DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The present application is a DIV of 17/420,411 filed on 07/02/2021, which is a 371 of PCT/US2020/013595 filed on 01/15/2020, which claims the benefit under 35 U.S.C 119 (e) to U.S. Provisional Application No. 62/792,650 filed on 01/15/2019. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C 119 (e) or under 35 U.S.C 120, 121, or 365 (c ) is acknowledged.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 11/04/2024 has been considered.
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claim 1, regarding the scope of “treating an autoimmune disease in a subject”, it is noted that the instant specification does not define what constitutes “treating”. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. The Britannica Dictionary defines “treat/treating” as to deal with (a disease, infection, etc.) in order to make someone feel better or become healthy again (see The Britannica Dictionary, definitions 4a and 4b, at https://www.britannica.com/dictionary/treat, pp. 1-2, accessed on 02/27/2026). As such, the Examiner is interpreting the scope of “treating” an autoimmune disease in a subject as dealing with an autoimmune disease by administering a composition comprising a glycated α-lactalbumin and a glycated ß -lactoglobulin or a combination thereof in order to make the subject feel better or become healthy again.
Similarly, regarding the scope of “preventing an autoimmune disease in a subject”, it is noted that the instant specification does not define what constitutes “preventing”. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. The Britannica Dictionary defines “prevent/preventing” as to stop (something) from happening or existing (see The Britannica Dictionary at https://www.britannica.com/dictionary/prevent, pg. 1, accessed on 02/27/2026). As such, the Examiner is interpreting the scope of “preventing” an autoimmune disease in a subject as to stop the autoimmune disease from happening or existing (i.e., as in 100% prevention), by administering a composition comprising a glycated α-lactalbumin and a glycated ß -lactoglobulin or a combination thereof.
Also for claim 1, regarding the scope of “glycated”, the instant specification does not define what constitutes “glycated”. Pursuant to MPEP 2111.01, under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the time of the invention. New England Biolabs describes “glycation” as a random mechanism (i.e., non-enzymatic), that occurs in the bloodstream where the reducing (reactive) ends of free sugars (i.e., glucose, fructose, galactose) covalently attach to proteins, creating glycated products (see New England Biolabs at https://www.neb.com/en/faqs/what-is-the-difference-between-glycosylation-and-glycation?srsltid=AfmBOorjsJDbSQVE2ierp-xnGCnLolI3IC9cyG4ZMupqIHRwa8UHXQSE#:~:text=The%20reducing%20(reactive)%20ends%20of,related%20to%20several%20disease%20processes., accessed on 3/4/2026). Therefore, the Examiner is interpreting the scope “a glycated α-lactalbumin” and “a glycated ß-lactoglobulin” as proteins (i.e., α-lactalbumin and ß-lactoglobulin) with an undetermined/unspecified number of sugar molecules (e.g., glucose, fructose, galactose, etc.) covalently attached thereto.
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.
1. Claim 1-5, 7-8, 11-17 and 19-20 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that 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, 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.
Claim 1 is drawn to a method for treating or preventing an autoimmune disease in a subject, comprising administering to the subject a composition comprising a glycated α-lactalbumin, a glycated β-lactoglobulin, or a combination thereof. The scope of the claimed method encompasses administering a composition comprising a glycated α-lactalbumin, a glycated ß-lactoglobulin or a combination thereof. As discussed in the “Claimed Interpretation” section above, glycated α-lactalbumin and glycated ß-lactoglobulin are being interpreted as α-lactalbumin and ß-lactoglobulin having an undetermined/unspecified number of sugar (e.g., glucose, fructose, galactose, etc.) molecules covalently attached thereto molecules. Thus, independent claim 1 and dependent claims 2-5, 7-8, 11-17 and 19-20 encompass a vast array of glycated α-lactalbumin and glycated β-lactoglobulin or combination thereof without a necessary core structure or sequence that exhibits the function of treating or preventing an autoimmune disease in a subject. In other words, claims 1-5, 7-8, 11-17 and 19-20 fail to describe the glycation degree of the glycated α-lactalbumin and glycated β-lactoglobulin.
Applicants reduce to practice two examples, wherein glycated whey proteins protected non-obese diabetic mice (NOD) against Type 1 Diabetes by increasing anti-inflammatory responses and decreasing autoreactivity to self-antigens (see instant specification, Example 1, pg. 17); and wherein chronic oral exposure to glycated whey proteins increases survival of aged male NOD mice with autoimmune prostatitis by regulating gut microbiome and anti-inflammatory responses (see instant specification, Example 2, pg. 31). The specification teaches that a solution containing whey protein isolate (WPI) and glucose was freeze-dried, and the powders were further incubated in sealed desiccator maintained at aw 0.53 and 55 °C for different durations; glycation markers were quantitated and the 8 h samples were determined as early glycation products (EGPs) (see instant specification, pg. 17, para[0081]). Consequently, after 8 h reaction, no original forms of α-La (i.e., α-lactalbumin) or ß-Lg (i.e., ß-lactoglobulin) remained (see instant specification, pg. 22, para[0105] and Fig. 1 B, lower panel). All the α-La reacted with 3-11 glucoses, with the 6-glucose attached α-La being the most abundant and the average degree of substitution per protein (DSP) of 7.2 (see instant specification, pg. 22, para[0105]). Both variants of ß-Lg were attached by 5-15 glucoses; the 10-glucose attached form was the most abundant and the average DSP was 9.7 for both variants (see instant specification, pg. 22, para[0105]). As such, the specification only teaches treating two autoimmune diseases (i.e., T1D and autoimmune prostatitis) with α-La glycated/reacted with 3-11 glucoses and with ß-Lg glycated/reacted with 5-15 glucoses.
