs (saturated fatty acids), stating “Therefore, the increase in HDL-c observed in this present study may be attributed to the higher UFA and SFA content in Brazil nut [52]. According to Riccardi et al. [53], SFA and MUFA increase HDL-c, whereas high intakes of PUFA decrease HDL-c. Unsaturated fatty acids have been shown to increase HDL-c less than SFAs do [54]. Furthermore, while the unsaturated fatty acid profile of nuts (high MUFA and PUFA) is thought to mediate the majority of the beneficial effects of nuts on serum lipids, other components such as fiber and selenium might contribute to these effects [14, 26, 31, 55].”
Apart from considering, based on Colpo’s actual data, that merely eating Brazil nuts may be as effective and simpler than the claimed FMD regimen and more effective to achieve decreases in LDL cholesterol and increases in HDL cholesterol, see Figures 2 and 3, the data and discussion support that many factors other than the levels set forth in the claims, may contribute to (or detract from) a desired result with regard to total, LDL and HDL cholesterol levels.
Further regarding discussion of Brown by applicant, which was provided in a previous Response to Arguments and does not appear in the rejection, and also considering the data in Colpo, the examiner notes that applicant has not set forth in the claims when or for what period of time (during or how long after) the changes are measured. So the changes as currently claimed appear to be at any time after such claimed regimen. In any case, Brown is not in the rejection and does not form the basis of the issue regarding a lack of possession of the multitude of possible specific food components encompassed by what is claimed, that is, the genus, which is addressed in point 3 of the Remarks.
As to point 3, pages 8-9, applicant’s (or applicant’s attorney’s) statements have been considered but are not persuasive. Given effects of micro ingredients, such as trace metals, and also considering the importance of the unclaimed macro ingredient class of fiber, including soluble fiber, the examiner is not persuaded by the statement that “the claims as amended define a tightly constrained dietary regimen,” page 8. Applicant has not provided sources that provide sufficient evidentiary weight to overcome the bases of the rejection, for example there are no reference sources provided that support “it is the fat composition and caloric restriction that drive the selective LDL cholesterol reduction” that would effectively counter the effects of any number of other micro ingredients and macro ingredient fiber, that are not claimed, that could contribute or reduce the effect of the components’ limitations found in the claims. Citing to a “person of ordinary skill” as to what such person would understand does not provide high-weight evidence.
One final point. On days 2-5 of the claimed FMD regimen the minimum REQUIRED specific component intakes are 10 g monounsaturated fats and 3 g polyunsaturated fats, with an allowed 5 kcal/pound of subject caloric intake. A 150-pound subject could consume 750 calories per day of days 2-5, and of this only about 117 calories is attributed to the 10 g monounsaturated fats and 3 g polyunsaturated fats. If white rice, which has a proximate analysis of about 80% carbohydrate, 7% protein and less than 1% crude fat, were consumed with the 10 g monounsaturated fats and 3 g polyunsaturated fats for days 2-5, up to the maximum limit imposed by calories or protein content (by the examiner’s quick, approximate calculation, this would be 140 g white rice per day (dry weight, before cooking) providing just under 10 g protein, so within the claims’ limitations), given the lack of soluble fiber which per the examiner’s understanding traps and removes cholesterol from the body, such diet which falls within the breadth of what is claimed reasonably, from a technical standpoint, would not achieve the claimed manipulative difference result (at least in part due to the lack of soluble fiber to remove cholesterol in the intestine). The examiner understands that the examiner cannot prove this – the Patent Office does not have laboratories or conduct such types of research, however, sets it forth for further consideration by applicant.
Claims 6 and 37-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To demonstrate possession of the claimed invention:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
…
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the inventor was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed.
MPEP 2163 II A 3 ii), see also 2163 in its entirety.
