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 .
DETAILED ACTION
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 06/08/2026, wherein independent claims 8 and 11 are amended to recite “wherein digestion of the composition generates butyrate in an amount effective for treating overweight and/or obesity in the individual through enhancement of energy expenditure and induction of mitochondrial function”.
Instant spec (See [0005]) discloses “The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondria function”. However, the amended limitation drawn to mechanism/intended function of butyrate does not further limit the step of administering instant claimed triglyceride composition for method of treating obesity/overweight.
Election/Restriction
Applicant elected without traverse of Group II (method for weight management), and combination species of compounds having formula (5) and (6) on 12/13/2024.
Status of Claims
Claims 1-20 are pending in the instant application.
Claims 1-7, 10, and 13 remain withdrawn as being drawn to a nonelected invention/species, there being no allowable generic or linking claim.
Claims 8, 9, 11, 12, and 14-20 are currently under examination.
Action Summary
Applicant's Remarks filed 06/08/2026 have been fully considered.
Applicant’s arguments regarding 35 U.S.C. § 112 (a) enablement rejection and 35 U.S.C. § 103 rejection over Wheeler in view of Klemann and Finley have been fully considered, but are NOT persuasive. Please see following Response to Argument.
US application Nos 17/595,539; 17/595,567 and 17/595,629 are abandoned. Thus, the provisional nonstatutory double patenting rejections over US application Nos 17/595,539; 17/595,567 and 17/595,629 in view of Wheeler are withdrawn.
The provisional nonstatutory double patenting rejections over 17/044,684;17/413,991 (now US patent No.12667552); 17/595,451; 17/595,516 (now US patent No.12661334); 17/756,871(now US patent No. 12648923) ; and 17/756,872 in view of Wheeler are maintained/ reapplied necessitated by the amendment/status change of reference applications.
Priority
This application 17/595,446 filed on 11/17/2021, is a national stage of international application No. PCT/EP2020/064077, filed on May 20, 2020, which claims priority to European Patent Application No. 19175540.4, filed on May 21, 2019.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of European Patent Application No. 19175540.4 was filed on 11/17/2021.
Claim interpretation
Instant claims are amended to a method for treating overweight and/or obesity in an individual in need thereof, comprising administering composition comprising a mixture of triglycerides having formula of (5), (6), (7), (8) and other triglyceride recited in claim 14 with common names. Instant specification discloses nomenclature of instantly claimed triglycerides (See page 20, Example 1).
Instant claimed triglyceride formula (5) ( CAS # 175878-34-9, entered STN on 05/02/1996), is also known as 1,3-dibutyryl-2-oleoyl glycerol, TG 4:0/18:1/4:0, 1,3-butyrin-2-olein (See STN searched note, Cayman catalog). Triglyceride formula (5), i.e. TG 4:0-18:1-4:0, comprises two butyrate short chain moiety and one unsaturated 18:1 moiety (SUS).
Instantly claimed compound of formula (6) (CAS # 145135-35-9, entered STN on 12/31/1992), is also known as 1,2-dioleoyl-3-butyryl glycerol, 1,2-olein-3-butyrin (See STN searched note).Triglyceride formula (6), i.e. TG (18:1-18:1-4:0), comprises two 18:1 unsaturated moiety and one butyrate short chain moiety( SUU or UUS).
Instantly claimed butyrate moiety containing triglycerides are a mixture of multiple triglyceride with variety of structures, wherein TG 4:0-18:1-4:0 is about 16.2-27%, TG 18:1-18:1-4:0 is about 23.3-25.8%(See page 20, Example 1, Table 1).
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It’s noted instant claimed butyrate moiety containing triglycerides was generated by chemical interesterification between tributyrin and high oleic sunflower oil in the presence of catalyst. Generally speaking, chemical interesterification are unpredictable due to a variety of factors, e.g. the catalyst, the ratio of oleic acid to tributyrin, etc., and different batch of oleic sunflower oil might generate triglyceride composition comprising different triglyceride at different ratio that are different from instant claimed composition.
Although instant claims recite formula (5) and formula (6) as the major component of butyrate moiety containing triglycerides, instant composition is a mixture of triglycerides comprising variety combination of different acid moiety (4:0, 16:0, 18:1, 18:2, etc.) at different positions. The alleged activity/ function of instant composition for use in treating obesity or overweight is construed as result of combination of butyrate moiety containing triglycerides that is NOT contributed/limited only by the properties of formula (5) and formula (6) alone.
Please note the amended limitation drawn to mechanism/intended function of butyrate does not further limit the step of administering instant claimed triglyceride composition and does not necessarily contribute to the patentability of instant claimed method of treating obesity/overweight.
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.