The written description may be met by provided a representative number of species of the genus in the specification and/or in light of the state of the art. With regard to the state of the art, WO 00/18249 International Publication Date: April 6, 2000 (herein after “Boland”) describes a process for controlling Maillard-type glycation of whey proteins and products with enhanced functional properties (see Title); wherein different levels of glycated whey proteins were obtained due to different processing histories of the samples (see Boland, pg. 10, lines 1-6 and Table 1). Similarly, Chen et al., report glucose glycation of α-Lactalbumin and ß-Lactoglobulin in glycerol solution (see Chen et al., J. Agric. Food Chem. 2018, 66, 10558-10566, (cited in the IDS filed on 11/04/2024) at pg. 1, Title). Chen et al. also teach the average degree of substitution per protein (DS) of α-La and ß-Lg in different glycation conditions (see Chen et al., pg. 10561, right column, Table 2). Where on average, each α-lactalbumin molecule was attached by three to four glucose molecules after heating for 18, 72, and 96 h at a water activity of 0.044, 0.162, and 0.247, respectively (Chen et al., pg. 10561, right column, last paragraph). The case in β-lactoglobulin was 5 to 6 glucose molecules added onto the protein after heating for 18, 48, and 72 h (Chen et al., pg. 10561, right column, last paragraph). Chen et al. add that the α-lactalbumin and β-lactoglobulin with 3 and 5 glucose molecules showed as being the most abundant glycated form and that compared with glycation in a solid matrix, the glycation rate in glycerol was lower and most likely limited by the concentration of reactants (see Chen et al., pg. 10562, left column, first paragraph). As previously reported, it took 8 h to obtain glucose-glycated β-lactoglobulin of an average DSP at 5 in a solid-matrix-based system (45 °C, water activity at 0.53) (see Chen et al., pg. 10562, left column, first paragraph). As such, the state of the prior art demonstrates that the amount of sugar molecules attached to the protein of interest, i.e., α-La and ß-Lg, is unpredictable and varies according to the reaction conditions.
Therefore it would be difficult for a skilled artisan to envision the function of the claimed method for treating or preventing the whole genus of autoimmune diseases and/or to predict what degree of substitution per protein/glycation degree would be covered by the claimed glycated α-La and glycated ß-Lg. Thus, a representative number of species of autoimmune diseases and a representative number of species of glycated α-La and glycated ß-Lg have not been provided.
Claims 6, 9-10 and 18 are excluded from this rejection, however, claims 1-5, 7-8, 11-17 and 19-20 do not meet the written description requirement.
2. Claims 1 and 5-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating type 1 diabetes and autoimmune prostatitis, by administering to the subject a composition comprising α-La reacted with 3-11 glucoses with the 6-glucose attached α-La being the most abundant and the average DSP of 7.2; and variants of ß-Lg (i.e., ß-Lg variant B and ß-Lg variant A) reacted with 5-15 glucoses with the 10-glucose attached form as the most abundant and the average DSP of 9.7 for both variants; does not reasonably provide enablement for preventing an autoimmune disease in a subject comprising administering to the subject a composition comprising a glycated α-La, a glycated ß-Lg, or a combination thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining
whether there is sufficient evidence to support a determination that a disclosure does not satisfy
the enablement requirement and whether any experimentation is ‘undue’.” These factors
include, but are not limited to:
1.The breadth of the claims;
2.The nature of the invention;
3.The state of the prior art;
4.The level of skill in the art;
5.The level of predictability in the art;
6.The amount of direction provided by the inventor;
7.The presence or absence of working examples;
8.The quantity of experimentation needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
The eight In re Wands factors are applied to claims 1 and 5-20 as follows:
Breadth of the Claims and the Nature of the Invention
Claims 1 and 5-20 are drawn to a “method for treating or preventing an autoimmune disease in a subject …” The Applicant claims prevention of an autoimmune disease by administering to the subject a composition comprising a glycated α-lactalbumin, a glycated ß-lactoglobulin, or a combination thereof. As discussed in the Claim Interpretation (see above), the claimed prevention includes 100% prevention. Details disclosed in the specification do not show that an autoimmune disease, can be prevented.
Instead, the instant specification teaches that when early glycation products were administered to two T1D mice models (MLD-STZ model and Non-Obese Diabetic (NOD) model), one or more symptoms of T1D were reduced or ameliorated. For instance, the specification at pg. 26, para[0119] recites that NOD males and females showed decreased and stabilized non-fasting blood glucose levels (BGLs), increased glucose metabolism during glucose tolerance test (GTT) and increased insulin sensitivity during insulin tolerance test (ITT), which were accompanied with reduced pancreatic immune infiltrates. The specification also discusses that in the STZ-induced T1D model, which is much less immune-dependent, the protective effect of EGPs against T1D diminished, thus suggesting that early glycation products were likely to exert their effect through modulating the immunity (see pg. 26, para[0119-0120]).
With respect to the second autoimmune disease reduced to practice (i.e., autoimmune prostatitis), the specification teaches that chronic exposure to glycated whey protein alleviated autoimmune prostatitis and increased the survival rate in aged NOD male mice, thus extending the potential application of EGPs from T1D to a broader spectrum of autoimmune diseases (see pg. 40, para[0167]). Since exposure to EGPs increases the survival rate and moderately reduces the prostatic inflammation in NOD mice with autoimmune prostatitis, alters the systemic immunity and modulate gut microbiome (see pg. 34, para[0145, 0149, 0153]). However, Applicants failed to provide evidence in the specification that a composition comprising a glycated α-Lactalbumin, a glycated ß-lactoglobulin, or a combination thereof can 100% prevent an autoimmune disease in a subject. Accordingly, claims 1 and 5-20 are unduly broad with respect to preventing an autoimmune disease.