The invention presently claimed in claim 6 is directed to a method for reducing both elevated cholesterol and elevated LDL cholesterol in a subject without lowering HDL cholesterol levels in the subject. This method entails identifying the subject with elevated cholesterol levels and elevated LDL cholesterol levels and administering to the identified subject a fasting mimicking diet (FMD) for a first time period of 5 days every 2 to 4 weeks. Such administration of the FMD is claimed to reduce both elevated cholesterol levels and reduce elevated LDL cholesterol levels without lowering HDL cholesterol levels. The claimed FMD comprises a total calorie consumption of 4.5-7 kcal per pound of the subject for day 1 and 3-5 kcal per pound of the subject for days 2-5 that also includes less than 30 g of sugar on day 1 and less than 20 g of sugar on days 2-5, less than 28 g of proteins on day 1 and less than 18 g of proteins on days 2-5, between 20 and 30 grams of monounsaturated fats on day 1 and 10-15 grams of monounsaturated fats on days 2-5, between 6 and 10 grams of polyunsaturated fats on day 1 and 3-5 grams of polyunsaturated fats on days 2-5, less than 12 g of saturated fats on day 1 and less than 6 grams of saturated fats on days 2-5.
New claim 41 comprises the same regimen, however, is directed only for reducing elevated cholesterol levels and elevated LDL levels and is silent regarding “without lowering HDL cholesterol levels”.
There is no indication in the disclosure that Applicant was in possession of the presently claimed method because there is no support, impliedly or explicitly, that administering the claimed FMD, including across the genus of specific dietary regimens encompassed by the claim (see additional basis below), for 4-5 days every 2 to 4 weeks, reduces elevated cholesterol and LDL cholesterol levels, regardless (as to claim 41) or without lowering HDL cholesterol levels. The specification does not disclose that the claimed fasting mimicking diet reduces elevated cholesterol levels and LDL cholesterol levels in a subject with elevated cholesterol and LDL cholesterol without lowering HDL cholesterol. The latter was never determined in any test in the application as filed. The specification discloses in paragraph [0031] a general method for elevated cholesterol and/or elevated LDL without lowering HDL levels in a subject which includes administering for a first time period an FMD. There is no disclosure of the structure of a FMD reduced to practice that reduces elevated cholesterol and LDL without reducing HDL.
The examiner notes that in a word search of corresponding PGPUB No. 20210161191 “HDL” was found twice, in para 32 and claim 6, “lipoprotein” was not found, and based on perusal of the drawings there was no reference to HDL. As to LDL, this was found 8 times in paras 12, 32 (including with reference to without reducing HDL), 64 (referring to Figure 4, which depicts the only data of LDL reduction based on a single experiment), and claim 6.
Even though the specification discloses an embodiment of a diet, see paragraph [0049], where the diet provides the following: 4.5 to 7 kilocalories per pound of subject for a first day and 3 to 5 kilocalories per pound of subject per day for a second to fifth day of the first diet; rations that provide less than 30 g of sugar on the first day; less than 20 g of sugar on the second to fifth days; less than 28 g of proteins on the first day; less than 18 g of proteins on the second to fifth days; 20 to 30 grams of monounsaturated fats on the first day; 10 to l5 grams of monounsaturated fats on the second to fifth days; between 6 and 10 grams of polyunsaturated fats on the first day; 3 to 5 grams of polyunsaturated fats on the second to fifth days; less than 12 g of saturated fats on the first day; less than 6 grams of saturated fats on the second to fifth days; and 12 to 25 grams of glycerol per day on the second to fifth days; there is no indication in the specification that implies or explicitly states this specific diet reduces elevated cholesterol and elevated LDL cholesterol levels regardless of or without lowering HDL levels in a subject when administered 4 to 5 days per week every 2 to 4 weeks. Therefore, at least for the reasons set forth above, one of ordinary skill in the art would conclude the specification fails to satisfy the written description requirement under 112(a) for claim 6 because there is no support that Applicant was possession of claimed method to achieve what the claims state. At a minimum there is no data for HDL cholesterol levels before, during or after the FMD regimen.
The above analysis and observations also apply to claims 37 and 38 which depend from claim 6.
The above analysis is modified for claim 39 as follows. Claim 39 does not require “without lowering HDL cholesterol levels.” However, apart from this, the single demonstration of reduction for a single formulation does not provide possession for the breadth of encompassed FMDs at least based on the additional basis below.
Regarding claim 40, although the preamble does not require or note “without lowering HDL cholesterol levels,” this is stated in line 3 of b) of the claim, and the above analysis, as well as the additional basis below, apply.
Regarding new claim 41, the additional basis, immediately below, applies.