Scope of enablement rejection
Claims 8, 9, 11, 12, and 14-20 are rejected under 35 U.S.C. 112(a) first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The specification, while enabling for a method of providing a source of butyrate to an individual in need thereof with instantly claimed triglyceride comprising butyrate moiety, does not reasonably provide enablement for a method for treating overweight or obesity in an individual via administering instantly claimed triglyceride combination/mixture in full scope (newly reapplied as necessitated by amendment).
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). The determination that "undue experimentation" would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The Breadth of The Claims/ Nature of The Invention
Independent claims 8 and 11 are amended to a method for treating overweight and/or obesity in an individual in need thereof, comprising administering composition comprising compounds having the formulas (5) and (6)… to an individual, and wherein digestion of the composition generates butyrate in an amount effective for treating overweight and/or obesity in the individual through enhancement of energy expenditure and induction of mitochondrial function. Both instantly claimed formula (5) and (6) contain butyrate and oleoyl moiety. Instant specification discloses digestion profile of butyrate moiety containing triglyceride through in-vitro lipolysis assay (Example 5). Instant claims might be enabled for a method of providing a source of butyrate to a subject in need thereof with instantly claimed triglyceride comprising butyrate moiety. However, treating overweight or obesity is a very broad, umbrella term that involves many variable/factors, e.g. diet, disease, medications, physical exercise, etc. Different subject would have different response to the butyrate containing triglyceride. Please note instant claims are directed to triglycerides mixture composition per se , not any butyrate that might be generated once digested that might be responsible for providing an effect relevant to weight control. Although instant specification disclosed digestion profile of instantly claimed composition, digestion is only small portion of butyrate diet which also involves absorption, distribution, metabolism, etc. The digestion profile does not necessarily correlate with weight loss and/or treating overweight. As such, instantly claimed method for treating overweight and/or obesity by administrating butyrate triglyceride in absence of sufficient evidence associated with weight loss data and dosage/administration regimen is not enabled for the full scope.
The State of the Prior Art and the Predictability or Lack Thereof in the Art
First, instant claimed butyrate moiety containing triglycerides was generated by chemical interesterification between tributyrin and high oleic sunflower oil in the presence of catalyst. Generally speaking, chemical interesterification are highly unpredictable due to a variety of factors, e.g. the catalyst, the ratio of oleic acid to tributyrin, etc., and different batch of oleic sunflower oil might generate composition of triglyceride comprising different triglyceride at different ratio that’s different from instantly claimed composition comprising formula (5) and (6). See Da Silva (2010): chemical interesterification results in a random distribution of fatty acids and this effect can be observed by the similarity of the sn-2 and sn-1,3 positions after the rearrangement. As a consequence, after interesterification the blends presented an increase on the amount of saturated fatty acids and a decrease of unsaturated fatty acids in the sn-2 position (page 758, left column).
Second, it’s well-known treating obesity/overweight is unpredictable wherein vast variety of factors have impact on the weight of individual, e.g. diet, physical exercise, disease, etc. See Cannon (2009). The efficacy of treating overweight/obesity by dietary triglyceride is unpredictable due to a variety factors including chemical structures/ physical properties of the triglyceride composition, delivery/absorption/ digestion profile, individual conditions, etc.
Regarding butyrate triglyceride diet use for weight control, although some study report metabolic effect of butyrate source might be positively associated with weight control , the mechanism underlying the metabolic benefit of butyrate on weight control was still contradictory. Liu (2018) reviews butyrate’s potential effects and mechanisms involved in intestinal health and obesity. Although butyrate plays an important role in gut health, the effect of butyrate on obesity remains controversial (See Introduction, page 21, right column, Table 2, Conclusion). Liu and its incorporated reference teaches short chain fatty acid SCFA/butyrate “ are rapidly assimilated into host carbohydrates and lipids and could contribute to the obese phenotype by providing ∼10% of our daily energy requirements… butyrate is able to increase lipid synthesis from acetyl-CoA or ketone bodies via the β-hydroxy-β-methylglutaryl-CoA pathway, which potentially contributes to obesity” (page 25, right column, Inducing obesity). “ In conclusion, although a large body of evidence has suggested the effect of butyrate on alleviating high fat diet–induced obesity and insulin resistance, a few studies showed an opposite effect. Therefore, additional investigations are
warranted to understand the apparently paradoxical effects of butyrate on obesity” (See page 26, left column). Liu concludes “The reason behind the paradoxical effect of butyrate on glucose and lipid metabolism, especially with regard to its role in obesity, remains elusive” (See Conclusions, page 26).