The State of the Prior Art
Pertaining to claims 1 and 5-20, administering a glycated α-lactalbumin, a glycated ß-lactoglobulin or a combination thereof is not the standard of care for treating or preventing an autoimmune disease. The prior art teaches that although there are treatments to slow down the progression of autoimmune diseases, there is currently no cure (see Institut Pasteur, “Autoimmune diseases: when our defenses turn against us” in The Research Journal, 04/03/2018, retrieved from https://www.pasteur.fr/en/home/research-journal/reports/autoimmune-diseases-when-our-defenses-turn-against-us on 3/04/2026, pp. 1-16, at pg. 2). Instead most autoimmune diseases are treated by methods to control and reduce the immune and inflammatory responses (see Institut Pasteur, pg. 10, second paragraph). For instance, corticosteroids, known for their anti-inflammatory properties, are the standard therapy but can have harmful long-term effects. Immunosuppressive drugs such as cyclosporine, also used to prevent organ rejection in transplant patients, may be administered. But by suppressing the autoimmune reaction, they also reduce the body's ability to defend against microorganisms (bacteria, viruses, etc.) or to eliminate cancer cells. This risk of developing infection or cancer means that patients need to be carefully monitored (see Institut Pasteur, pg. 10, second paragraph). Other methods of treatment include lifestyle and diet changes which can help improve the condition (see University of Kansas Health Systems, “6 Diet Tips for Healing from Autoimmune Disease”, 2017retrieved from https://www.kansashealthsystem.com/news-room/blog/2017/02/autoimmune-disease-diet, on 3/4/2026, pp. 1-2). Furthermore, it is noted that there is no current prior
art that teaches administering a glycated α-lactalbumin, a glycated ß-lactoglobulin or a combination thereof for preventing an autoimmune disease in a subject. Accordingly, the prior art demonstrates that the scope of claims 1 and 5-20 encompass preventing an autoimmune disease that would require undue experimentation given that to date, autoimmune diseases cannot be prevented.
The Level of Skill in the Art
Practitioners in this art (medical clinicians, pharmacists, doctors and/or pharmaceutical
chemists) would presumably be highly skilled in the art for prevention of an autoimmune disease in a subject.
The Level of Predictability in the Art
The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). In the instant case, Applicants do not demonstrate that a composition comprising a glycated α-lactalbumin, a glycated ß-lactoglobulin or a combination thereof administered to a subject is an effective method for preventing an autoimmune disease. Rather, Applicants only demonstrate that early glycation products (i.e., α-La glycated/reacted with 3-11 glucoses and with ß-Lg glycated/reacted with 5-15 glucoses, averaging 6 glucose moieties per glycated to α-La and 10 glucose moieties per glycated ß-Lg) administered to mice is capable of ameliorating/reducing the symptoms of T1D and autoimmune prostatitis in NOD mice, but fail to demonstrate that a composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof administered to a subject prevents (i.e., 100% prevention) an autoimmune disease in a subject. Applicants appear to rely on the assumption that by providing evidence early glycation products (i.e., α-La glycated/reacted with 3-11 glucoses and with ß-Lg glycated/reacted with 5-15 glucoses, averaging 6 glucose moieties per glycated to α-La and 10 glucose moieties per glycated ß-Lg) reduce disease symptoms in mice would exhibit similar intended results for the prevention of an autoimmune disease in a subject. However, such an assumption cannot be made because there is no indication that a composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof would exhibit such results. Additionally, since the Specification fails to demonstrate any data or evidence that the claimed composition prevents an autoimmune disease in a subject, there would be no way of determining without undue experimentation whether the claimed method comprising administering a composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof exhibits such a desired result. Without more experimentation demonstrating the efficacy of the claimed method for prevention of an autoimmune disease, the level of unpredictability remains high. Therefore, it is unpredictable that the claimed composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof will prevent an autoimmune disease in a subject.
The Amount of Direction Provided by the Inventor and The Presence or Absence of Working Examples
The specification does not enable any person skilled in the art to which it pertains (i.e. administering a composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof to a subject in order to prevent an autoimmune disease) to make and/or use the invention commensurate in scope with the claims. There is a lack of adequate guidance from the specification or prior art with regard to the actual prevention of an autoimmune disease by administering to a subject the claimed composition. Applicants fail to provide the guidance and information required to ascertain where the claimed composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof will be effective against preventing an autoimmune disease without resorting to undue experimentation.
Absent a reasonable a priori expectation of success for using the claimed composition to prevent an autoimmune disease, one skilled in the art would have to extensively test the efficacy of a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof in vitro and in vivo. Since each prospective embodiment, and indeed future embodiments as the art progresses, would have to be empirically tested, and those which initially failed tested further, an undue amount of experimentation would be required to practice the invention as it is claimed in its current scope because the specification provides inadequate guidance to do otherwise.
The amount of direction or guidance presented in the specification is very limited. The
Specification discloses two working examples where a composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof administered to mice demonstrated improved disease activity based on a reduction in bodyweight loss, blood glucose levels and/or measurement of key cytokines involved in inflammation and immune regulation (see Specification, Example 1 and 2). For Example 1, the data indicated that oral intake of whey protein isolates (WPI) derived EGPs delayed the T1D onset in NOD females through modulating the immunity, and that EGP consumption reduced CD8+ T cells and IAAs, and increased IL-10, CD4+CD25+ regulatory T cells and the anti-inflammatory responses by shifting M2/M1 balance toward M2 (see instant specification, pg. 28, para[0124]). Therefore although delayed, the occurrence of the autoimmune disease (i.e., T1D) was not 100% prevented. Similarly for Example 2, the data revealed that chronic exposure to glycated whey protein alleviated autoimmune prostatitis and increased survival rate in aged NOD male mice, however the data does not translate to 100% prevention of autoimmune prostatitis. Therefore, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation.
