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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/18/25 has been entered.
Election/Restrictions
Applicant’s 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 1/18/25 is pending.
Claims 6, 37-40 are pending, of which claim 40 is new.
Claims 1-5 and 7-36 have been canceled.
Claims 6 and 37-40 are under examination.
Claims 6 and 37-40 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.
Similarly, the preambles of claims 39 and 40 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 applicant’s 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.
Claims 6 and 37-40 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.
“HDL” and “LDL” are not defined in the application as filed.
Whereas the standard definitions for “HDL” and “LDL” are “high density lipoprotein” and “low density lipoprotein”, many uses of “HDL” and “LDL” instead refer to the cholesterol content in these lipoproteins, which often is more explicitly noted as “HDL-c” and “LDL-c” or “HDL-C” and “LDL-C”.
In view of the above and the lack of definition in the application as filed, as well as the claim language regarding changes in HDL and LDL toward improving the condition of a subject, and also considering applicant’s 1/18/25 arguments, the examiner is confounded as to whether HDL and LDL in the claims are meant to refer to these classes of lipoproteins per se, see Luscher et al., Circulation Research, January 3, 2014, pp 171-182 as to HDL, or to the cholesterol content in these respective lipoproteins (these clearly distinguished for HDL vs. HDL-C in Luscher). Some references also appear to conflate these terms, using LDL to refer to the cholesterol therein, and HDL to refer to the cholesterol therein, see Cleveland Clinic web pages on Cholesterol Levels, 13 pages, and on HDL Cholesterol, 8 pages, provided.
Consequential to this, it is unclear what is meant by, and what are the metes and bounds of “elevated LDL levels” and “HDL levels” in the claims. While the ordinary and customary level of elevated LDL cholesterol is greater than or equal to 100 mg/dL, and for elevated HDL cholesterol above 80 mg/dL, it is not clear what is meant by these terms in the claims due to the lack of clarity of whether by LDL is meant the lipoprotein or its cholesterol, and by HDL is meant the lipoprotein or its cholesterol.
Claims 6 and 37-40 are rejected on the above bases as being unclear and 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.
Claims 6 and 37-40 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 in a subject without lowering HDL levels in the subject. This method entails identifying the subject with elevated cholesterol levels and elevated LDL levels and administering to the identified subject a fasting mimicking diet (FMD) for a first time period of 1 to 2 days every week. The administration of the FMD for the time period of 1 to 2 days is claimed to reduce both elevated cholesterol levels and reduce elevated LDL levels without lowering HDL 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 day 2 that also includes less than 30 g of sugar on day 1 and less than 20 g of sugar on day 2, less than 28 g of proteins on day 1 and less than 18 g of proteins on day 2, between 20 and 30 grams of monounsaturated fats on day 1 and 10-15 grams of monounsaturated fats on day 2, between 6 and 10 grams of polyunsaturated fats on day 1 and 3-5 grams of polyunsaturated fats on day 2, less than 12 g of saturated fats on day 1 and less than 6 grams of saturated fats on day 2.
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 1 to 2 days a week, reduces elevated cholesterol and LDL levels without lowering HDL levels. The specification does not disclose the claimed fasting mimicking diet providing 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 day 2 that also includes less than 30 g of sugar on day 1 and less than 20 g of sugar on day 2, less than 28 g of proteins on day 1 and less than 18 g of proteins on day 2, between 20 and 30 grams of monounsaturated fats on day 1 and 10-15 grams of monounsaturated fats day 2, 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 day 2 reduces elevated cholesterol levels and LDL levels in a subject with elevated cholesterol and LDL without lowering HDL. 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 a 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 levels without lowering HDL levels in a subject when administered 1 to 2 days per week. The specifics of the FMD that results in reduce elevated cholesterol and LDL levels without lowering HDL levels when administered 1 to 2 days per week are not disclosed and there are no examples disclosed. 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, specifically the administration of the claimed FMD for 1 to 2 days a week for the purpose of reducing elevated cholesterol and elevated LDL levels without lowering HDL.
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 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 levels,” this is stated in line 3 of b) of the claim, and the above analysis, as well as the additional basis below, apply.
As an additional basis of rejection under this section for all of claims 6 and 37-40, considering the range of possible consumption of different food types and specific foods with the claimed genus of FMD allowed by claim 6, 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 day 2 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 day 2 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 to 2 days, 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 day 2 (when day 2 is practiced given that this is not required under claim 6, nor claims 39 or 40). 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 1 to 2 days every week 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 1 to 2 days every week 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 37-40 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.