More generally, the invention is directed toward physiological activity in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The Amount of Direction Present and Presence or Absence of Working Examples
Instant specification discloses preparation of butyrate moiety containing triglyceride regioisomer profile (See page 20, Table 1, Example 1) comprising 4:0-18:1-4:0 (i.e. formula 5) and 18:1-18:1-4:0(i.e. formula 6), and variety of other triglyceride components comprising different acid moiety (4:0, 16:0, 18:1, 18:2, etc.) at different positions. Instant specification discloses digestion profile of butyrate moiety containing triglyceride through in-vitro lipolysis assay (Example 5).
Instant specification only discloses sodium methanoate as exemplary catalyst without ratio/amount in chemical interesterification (See Example 1). Instant specification does not disclose any assay associated with formula (5), or formula (6) alone or combination thereof. Instant specification does not disclose any assay/weight data of individual administered with instantly claimed formula (5) and formula (6). Although instant claims recite formula (5) and formula (6) as the major component of butyrate moiety containing triglycerides, instant composition is a mixture of triglycerides comprising variety combination of different acid moiety (4:0, 16:0, 18:1, 18:2, etc.) at different positions as seen from Table 1. The alleged activity/ function of instant composition for use in weight control is the result of combination of butyrate moiety containing triglycerides that is NOT contributed/limited only by the properties of formula (5) and formula (6) alone. Since different butyrate moiety containing triglyceride has different pharmacokinetic profile (absorption, digestion, etc.), an ordinary skilled in the art would not know how much butyrate is released from which butyrate-containing triglyceride component, formula (5), or formula (6), or other butyrate moiety containing triglycerides. An ordinary skilled in the art would not know what’s the specific contribution to C4 butyrate digestion profile are associated with formula(5) and formula (6). In absence of sufficient weight data associated with formula (5) and formula (6), instantly claimed composition comprising formula (5) and formula (6) for use in weight control is not fully established and enabled by instant disclosure. Please note the digestion profile does not necessarily correlate with weight loss and/or treating overweight. More importantly, instant claims are directed to triglycerides per se , not any butyrate that might be generated once digested that might be responsible for providing an effect relevant to weight control.
The level of one of ordinary skill in the art
The level of skill required to make and/or use the instant invention would likely require years of professional experience conducting research in the art (e.g., medicine, pharmaceutical science, biology, biochemistry, medicinal chemistry, and/or organic chemistry, etc.) as well as an advanced educational degree (e.g., M.D. and/or Ph.D.) commensurate in level with the advanced techniques involved in the preparation and/or use of the instant invention.
The quantity of experimentation needed
It would be a burden for one of ordinary skill in the art to carry out undue experimentation to use the claimed invention in full scope. First, an unduly amount of experimentation might be needed for one of ordinary skill in the art to develop inter-esterification protocols to generate instant claimed triglyceride composition at instant claimed ratio due to the unpredictability of inter-esterification. Second, an unduly extensive amount of experimentation would be required for one of ordinary skill in the art to test the effectiveness of instantly claimed method of treating overweight/obesity in an individual. In-vivo experiment on individual/subject would be needed to evaluate the efficacy of instantly claimed method of treating overweight/obesity in an individual. The effective amount may vary depending on many factors, such the physical properties, absorption profile of the triglyceride combination/mixture, individual conditions etc. More assay would be needed to evaluate the safety profile for instantly claimed use in infant formula.
Conclusion
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562,27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here with respect to the claimed method of treating overweight/obesity in an individual comprising administering compounds having the formulas (5) and (6), in view of the analysis above pursuant to In re Wands. In other words, one skilled in the art could not practice the claimed invention without undue experimentation.
Response to Arguments
Applicant's arguments filed 06/08/2026 have been fully considered, but they are not persuasive.
Applicant argues about the state of the prior art and the predictability or lack thereof in the art: Liu clearly indicates that most of the evidence supports that butyrate can be used to alleviate the effects of obesity, and thus from reading this document the skilled person will understand that butyrate has a therapeutic effect against obesity. As such, based on the disclosure of Liu, Applicant submits this factor favors a finding of enablement.
RESPONSE: As indicated in previous office action, the examiner does not dispute that butyrate might be associated with weight control according to Liu. However, Liu also discloses a few studies showed an opposite effect that butyrate induce obesity (Liu, page 25, right column), therefore additional investigations are warranted to understand the apparently paradoxical effects of butyrate on obesity (Liu, Table 2; page 26, left column). Thus, the method of treating obesity with butyrate is considered as unpredictable.
More importantly, instant claims are directed to a mixture of butyrate triglycerides per se, not any butyrate that might be generated once digested in an effective amount for treating overweight/obesity.