The Quantity of Experimentation Needed
In light of the unpredictability surrounding the claimed subject matter, the breadth of the claimed invention, and the lack of adequate guidance, one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation. To practice the presently claimed invention, one would have to gather additional data and perform experimentation to determine whether a composition comprising a glycated α-Lactalbumin, a glycated ß-Lactoglobulin or a combination thereof is capable of preventing an autoimmune disease in a subject. Additional experimentation may include, but is not limited to, performing additional analysis in animal models as well as performing clinical trials in subjects.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
MPEP §2164.01(a), 4th paragraph, provides that, “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 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1 and 5-20, in view of Applicants’ entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above; it is concluded that the practice of the invention as claimed in claims 1 and 5-20, would not be enabled by the written disclosure excluding that of treating T1D and autoimmune prostatitis in aged male NOD mice by administering the claimed composition, where treating comprises alleviating or reducing the progress of the autoimmune disease of interest. Therefore, claims 1 and 5-20 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to administer the claimed composition to a subject in order to prevent an autoimmune disease.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
3. Claims 1-5 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0119614 A1 Pub. Date: May 13, 2010 (herein after “Juneau”) in view of Chen et al., Mol. Nutr. Food Res. 2018, vol. 62, article 1700641, pp. 1-9 [first published 10/30/2017] (cited in the IDS filed on 11/04/2024) (herein after “Chen 2017”), as evidenced by Toro-Sierra et al., Food Bioprocess Technol. 2013, vol. 6, pp. 1032-1043 (cited in the IDS filed on 11/04/2024) (herein after “Toro-Sierra”).
Regarding claim 1, Juneau teaches a composition used in the prophylaxis and treatment of psoriasis and other autoimmune inflammatory disorders (see Juneau, abstract). Juneau adds that for prophylaxis, the composition is administered to a patient diagnosed with psoriasis, and prone to frequent relapse, in order to decrease manifestations of the disease in frequency and strength. Treatment in the manifest stage leads to its curtailment and to the alleviation of the symptoms (see pg. 4, para[0077]). Juneau’s composition may comprise TGF-ß1, TGF-ß2 and dairy derived proteins comprising a large proportion of ß-lactoglobulin (see Juneau, abstract). Juneau adds that the dairy-derived proteins may be comprised, for example but not limited to, of between 30 to 85% (w/w) of ß-lactoglobulin, preferably between 50 and 70% and most preferably at least 60%; and between 0 and 25% (w/w) of α-lactalbumin (see pg. 4 para[0068]). Furthermore, Juneau tested the composition on TNBS-Induced Inflammation in Healthy rats in an inflammatory bowel disease rat model (see pg. 8, para[0111]). Juneau reported that TNBS injection (the stressor) increased macroscopic scores of inflammation in both groups (i.e., Group 2: TNBS stressed group and Group 3: composition treated group) indicating the presence of inflammation and edema (see pg. 9, para[0127]). However, the increase was significantly inferior (P<0.05) in animals treated with the composition (1x) than in TNBS-treated animals (see pg. 6, para[0127] and FIG. 6 and FIG. 7). Thereby Juneau’s invention reads on a method for treating or preventing an autoimmune disease in a subject as, administering a comprising a composition comprising α-lactalbumin, ß-Lactoglobulin or a combination thereof, recited in instant claim 1. However Juneau does not expressly teach wherein the α-Lactalbumin and ß-Lactoglobulin or combination thereof are glycated as recited.
Chen 2017 teaches that dietary glycation products regulate immune homeostasis (see Chen 2017, pg. 1, Title). Chen 2017 hypothesized that dietary glycation products of early and advanced stages could differentially regulate immune homeostasis (see pg. 2, left column, first full paragraph). The hypothesis was tested by establishing two glycation systems (glycine–glucose, and whey protein isolate (WPI)–glucose) which produced glycation products at different stages; the glycated products where then used to treat human macrophages (phorbol 12-myristate 13-acetate (PMA)-differentiated U937 cells) (see pg. 2, left column, first full paragraph). As evidenced by Toro-Sierra, the protein fractions α-lactalbumin (α-La) and β- lactoglobulin (β Lg) represent almost 70% of the protein concentration in whey and are present in a mixed form with a ratio of approximately 20:80 (See Toro-Sierra, pg. 1032, right column, paragraph 1). As such the system taught by Chen 2017 comprising WPI and glucose, constitutes a composition comprising glycated α-lactalbumin and glycated β- lactoglobulin.
Chen 2017 also teaches determining the glycation stage in both systems (i.e., glycine–glucose, and WPI–glucose) and that the Maillard reaction progression was monitored by quantitating five markers as depicted in Fig. 1 (see pg. 3, left column last paragraph, Fig. 1). Based on the glycation stage of the products obtained with the two systems, the 8-h samples of glycine–glucose and WPI–glucose systems were used as representative early glycation product (EGP) samples (see pg. 4, right column, first full paragraph). The glycation products of early and advanced stages affected the cytokine secretion by macrophages in different directions, which suggested their potential roles in regulating immune homeostasis (see pg. 5, right column last paragraph). EGPs exerted their effects through modulating cytokines mainly in the following four aspects: (1) activating other immune cells, (2) EGPs were immunosuppressive; (3) EGPs modulated inflammation, (4) EGPs altered the host defense (see pg. 5 last paragraph and pg. 7, left column). Chen 2017 mapped the biological functions of EGPs by functional enrichment analysis as depicted in Fig. 4 (see pg. 4, right column, first full paragraph). Chen 2017 concluded that glycation products regulate immune homeostasis at least in part through modulation of macrophage to secret cytokines, and do so in a glycation-stage-dependent manner and that EGPs increased the production of cytokines in macrophages (see pg. 8, left column, second paragraph). Chen 2017 add that EGPs are immunomodulatory and their effect is likely disease specific (see pg. 8, left column, second paragraph).