As an additional basis of rejection under this section for all of claims 6 and 37-41, considering the range of possible consumption of different food types and specific foods with the claimed genus of FMD allowed by claim 6 (and also applying to claims 39-41 as amended), the examiner first notes
The only absolute requirements for specific food class consumption during day 1 is to consume between 20 and 30 grams of monounsaturated fats and between 6 and 10 grams of polyunsaturated fats, and during days 2-5 is to consume between 10 to 15 grams of monounsaturated fats and between 3 to 5 grams of polyunsaturated fats;
The remainder of the foods to meet the total calorie consumption of 4.5-7 kcal per pound of the subject for day 1 and 3-5 kcal per pound of the subject for days 2-5 can include any quantity and proportion relative to other intake of digestible complex carbohydrates as well as any amount of fiber;
When considering the above and the claim limitations for protein, sugar and saturated fats, there is a very wide range of possible diets that fall within the genus of diets encompassed by the claim limitations; and
For subject of widely differing body weights, the relative proportion of monounsaturated fats and polyunsaturated fats to total caloric intake for these two days will fluctuate widely.
That is, apart from the kilocalories per pound limitations for the 1-5 days of each FMD regimen, the only closed-range limitations are for monounsaturated fats and polyunsaturated fats, and a closed range limitation of 12-25 grams for day for glycerol when considering claim 37. This leaves a wide range of fiber and complex carbohydrates that can provide the remainder of the calories along with the claim-limited amounts of protein, sugar and saturated fat, to provide a total caloric intake within the range of 4.5 to 7 kcal per subject pound for day 1, and 3 to 5 kcal per subject pound for days 2-5. For example, fiber at about 2 calories per gram of fiber by intestinal microbial conversion convert to short chain fatty acids per UMich 4 Ways Fiber Benefits Your Health, 2017, 1 page, and could be added along with a varied combination of protein, sugar and saturated fats so long as the latter three remain below the claim limitations. This would reasonably alter the effect of this dietary regimen, as would any of a huge number of variations of selected food combinations that for each combination meets the claim limitations, such as specific foods ranging from Brazil nuts to French fried potatoes to wheat grass juice, as well as specific combinations such as nothing but bread and the required fats with wine (no specific limitations on alcohol), resulting in hundreds if not thousands of possible food selections and combinations. Even assuming, arguendo, there is a possession based on a single evaluation for the claimed invention (which the examiner as set forth above concludes that there is not), such single species would be neither representative nor commensurate with the wide and diverse species that fall within the genus of claimed fasting mimicking diet.
Further, for a subject having below average body weight, in the claimed age range, the claimed limitations for monounsaturated fats, polyunsaturated fats and glycerol would reduce other contributions disproportionally, and this adds to the multiple diverse nutrient combinations within the claimed subgenus of the periodically administered low protein diet. There is insufficient support for the periodic administration of such a wide range of “fasting mimicking diets (FMD)” to have the claimed effects/results in a subject. Conversely, for a very heavy subject, over 1 or 2 standard deviations from average in the age range, the upper limits on sugars, protein, fats, and even glycerol would skew the remaining components, such as fiber and complex carbohydrates, to present to that subject a different type of diet during the 5 days every 2 to 4 weeks compared to an average or below average body weight subject. Again, there is insufficient support for the periodic administration of the widely varying in components consequent types of “fasting mimicking diets (FMD)” to demonstrate the claimed effects/results in a subject, including when applied to the diversity of subjects – having different weights, genetic predispositions, and diets apart from on the 5 days every 2 to 4 weeks of FMD.
In summary, the description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.") Based on the above, in whole or in part, there is a lack of possession for all of the claims under examination. Accordingly, for the reasons above it is deemed that the specification fails to provide adequate written description for claims 6 and 37-41 and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH FISCHER whose telephone number is (571)270-7925. The examiner can normally be reached on Monday to Friday, 9:00 AM to 5:00 PM, however noting that the examiner will not normally be working on Wednesday-Friday and on Monday/Tuesday on alternating weeks, but will promptly answer messages upon his return to work.
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, MELISSA FISHER, can be reached on 571-270-7430. 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.
/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
Prosecution Insights