Applicant argues the claimed triglycerides undergo complete hydrolysis in vivo, thereby releasing all butyrate moieties bound within the respective triglycerides... the skilled person would be readily able to determine an appropriate therapeutically effective dose as discussed in the application as filed.
RESPONSE: Please note instant disclosed assay is NOT in vivo as Applicant argued. Instant disclosed Example 5 is in vitro lipolysis with sequential SGF (RGL) SIF (PPL) digestion model , i. e. Simulated Gastric Fluid (SGF) with rabbit gastric lipase (RGL) or pepsin, followed by Simulated Intestinal Fluid (SIF) with porcine pancreatic lipase (PPL). It’s noted instant claimed total digestion was done by simulated digestion model back titration at pH 11.5 while many fatty acids are only partially ionized at pH 6.8(See [0173]). Thus, instant disclosed digestion profile is not considered as accurately representative or reflective of digestion in the normal pH of intestine as instant specification alleged (See [0174]). As such, instant lipolysis assay/ digesting profile does not necessarily correlate with treating obesity/overweight in vivo.
Regarding the effective amount of dose , instant specification (page 10, lines 17-21 ) only disclose:
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Instant specification does not disclose any dosing regimen for instant claimed butyrate triglyceride composition. Instant specification does not disclose what amount of butyrate could be generated from what amount of instant claimed composition. Instant claims 8 and 11 recite composition comprising formula (5) and formula (6) at least 10% by weight of the total triglyceride or butyrate moiety containing triglyceride, wherein butyrate generated from the instantly alleged full butyrate moieties is not representative or correlates with butyrate generated from formula (5) and formula (6) alone or combined. In other words, an ordinary skilled in the art would not know what amount of instant claimed composition could generate effective amount of butyrate to exhibit efficacy of treating obesity in a subject/individual. An unduly extensive amount of experimentation would be required for an ordinary skilled in the art to test the effectiveness of instantly claimed method of treating overweight/obesity in an individual. In-vivo experiment on individual/subject would be needed to evaluate the efficacy of instantly claimed method of treating overweight/obesity in an individual. In other words, even if instant claimed composition could generate butyrate upon digestion, one skilled in the art could not practice the claimed invention without undue experimentation.
Applicant argues the level of one of ordinary skill in the art and the quantity of experimentation needed: examples disclose a straightforward interesterification reaction to produce a composition falling within the scope of the claims. Accordingly, preparation of the claimed inventions does not require undue or unreasonable experimentation for those skilled in the art... with respect to use of the invention, the skilled person needs only administer the claimed composition to a subject in need thereof in order to practice the claimed method.
RESPONSE: As explained above, the triglyceride component/ mixture of instant claimed composition are affected by interesterification reaction which involves many factors, e.g. the component of starting material , temperature, catalyst, etc. The various triglyceride mixture comprising different butyrate triglyceride at different amount encompassed by instant claims might not generate effective amount of butyrate that would exhibit efficacy of treating obesity/overweight.
More importantly, the efficacy of instant claimed composition mixture for treating obesity/overweight is not fully established and supported by instant disclosure. Instant claimed composition is a mixture of triglycerides comprising variety combination of different acid moiety (4:0, 16:0, 18:1, 18:2, etc.) at different positions as seen from Table 1. The alleged activity/ function of instant composition for treating obesity or overweight is the result of combination of butyrate moiety containing triglycerides that is NOT limited only by the properties of formula (5) and formula (6) alone. In absence of sufficient weight data/assay associated with triglycerides formula (5) and formula (6) directly, an ordinary skilled in the art would not know if formula (5) and formula (6) would exhibit any effect on weight control, and /or what’s the dosage regimen/amount for the alleged method of treating overweight/obesity with instant composition comprising mixture of other triglycerides.
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 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 non-obviousness.
Claims 8, 9, 11, 12, and 14-20 remain rejected under 35 U.S.C. 103 as being unpatentable over Wheeler et al.(US 5662953, Applicant’s IDS dated 11/17/2021), in view of Finley et al. ( US 2004/0086621 A1, Applicant’s IDS dated 08/10/2023) and Klemann et al.( US 2009/0123634 A1, Applicant’s IDS dated 11/17/2021) (newly reapplied as necessitated by amendment).
Regarding the instantly claimed combination/mixture of triglycerides, Wheeler teaches low calorie triglyceride comprising long residue (e.g. stearyl, oleoyl ) and short residues(e.g. acetyl, butyryl), composition/mixture of triglyceride having LSS, SLS, LLS, LSL components, and methods of using aforementioned low-calories triglycerides mixtures for reducing calories in food product (See abstract, Col. 5, lines 35-65; claims 1-31). (Please note instantly claimed formula (5) and (6) is SLS, LLS respectively).