From the teachings of the references, the Examiner recognizes that it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the α-lactalbumin and the ß-lactoglobulin proteins in Juneau’s composition with glycated whey proteins (i.e., glycated α-lactalbumin and glycated ß-lactoglobulin) in order to arrive at the claimed method of treating or preventing an autoimmune disease in a subject, comprising administering to the subject a composition comprising a glycated α-lactalbumin, a glycated ß-lactoglobulin, or a combination thereof. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because it was known reaction of whey protein isolate (WPI) with glucose under controlled settings yields early glycation products (EGP); because WPI derived EGP were known to exerted their effects through modulating cytokines mainly in the following four aspects: (1) activating other immune cells, (2) EGPs were immunosuppressive; (3) EGPs modulated inflammation, (4) EGPs altered the host defense as taught by Chen. One of ordinary skill in the art would have had a reasonable expectation of success given that Juneau’s composition comprised dairy derived proteins between 0 and 25% (w/w) α-lactalbumin, and between 30 to 85% (w/w) ß-lactoglobulin; and given that Juneau’s composition decreases manifestations in frequency and strength of an autoimmune inflammatory disorder or disease as evidenced by the results obtained with an inflammatory bowel disease rat model. Therefore, substituting α-lactalbumin and ß-lactoglobulin in Juneau’s composition with glycated WPI (i.e., glycated α-lactalbumin and glycated ß-lactoglobulin) would support a method for treating or preventing an autoimmune disease in a subject comprising administering to the subject a composition comprising a glycated α-lactalbumin and a glycated ß-lactoglobulin, or a combination thereof; by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or the use of a known technique to improve similar devises (methods, or products)in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant to KSR.
Regarding claims 2-5, as previously mentioned, Juneau teaches using the composition in the prophylaxis and treatment of psoriasis and other autoimmune inflammatory disorders (see Juneau, abstract). As such, other autoimmune inflammatory disorders encompass type 1 diabetes, or gestational diabetes and autoimmune prostatitis as, as recited in instant claims 2-5.
Regarding claims 14-17, Juneau teaches that the compounds of the composition can preferably be administered orally in the form of granules, capsules, pills, tablets, film-coated tablets, sugar-coated tablets (see pg. 5, para[0090]). Preparations to be administered orally can contain one or more additives such as sweeteners, aromatizing agents, colorants and preservatives (see pg. 5, para[0090]). Tablets can contain the active compound mixed with customary pharmaceutically tolerable auxiliaries, for example inert diluents such as calcium carbonate, sodium carbonate, lactose and talc, granulating agents and agents (see pg. 5, para[0090]). Apart from the excipients mentioned, tablets, of course, can also contain additives, such as sodium citrate, calcium carbonate and dicalcium phosphate together with various additives, such as starch, preferably potato starch, gelatin and the like (see pg. 6, para[0093]). As such, Juneau’s teachings read on the claim limitations recited in instant claims 14-16, wherein the composition further comprises a nutraceutically acceptable excipient; wherein the composition is in a solid unit dose form; wherein the solid unit dose form comprises an enteric coating; and wherein the solid unit dose form comprises tablets, beads, or granules.
Accordingly, the combined teachings of Juneau and Chen 2017 are suggestive of the claim limitations recited in instant claims 1-5 and 14-17.
4. Claims 1, 6-13 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0119614 A1 Pub. Date: May 13, 2010 (herein after “Juneau”) in view of Chen et al., Mol. Nutr. Food Res. 2018, vol. 62, article 1700641, pp. 1-9 [first published 10/30/2017] (cited in the IDS filed on 11/04/2024) (herein after “Chen 2017”), as evidenced by Toro-Sierra et al., Food Bioprocess Technol. 2013, vol. 6, pp. 1032-1043 (cited in the IDS filed on 11/04/2024) (herein after “Toro-Sierra”) for claim 1; and in further view of Chen et al. J. Agric. Food Chem. 2018, vol. 66, pp. 10558-10566 (cited in the IDS filed on 11/04/2024) (herein after “Chen 2018”); Deng et al., Food Hydrocolloids. 2017, vol. 69, pp. 210-219 (cited in the IDS filed on 11/04/2024) (herein after “Deng”); Chen et al., J. Agric. Food Chem. 2012, vol. 60, pp. 10674-10682 (cited in the IDS filed on 11/04/2024) (herein after “Chen 2012”) for claims 6-13 and 18-20 herewith.
Regarding claim 1, see discussion of Juneau and Chen 2017 above.
Regarding claims 6 and 18, Chen 2018 teaches the glucose glycation of α-lactalbumin and ß-lactoglobulin at 50°C in a glycerol-based liquid system (see Chen 2018, pg. 10558, abstract). Chen 2018 teaches that whey proteins including α-lactalbumin and ß-lactoglobulin were used, and that glycerol was used as the solvent matrix of glycation which controls the water activity in the system (see Chen 2018, pg. 10559, left column, paragraph 3). Chen 2018 adds that the glycation in a glycerol-matrix-based system was studied with respect to the reaction extent and site specificity influenced by the water activity and solvent matrix and that the glycation sites of the two proteins were identified by mass spectrometry (see Chen 2018, pg. 10559, left column, paragraph 3).