Response to Arguments
Applicant's arguments filed 1/18/25 have been fully considered but they are not persuasive.
Applicant first argues that Figure 4G plus an inference from a person skilled in the art as to the data and the disclosed dietary composition “that HDL levels remain essentially unaffected.” There is no reference to support this, nor does “essentially unaffected” equate with the claimed “without lowering HDL levels” in claims 6 and 40; essentially unaffected as reasonably interpreted encompasses a lowering albeit a small one. As to further statements in the same paragraph on page 4 regarding the alleged “well-documented” selective lowering of LDL and cholesterol without reducing HDL levels, as to high monounsaturated fat, low sugar and low protein levels, this is given little weight absent provision of the referred to scientific literature, and also given the widely varying genus of particular foods and percentages of carbohydrates, proteins, lipids and fiber encompassed by the claimed FMDs, and resulting range of possible interactions thereof.
As to the last paragraph beginning on page 4, this explanation of what applicant considers its FMD and how it affects metabolism has been considered but does not diminish the bases for rejection set forth in the above rejection. The same applies to further paragraphs arguing against the rejection of claim 6, which repeat some of the assertions addressed above.
Regarding assertions pertaining to claim 39, the single demonstration does not support possession for the genus of possible FMDs encompassed by the claim. The above rejection set this forth in greater detail by providing additional bases that apply to this claim.
This Office action also set forth the confusion and lack of clarity regarding HDL and LDL, which further diminish applicant’s arguments.
For completeness of the record, and also as further support of the bases of the above rejection, the following response previously set forth is retained:
Applicant argues the specification satisfies the written description requirement under 112 (a). Applicant argues Figure 3C shows significant weight loss after 2 days of the FMD which is a marker that the diet is working after a short period time. See p. 5. Applicant continues their argument that the weight loss would be viewed in light of the results shown in Figure 4C that shows a reduction in total cholesterol and LDL. Applicant argues that it is completely logical that total cholesterol and LDL will also be reduced after 2 days of the fasting-mimicking diet (FMD) because Figure 4G suggests a decrease in total cholesterol of -11 mg/dL and in LDL of -8 mg/dL. See pages 5-6 in the remarks filed May 9, 2024.
Applicant’s arguments have been fully considered but are not found persuasive. The claimed method (of claim 6) is directed to lowering elevated cholesterol and elevated LDL without lowering HDL. Figures 3C, 4C and 4G do not show the effect of the FMD on HDL. There is no evidence or teaching (expressly or impliedly) in the specification that the specific diet claimed does not reduce HDL while reducing elevated LDL and total cholesterol. Furthermore, a decrease in cholesterol, LDL or even weight loss, is not coextensive with not lowering HDL. The prior art is replete with many instances showing patients with elevated LDL and cholesterol that make a lifestyle modification like modifying their diet, reduce their levels of LDL, cholesterol and weight in addition to reducing their HDL. See for example, Brown et al.,1 Brown et al. correlated fasting glucose, triglyceride, LDL, HDL and cholesterol with weight loss from data from overweight and obese adults with elevated LDL and cholesterol. Brown et al. observed patients that lost >10 % of their weight saw significant reductions in all five risk factors, including HDL cholesterol, an undesirable change. See p. 342, §Relation of degree of weight loss to level of risk improvement- 2nd ¶). Furthermore, with regard to Figures 3C, 4C and 4G, the specifics of the compositions (structure) of fasting mimicking and enhancing diet administered to the mice in Figure 3C and healthy participants in Figures 4C and 4G is unclear and the duration of the FMD that was administered to the mice and healthy participants is not 1 to 2 days every week as claimed. Thus, without knowing the specifics of the FMD administered and the lack of disclosure with regard to lowering HDL, the skilled would conclude Applicant was not in possession of the claimed invention as the time of filing. Therefore, for the reasons set forth above, the claims 6, 37 and 38 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
(end of retained response)
Conclusion
No claim is allowed.
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.
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/Joseph Fischer/
Examiner
Art Unit 1658
1 Brown et al., “Effects on cardiovascular risk factors of weight losses limited to 5–10 %”, TBM, 2016; pp. 339-346, previously provided.