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Regarding butyrate moiety, Wheeler teaches various low calorie triglycerides comprising butyrate moiety(See Example 51, Col. 51 to Col. 54):
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Wheeler teaches butyryl-stearoyl glyceride mixture comprising dibutyryl-stearoyl glyceride and butyryldistearoyl glyceride, e.g. 1, 3-dibutyryl-2-stearoyl glycerides, 1, 2-dibutyryl-3-stearoyl glyceride, 1-butyryl-2, 3-distearoyl glyceride, 2-butyryl-1, 3-distearoyl glyceride, and mixture/combination thereof (See Col. 13, line 42; Col. 27, Example 5, 6, 8, 14-18). It’s noted 1, 3-dibutyryl-2-stearoyl glyceride read on instantly claimed other triglyceride recited in instant claim 14.
Wheeler teaches reduced calorie fat mixtures are prepared by inter- esterifying hydrogenated canola oil with tributyrin in the presence of 0.2 to 0.3% sodium methoxide (See Example 20, 21 and 28. ). Wheeler also teaches inter-esterifying safflower oil with tributyrin (See Example 31-32).
Regarding instant claimed method for treating overweight/obesity, Wheeler teaches correlation of calories ingested and animal body weight gain, and in-vivo test wherein low calorie triglycerides were administered to rats and weight gain were measured (See Col. 37, Example 26).
Regarding the percentage limitation recited in claims 8-9, 11-12 and 19-20, Wheeler teaches low calorie triglycerides generally contain 33 to 67 % short acid residues, up to 20% of unsaturated long fatty acid and the functional properties of triglyceride can be tuned/modified by selection of S and L groups and by the ratio of SSS, SLS, SSL, LLS, LSL components in the mixture (See Col. 8, line 15-16; Col 9, line 13 to Col. 10, line 44), For example, the percentage of LLS in the mixture can range from 0-40%, the percentage of SLS in the mixture can range from 15-85% (See Col. 6, lines 28-34; Col. 10, lines 24-35). Wheeler teaches butyryl-stearoyl glyceride mixture of LSS, SLS, LLS, LSL, comprising 56.4% SSL/SLS, 30% LSL/LLS (See Example 8, 14-18, 21; Col. 27, Col. 31, lines 9-10).
Regarding limitation of nutritional composition recited in claims 15-16, Wheeler teaches low-calorie triglyceride can be formulated into variety of food products, nutrient, etc.(See Col. 13, lines 15-35). Wheeler teaches medium chain triglycerides have been employed in premature infant formulas and in the treatment of several malabsorption syndromes (See Col. 4, lines 56-62)
Regarding limitation of carbohydrate source recited in claims 17-18, Wheeler teaches embodiments comprising low-calorie butyrate-containing triglyceride further comprising sugar /starch component, e.g. dextrose and the like in food (See Col. 23, lines 40- 56; Example 44-45). A skilled artisan would have known lactose is a commonly known sugar/carbohydrate.
Wheeler collectively teaches a method for reducing calories in food composition comprising low calorie triglycerides bearing butyrate moiety and long chain fatty acid moiety, whereas the low calorie triglyceride has dietary benefit for body weight control.
The difference of butyrate moiety containing triglyceride taught by Wheeler(e.g. Example 5, 8, etc.) with instant application is the saturated stearyl group (18: 0) compared with unsaturated oleoyl group (18:1). However, Wheeler also teaches inter-esterifying safflower oil with tributyrin (See Example 31-32). Wheeler teaches long chain fatty acid residue R can incorporate unsaturated acid moiety (e.g. oleic, linoleic, etc.) from non-hydrogenated high oleic sunflower oil (See Col. 8, line 54-55), wherein the low calorie triglyceride contain up to 20% unsaturated fatty acid residue(See Col. 12, line 34; claims 29, 31). Wheeler teaches oleic acid moiety provides advantageous property compared with saturated stearyl group , e.g. better absorption, lower melting point for formulation (See Col. 2, lines 16-20, 42-45).
Finley teaches triglyceride compositions comprising unsaturated long chain fatty acid moiety(e.g. oleic acid) and short chain acid (e.g. butyric acid) with reduced calorie for promoting weight loss (See abstract, [0012]-[0017]; claims 1-21).
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Finley teaches examples of unsaturated long chain fatty acids are oleic acid, linoleic acid and linolenic acid, and short chain fatty acids are selected from acetic acid, propionic acid, and butyric acid (See [0017], claim 2-10 and 14-20). Finley teaches triglyceride embodiment comprising oleoyl moiety and butyrate moiety (See claim 5, 10, 17 and 21) and preferred embodiment, 1, 3-dioleyl-2-butyrylglycerol (See [0017]. It’s noted 1,3-di(oleoyl)-2-butyroyl-glycerol is regioisomer of instantly claimed formula (6) which also reads on instantly claimed triglyceride having formula (7) recited in instant claim 10.