Chen 2018 describes that the glycated proteins were prepared by suspending protein powder in 30-100% glycerol solutions with a concentration of α-lactalbumin and ß-lactoglobulin at 0.77 and 0.63 mM, respectively (see Chen 2018, pg. 10559, paragraph 2), thereby constituting a composition comprising glycated α-lactalbumin and ß-lactoglobulin. The protein-glycerol solutions and the glycerol solutions without glucose were mixed in the same way and considered as heated controls (see Chen 2018, pg. 10559, paragraph 3). The samples and heated controls were incubated at 50 °C for 12, 24, 48, 72, and 96 h using a water bath; to stop the reaction, water was added with a final weight reaching 2.5 times that of each sample (see Chen 2018, pg. 10559, paragraph 3). The glycation extent was charted by the weighted average degree of substitution per protein (DSP), and by UPLC-ESI MS (ultra-high-performance liquid chromatography-electrospray ionization-mass spectrometry) instrument (see Chen 2018, pg. 10560, left column, paragraph 1). The glycation extent between protein (α-lactalbumin and ß-lactoglobulin) and glucose in glycerol solutions was determined using the OPA method by monitoring the free amino groups over time (see Chen 2018, pg. 10560, left column, paragraph 7). Chen 2018 teaches that on average, each α-lactalbumin molecule was attached by three to four glucose molecules after heating for 18, 72 and 96 h (See Chen, pg. 10561, right column, paragraph 4); and in the case of ß-lactoglobulin, 5-6 glucose molecules were added onto the protein after heating for 18, 48, and 72 h (see Chen 2018, pg. 10561, paragraph 4), thereby constituting a specific number of glucose moieties (i.e., 3 to 4) of α-lactalbumin that fall within the claimed range of 1 to 12 glucose moieties; and a specific number of glucose moieties (i.e., 5-6) of ß-lactoglobulin that fall within the claimed range of 1-16 glucose moieties. As such, Chen 2018 discloses a specific embodiment of a composition comprising α-LA with 3-4 glucose moieties and ß-LG with 5-6 glucose moieties; thereby corresponding to the claimed glycated α-lactalbumin having 1-12 glucose moieties, and the glycated ß-lactoglobulin having 1-16 glucose moieties, as recited in instant claim 6.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to to substitute the α-lactalbumin and the ß-lactoglobulin proteins in Juneau’s composition with the glycated α-Lactalbumin and ß-Lactoglobulin of Chen 2018, in order to arrive at the claimed invention. One of ordinary skill in the art would have been motivated with to do so because it was known that glucose glycation of α-Lactalbumin and ß-Lactoglobulin in a glycerol-based liquid system incubated at 50 °C for 12, 24, 48, 72, and 96 h using a water bath, yields glycated α-lactalbumin with three to four glucose molecules attached thereto after heating for 18, 72 and 96 h; and in the case of the ß-lactoglobulin, 5-6 glucose molecules were added onto the protein after heating for 18, 48, and 72 h; and because glycation occurred in glycerol-based liquid system at 50°C for 12, 24, 48, 72, and 96 h using a water bath thereby resulting in α-lactalbumin having 3-4 glucose moieties and ß-lactoglobulin having 5-6 glucose moieties. One of ordinary skill in the art would have had a reasonable expectation of success given that Chen 2018 used a glycerol-matrix-based system and studied with respect to the reaction extent, the site specificity influenced by the water activity and solvent matrix; and given that Chen 2018 glycated α-lactalbumin and ß-lactoglobulin derived from whey. Therefore, substituting α-lactalbumin and ß-lactoglobulin in Juneau’s composition with glycated α-lactalbumin and glycated ß-lactoglobulin comprising on average 3 to 4 glucose moieties and 5-6 glucose moieties, respectively; would support the instantly claimed method wherein the glycated α-lactalbumin has 1 to 12 glucose moieties, and the glycated ß-lactoglobulin has 1-16 glucose moieties by constituting some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or the use of a known technique to improve similar devises (methods, or products)in the same way and/or the application of a known technique to a known device (method, or product) ready for improvement to yield predictable results pursuant to KSR.
Regarding claim 7, Chen 2018 teaches the glucose glycation of ß-lactoglobulin (see Chen 2018, pg. 10558, abstract). Chen 2018 also teaches that the ß-lactoglobulin was provided by Davisco (Davisco Foods International, Inc., MN, USA) (see Chen 2018, pg. 10559, left column, paragraph 4). Additionally, Chen 2018 teaches the glycation extent of ß-lactoglobulin as depicted in Figure 3, where variant A and variant B of ß-lactoglobulin are marked with A and B (see Chen 2018, pg. 10562, Figure 3). Therefore, the composition taught by Chen 2018 comprises glycated ß-lactoglobulin where the glycated ß-lactoglobulin comprises glycated ß-lactoglobulin A and glycated ß-lactoglobulin B.
Regarding claim 8, Chen 2018 teaches Figure 3, where glycation extent of α-lactalbumin (i.e., Fig. 3A) and ß-lactoglobulin (i.e., Fig. 3B) are depicted (see Chen 2018, pg. 10562, Figure 3). It is noted that both α-lactalbumin and ß-lactoglobulin are glycated, and the highest percent intensity observed for α-lactalbumin appears to be present between 14600 and 14800 mass (Da) where a peak reaching 100% corresponding to 3 glucose moieties attached to α-lactalbumin is observed (see Chen 2018, pg. 10562, Figure 3A). Similarly, the highest peak present at an intensity of 100% can be observed for ß-lactoglobulin at about 19200 Mass (Da), where 5 glucose moieties are attached to variant A (see Chen 2018, pg. 10562, Figure 3B). Figure 3A also depicts a small peak which appear to represent non-glycated α-lactalbumin (see Chen 2018, pg. 10562, Figures 3A and 3B). However, the peak is low but not clearly identified as less than 5%.
MPEP 2112-2112.02 states that when a reference discloses all the limitations of a claim except for a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). In the instant case, Chen 2018 discloses the glycation extent of α-lactalbumin (i.e., Fig. 3A) and ß-lactoglobulin (i.e., Fig. 3B), where the peaks represent the percent abundance of the glycated proteins such that there is one small peak of non-glycated α-lactalbumin that appears to be less than 5 wt% thereby correlating to a total glycated protein content of at least 95 wt%.
The Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not Applicants’ total glycated protein weight percentage of α-lactalbumin and ß-lactoglobulin in the composition differs, and if so to what extent, from the total glycated protein weight percentage of α-lactalbumin and ß-lactoglobulin in the composition disclosed in Chen 2018. The cited art taken as a whole demonstrates a reasonable probability that the total glycated protein weight percentage of α-lactalbumin and ß-lactoglobulin in the composition of Chen is either identical or sufficiently similar to the claimed composition and that whatever differences exist are not patentably significant. Therefore, with the showing of the reference, the burden of establishing novelty or non-obviousness by objective evidence is shifted to the Applicants.
Merely because a function of a composition comprising α-Lactalbumin and ß-lactoglobulin exhibiting a particular glycated weight percentage is not expressly disclosed in a reference does not make the known composition patentable. The new composition comprising glycated α-Lactalbumin and ß-lactoglobulin produced via a particular process possess inherent functions which might not be displayed in the tests used in Chen 2018. Accordingly, the disclosure of Chen is a sufficient basis that the composition comprises at least 95 wt% α-Lactalbumin and ß-lactoglobulin in light of Chen’s glycation method.
In the alternative, even if the claimed composition is not identical to the Chen 2018 composition with regard to some unidentified functions, the differences between that which is disclosed and that which is claimed are considered to be so slight that the Chen 2018 composition is likely to inherently possess the same functions of the claimed composition particularly in view of the similar characteristics which they have been shown to share (i.e., a very low amount that appears to be less than 5 wt% non-glycated α-La and no non-glycated ß-Lg). Thus, the claimed composition would have been obvious to those of ordinary skill in the art under the meaning of 35 U.S.C 103.
Regarding claim 9, Chen 2018 teaches a composition comprising glycated α-lactalbumin where on average, each α-lactalbumin molecule was attached by three to four glucose molecules (See Chen, pg. 10561, bottom right column). However, Chen 2018 does not teach wherein at least 74% of the α-lactalbumin has 6 glucose moieties as recited in instant claim 4.
Deng’s deconvoluted mass spectra of α-lactalbumin heated with glucose at 50°C with 65% relative humidity over 0-10 h, depicts a peak corresponding to 6 glucose units, which starts to appear after 2 hours of incubation time (i.e., AG2), the peak becomes more prominent (i.e., a relative abundance of approximately 50%) at 3 h of incubation time or AG3 and said peak reaches a relative abundance of 100% at 4 h of incubation time or AG4 (See Dang, pg. 214, Figure 3), thereby constituting where at least 74% of the α-lactalbumin has 6 glucose moieties as recited in instant claim 4. As such, the teachings of Chen 2018 when combined with the teachings of Deng suggest the claim limitations as recited in instant claim 9
Additionally, MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. Therefore, the claimed 74% of the α-lactalbumin having 6 glucose moieties would have been obvious to one of ordinary skill in the art since the prior art percentage of α-lactalbumin having 6 glucose moieties (i.e., 100%) overlaps the claimed α-lactalbumin percentage having 6 glucose moieties (i.e., at least 74%). With respect to the percent of glycation, it is noted that Deng teaches that the number of glucose moieties that attach to α-La depends on specific parameters such as incubation time. Therefore, the amount of glucose moieties that attach to an α-La protein is clearly a result-specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal incubation time needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to modify the time of incubation as taught by Deng in order to increase the amount of glucose moieties that attach to α-La, and because an ordinary skilled artisan would have been able to utilize the teachings Deng to obtain various glycation parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the incubation time of the composition would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, because the combined teachings of the prior art are fairly suggestive of the claimed invention. Therefore, the teachings of Chen 2018 when combined with the teachings of Deng are suggestive of the claim limitations as recited in instant claim 9.
Regarding claim 10, Chen 2018 teaches a composition comprising glycated ß-lactoglobulin, where on average, each ß-lactoglobulin has five to six glucose molecules attached. However, Chen 2018 does not teach wherein at least 54% if the ß-lactoglobulin has 10 glucose moieties as recited in instant claim 10.
Chen 2012 teaches Intermediate-Moisture Food (IMF) model systems with glucose and other sugars; where the browning assay was used to determine the progress of the Maillard reaction (see Chen 2012, pg. 10675, right column, paragraph 2), and was measured by absorbance at 420 nm (See Chen 2012, pg. 10675, right column, paragraph 2). The absorbance in the systems containing fructose and glucose increased during storage, revealing the progress of the Maillard reaction between the reducing sugars and ß-Lg (See Chen 2012, pg. 10675, left column, paragraph 4). The absorbance rose more rapidly for the systems containing glucose than for those containing fructose, reaching 0.102 and 0.026, respectively, after the storage of 49 days at 25 °C (See Chen 2012, pg. 10675, left column, paragraph 4). The results indicated that glucose had a higher reaction rate than fructose with β-Lg (See Chen 2012, pg. 10675, left column, paragraph 4). For the glucose systems stored at 25 °C for 21 days (See Chen 2012, Supporting Information, pg. 2, Figure 2E), the result of the glycation extent showed that the attachment number varied from 4 to 11 and the most abundant product was glycated β-Lg with 7 attachments for both variants A and B (See Chen 2012, pg. 10675, left column, paragraph 4). Additionally, the mass spectra model systems containing glucose stored at 35°C are also depicted in Figures 3A-3D (See Chen 2012, Supporting Information, pg. 3, Figure 3). It is noted that at 35°C, for the systems containing glucose, 2 peaks corresponding to variant A and variant B appear at 19900 (i.e., B+10) and 19986 (i.e., A+10) at day 3 (See Chen 2012, Supporting Information, pg. 3, Figure 3C), suggesting that after three days of storage glycated β-Lg with 10 glucose attachments start to emerge. The percentage of B+10 glycated β-Lg and A+10 glycated β-Lg increases from approximately 10-20% on day 3 up to approximately 50-60% on day 7 (See Chen 2012, Supporting Information, pg. 3, Figure 3D), thereby constituting wherein at least 54% of the β-lactoglobulin has 10 glucose moieties as recited in instant claim 10.