Finley collectively teaches the technical feature/benefit of employing oleic acid as long chain fatty acid in low calorie triglycerides, its role to reduce fat calories for weight loss and a preferred embodiment 1, 3-dioleyl-2-butyrylglycerol comprising two oleoyl moieties and butyrate moiety.
Klemann also teaches mixture of edible low calorie triglycerides comprising butyrate moiety and unsaturated long chain fatty moiety U (e.g. oleic acid) for use in weight control (See abstract, [0086], claims 1-7). Klemann teaches lipid triglyceride compositions/mixture comprising a variety combinations of triglycerides comprising short triglyceride moieties (S), medium triglyceride moieties (M), long unsaturated triglyceride moieties (U) and long saturated triglyceride moieties (L)(See [0025]-[0026], [0040]), such that the structured lipid component has the capacity to simultaneously provide dietary and other health benefits, e.g. calorie reduction, weight control (See [0001], [0027],[0038]). Klemann discloses short triglyceride moieties (S) derived from butyric acid, acetic acid, propionic acid or mixtures thereof, medium triglyceride moieties (M) derived from caproic acid, caprylic acid, capric acid, lauric acid, or mixtures thereof, and long unsaturated triglyceride moieties (U) present derived from palmitoleic acid, oleyl acid, vaccenic acid, linoleic acid, alpha-linolenic acid, gamma linolenic acid, gadoleic acid, arachidonic acid, eicosapentaenoic acid, erucic acid, docosahexaenoic acid, or mixtures thereof, (See [0027]).
Klemann teaches various combination of triglycerides USU, SSU, USS structures etc. comprising butyrate moiety (See 0025]. For example, Klemann teaches triglyceride composition comprising 12% of 1,3-di(oleoyl)-2-butyroyl-glycerol and 40% of 1-stearoyl-3-oleoyl-2-butyryl glycerol (See Example 1, [0086]). It’s noted 1,3-di(oleoyl)-2-butyroyl-glycerol is regio-isomer of instantly claimed formula (6) which also reads on instantly claimed triglyceride having formula (7) recited in instant claim 10. 1-stearoyl-3-oleoyl-2-butyryl glycerol is the regio-isomer of instantly claimed 1-stearoyl-2-oleoyl-3-butyrylglycerol recited in instant claim 14.
Regarding the limitation of carbohydrate/sugar limitation of new claims 17 and 18, Klemann also teaches food product comprising low calorie triglycerides further comprises starch component , sweetener, e.g. sugar, etc.(See [0079])
Klemann collectively teaches nutritional composition comprising mixture/combinations of low calorie triglyceride comprising butyrate moiety and oleoyl moiety, and amount/percentage thereof, having highly desirable dietary benefits for weight control.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of instant invention to modify the low-calorie triglycerides comprising butyrate moiety and stearyl moiety taught by Wheeler, with oleoyl moiety taught by Finley and Klemann, further explore fatty acid moiety combination and percentage thereof based on general knowledge of nutritional triglyceride, and arrive at the instant application with reasonable expectation of success. At the time the invention was made, it was already known that low-calorie triglyceride combination/mixture comprising butyrate moiety and stearyl moiety can be used for weight control as taught by Wheeler. Finley collectively teaches the technical feature/benefit of employing oleic acid as long chain fatty acid in low calorie triglycerides, its role to reduce fat calories for weight control and embodiment comprising two oleoyl moieties and butyrate moiety. Klemann also teaches low-calorie triglyceride comprising butyrate moiety and unsaturated long chain fatty moiety (e.g. oleoyl moiety) for weight control . Both Finley and Klemann teach 1,3-di(oleoyl)-2-butyroyl-glycerol, regioisomer of instant formula (6) and Klemann further teaches percentage of 1,3-di(oleoyl)-2-butyroyl-glycerol (12%).
A skilled artisan would be motivated to explore more low-calorie triglyceride by replacing the stearyl moiety of triglyceride taught by Wheeler with an oleoyl group as the long chain fatty acid because both Wheeler and Finley teach the advantage of unsaturated fatty acid over saturated fatty acid. Finley teaches diets high in saturated fat is associated with increased risk of heart disease and it’s desirable to provide reduced-fat triglyceride made primarily of unsaturated fatty acid([0006]). It’s well known that unsaturated fatty acid also provides other health benefit compared with saturated fatty acid. Where 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. MPEP 2144.05. The modification of triglycerides comprising stearyl moiety with oleoyl moiety based on combined teaching of prior art, together with exploration /optimization based on general knowledge of nutritional triglyceride, would provide alternative nutritional low-calorie triglyceride combination/mixture comprising butyrate moiety and oleoyl moiety, having lower melting point for easier formulation and better absorption/digestion for potential use in controlling calorie intake and weight control.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teaching of prior art and optimization based on general knowledge of nutritional triglyceride. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues independent claims 8 and 11 each recite, in part, wherein digestion of the composition generates butyrate in an amount effective for treating overweight and/or obesity in the individual through enhancement of energy expenditure and induction of mitochondrial function. None of the cited references disclose or suggest at least this limitation. Rather, Wheeler, Klemann, and Finley present triglycerides only as preventative measures to limit weight gain--rather than as treatments capable of reducing existing obesity (i.e., promoting fat loss). Wheeler, Klemann, and Finley do not teach or suggest achieving a direct therapeutic effect through enhancement of energy expenditure and induction of mitochondrial function. Further, the cited references are silent regarding digestion of the claimed composition generating butyrate (Remarks, page 10/11)
RESPONSE: Applicant’s argument is fully considered, but NOT persuasive. As explained in previous office action and elaborated above, instant claims are drawn to triglycerides composition per se , not butyrate that might be generated once digested that might be responsible for providing an effect relevant to weight control. The amended limitation drawn to mechanism/function of butyrate does not further limit the step of administering instant claimed triglyceride composition and does not necessarily contribute to the patentability of instant claimed method of treating obesity/overweight. The function/mechanism of instant claimed composition as low-calorie food to limit weight gain for treating obesity or by releasing butyrate associated with enhancement of energy expenditure and induction of mitochondrial function, are property of the compounds formula (5) and (6) ,which does not further limit the step of administering the triglycerides composition. It’s common knowledge that low-calorie food are generally associated with weight loss/reducing obesity as taught by Finley. Even if prior art is silent about the digestating profile, by practicing the method made obvious by the prior art of administering butyrate moiety containing triglyceride to the obese or overweight subjects in need of reducing weight , one would also be practicing weight control by release of butyrate in the intestine following digestion.
As noted before, instant claimed formula (6) is an isomer of Finley preferred compound and a skilled artisan would reasonably expect similar activity/function for the isomers. Wheeler and Klemann not only teach the butyrate containing triglycerides as low calorie alternative for weight management, Wheeler, Klemann and their incorporated reference also teach the digestibility/ metabolism of tributyrin and potential mechanism of tributyrin use for weight control. As Liu (2018) teaches, variety of different mechanisms have been proposed to explain the effects of butyrate on alleviating obesity. As MPEP 2112.I.states: "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)”.
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 8, 9, 11, 12, 15-16 and 19- 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12667552 ( granted on 06/30/2026, corresponding US application 17/413,991), in view of Wheeler et al.(US 5662953, Applicant’s IDS dated 11/17/2021)(newly reapplied as necessitated by amendment).
Reference claims are directed to a method for prevention / treatment of dehydration comprising administering combination of butyrate containing triglycerides. Reference claim 5 recites composition comprising formula (1) and formula (2) with similar weight ratio limitation as instant claims. Reference claim 8 recites R1, R2, R3 is oleic acid read on instant claimed formula (5) and (6).
Reference claim 3 recites nutritional composition, infant formula, a follow-on formula or a dietary supplement that read on instant claims 15and 16.
The reference claims do not recite a method of treating overweight/obesity. However, by administering compounds of the reference claims having the same formula (5) and (6) as instant claims, one will also be practicing instantly claimed method of managing weight, since the same triglyceride composition comprising formula(5) and (6) are being administered.
As elaborated in preceding 103 rejection, Wheeler collectively teaches a method for reducing calories in food composition comprising low calorie triglycerides bearing butyrate moiety and long chain fatty acid moiety, whereas the low calorie triglyceride has dietary benefit for body weight control. It would have been obvious for one of ordinary skilled in the art to produce the claimed invention with reasonable expectation of success, based on combined teaching of reference claims, Wheeler and optimization based on general knowledge of nutritional triglyceride.
Claims 8, 9, 11, 12, 15, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. patent No. 12661334 (granted on 06/23/2026, corresponding US application No. 17/595,516), in view of Wheeler et al.(US 5662953, Applicant’s IDS dated 11/17/2021) (newly reapplied as necessitated by amendment).
Reference claims are directed to a method for prevention and/or treatment of non- alcoholic fatty liver disease, comprising administering combination of butyrate containing triglycerides. Reference claims 1 and 4 explicitly teach composition comprising instantly claimed formula (5) and formula (6) with similar weight ratio limitation as instant claims. Reference claim 7 recites nutritional composition that read on instant claims 15.
The reference claims do not recite a method of treating overweight/obesity. The rationale of combining reference claims and Wheeler for a method of treating overweight/obesity is similar as elaborated in preceding nonstatutory double patenting rejections.
Claims 8, 9, 11, 12, and 14-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending U.S. patent No. 12648923 (granted on 06/09/2026, corresponding to application No. 17/756,871), in view of Wheeler et al.(US 5662953, Applicant’s IDS dated 11/17/2021) (newly reapplied as necessitated by amendment).
Reference claims are directed to a method for promoting immune response and/or preventing and/or treating bacterial and/or viral infections , comprising administering combination of butyrate containing triglycerides. Reference claims 8-9 and 11-12 explicitly teaches composition comprising instantly claimed formula (5) and formula (6) with similar weight ratio limitation as instant claims. Reference claim 14 recites butyrate containing triglycerides that read on instant claim 14. Reference claim 15-16 recite nutritional composition that read on instant claims 15-16.
The reference claims do not recite a method of treating overweight/obesity. However, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. The rationale of combining reference claims and Wheeler for a method of treating overweight/obesity is similar as elaborated in preceding nonstatutory double patenting rejections.
Claims 8, 9, 11, 12, 15-16, and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-4, 11-13, 25-27 of copending Application No. 17/044,684 (US 20210038554 A1), in view of Wheeler et al.(US 5662953, Applicant’s IDS dated 11/17/2021) (newly reapplied as necessitated by amendment).
Reference claims are directed to a method for providing a source of butyrate comprising administering combination of butyrate containing triglycerides wherein R1, R2, and R3 are independently a long chain fatty acid having between 16 and 20 carbons, wherein the combination is present in a composition that comprises the first compound having formula (1) in an amount of at least 10% by weight of total butyrate moiety containing triglycerides in the composition, and the second compound having formula (2) in an amount of at least 10% by weight of the total butyrate moiety containing triglycerides in the composition. Reference claims 25-26 recite nutritional composition, infant formula, a follow-on formula or a dietary supplement that read on instant claims 15 and 16.
The reference claims do not recite a method of treating overweight/obesity. However, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
As elaborated in preceding 103 rejection, Wheeler collectively teaches a method for reducing calories in food composition comprising low calorie triglycerides bearing butyrate moiety and long chain fatty acid moiety, whereas the low calorie triglyceride has dietary benefit for body weight control. It would have been obvious for one of ordinary skilled in the art to produce the claimed invention with reasonable expectation of success, based on combined teaching of reference claims, Wheeler and optimization based on general knowledge of nutritional triglyceride,.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 8, 9, 11, 12, 14-16 and 19-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-10, 13-14,16, 18-19 of copending U.S. Patent Application No. 17/595,451(reference application), in view of Wheeler et al.(US 5662953, Applicant’s IDS dated 11/17/2021). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented(newly reapplied as necessitated by amendment).
Reference claims are directed to a method for reducing frequency and/or occurrence and/or severity and/or duration or treatment of metabolic disorders, comprising administering combination of butyrate containing triglycerides. Reference claims 9 and 10, explicitly teaches composition comprising instantly claimed formula (5) and formula (6) with similar weight ratio limitation as instant claims 8-9 and 11-12. Reference claim 16 recites butyrate containing triglycerides that read on instant claim 14. Reference claim 18 and 19 recites nutritional composition, infant formula, a follow-on formula or a dietary supplement that read on instant claims 15 and 16.
The reference claims do not recite a method of treating overweight/obesity. The rationale of combining reference claims and Wheeler for a method of treating overweight/obesity is similar as elaborated in preceding nonstatutory double patenting rejections.
Claims 8, 9, 11, 12 and 14-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending U.S. Patent Application No. 17/756,872 (reference application), in view of Wheeler et al.(US 5662953, Applicant’s IDS dated 11/17/2021). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented(newly reapplied as necessitated by amendment).
Reference claims are directed to a method for preventing and/or treating gastrointestinal infections , comprising administering combination of butyrate containing triglycerides. Reference claims 8-9, and 11-12 explicitly teaches composition comprising instantly claimed formula (5) and formula (6) with similar weight ratio limitation as instant claims 8-9and 11-12. Reference claim 14 recites butyrate containing triglycerides that read on instant claim 14. Reference claims 15 and 16 recite nutritional composition that read on instant claims 15 and 16.
The reference claims do not recite a method of treating overweight/obesity. However, products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. The rationale of combining reference claims and Wheeler for a method of treating overweight/obesity is similar as elaborated in preceding nonstatutory double patenting rejections.
Conclusion
No claims are 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.
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/L.M./Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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