MPEP 2144.05(I) states that "[i]n the case where the claimed ranges "overlap or lie inside ranges discloses by the prior art" a prima facie case of obviousness exists. Therefore, the claimed 54% of the ß-lactoglobulin having 10 glucose moieties would have been obvious to one of ordinary skill in the art since the prior art percentage of ß-lactoglobulin having 10 glucose moieties (i.e., approximately 50-60%) overlaps the claimed ß-lactoglobulin percentage having 10 glucose moieties (i.e., at least 54%). With respect to the percent of glycation, it is noted that Chen 2012 teaches that the number of glucose moieties that attach to ß-Lg depends on specific parameters such as incubation time and temperature. Therefore, the amount of glucose moieties that attach to an ß-Lg protein is clearly a result-specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal incubation time and temperature needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to modify the temperature and time of incubation as taught by Chen 2012 in order to increase the amount of glucose moieties that attach to ß-Lg, and because an ordinary skilled artisan would have been able to utilize the teachings Chen 2012 to obtain various glycation parameters with a reasonable expectation of success. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of the incubation time of the composition would have been obvious at the time of applicant's invention. Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because the combined teachings of the prior art are fairly suggestive of the claimed invention. As such, the teachings of Chen 2018 when combined with the teachings of Chen 2012 are suggestive of the claim limitations as recited in instant claim 10.
Regarding claims 11 and 19, Chen 2018 teaches glucose glycation of α-lactalbumin and ß-lactoglobulin at 50°C in a glycerol-based liquid system (See Chen 2018, pg. 10558, abstract). Chen prepared the glycated proteins by suspending protein powder in 30-100% glycerol solutions with a concentration of α-lactalbumin and ß-lactoglobulin (see Chen 2018, pg. 10559, right column, paragraph 2). The protein-glycerol solutions were mixed and incubated at 50 °C for 12, 24, 48, 72, and 96 h using a water bath (see Chen 2018, pg. 10559, right column, paragraph 3). However, Chen 2018 does not teach freeze-drying the solution to produce a powder, and incubating the powder in heated dry air as recite in instant claim 11.
Deng teaches that glycation of α-LA was performed by separately dissolving 10 mg powder/mL of α-LA and 3.5 mg/mL of glucose in 10 mM sodium phosphate buffer pH 8.0 (See Deng, pg. 212, right column, paragraph 1). These two solutions were mixed to reach molar ratio of total free amino groups (12 lysines, 1 arginine and the N-terminal): sugar reducing ends of 1:2 and subsequently freeze dried (in 30 mL batches) (See Deng, pg. 212, right column, paragraph 1). The freeze dried powder was incubated in a humidity control chamber at 50 °C with 65% relative humidity for 0, 1,2, 3, 4, 6, 8 and 10 h (See Deng, pg. 212, right column, paragraph 1).
Although, Deng discloses a method for glycation of α-lactalbumin which comprises the steps of: separately dissolving 10 mg powder/mL of α-LA and 3.5 mg/mL of glucose in 10 mM sodium phosphate buffer pH 8.0 (See Deng, pg. 212, right column, paragraph 1); mixing the solutions and subsequently freeze-drying them in 30 mL batches (See Deng, pg. 212, right column, paragraph 1); and incubating the freeze dried powder in a humidity control chamber at 50 °C with 65% relative humidity for 0, 1,2, 3, 4, 6, 8 and 10 h (See Deng, pg. 212, right column, paragraph 1). The claim limitations recited in instant claims 11 and 19 are drawn to a powder composition made by a certain process thereby constituting a product-by-process. Regarding product-by-process claims, the Federal Circuit has found that "[e]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." See MPEP 2113 and In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Furthermore, the Federal Circuit found that “[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes.” See MPEP 2113 and Amgen, Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). Therefore, in the instant case, the process steps recited in claims 11 and 19 do not aid in the patentability of a powder composition derived from a particular process. All that a prior art reference needs to show is the product of the process, i.e., a powder composition in this case. Thus, it is not necessary for Deng to teach the process steps recited in instant claims 11 and 19. It is sufficient for Deng to teach that the composition is in the form of a powder consisting of the components recited in instant claims 11 and 19, which are met and are discussed above. Additionally, since the composition obtained by the method of Deng is in the form of a powder (i.e., powdered α-Lactalbumin), Deng’s powdered α-Lactalbumin can be utilized in the composition of Chen 2018, since Chen 2018 teaches dissolving α-lactalbumin in glycerol. Therefore, the specific steps for the composition to result in a powder form are not structurally limiting. As such, the teachings of Chen 2018 and Deng are suggestive of the claim limitations as recited in instant claims 11 and 19.
Regarding claims 12 and 20, Chen 2018 teaches the use of whey proteins including α-lactalbumin and ß-lactoglobulin (see Chen 2018, pg. 10559, left column, paragraph 3), but does not expressly teach that the whey proteins were derived from whey protein isolate.
As previously discussed, Chen 2017 teaches that well-controlled glycation (generally limited to the early stages) has been proposed as a strategy to improve the physiochemical properties of dietary proteins (see Chen 2017, pg. 1, abstract). Chen 2017 establishes two systems (glycine-glucose and whey protein isolate (WPI)-glucose) to generate glycation products (See Chen 2017, pg. 1, abstract). As evidenced by Toro-Sierra, the protein fractions α-lactalbumin (α-La) and β- lactoglobulin (β Lg) represent almost 70% of the protein concentration in whey and are present in a mixed form with a ratio of approximately 20:80 (See Toro-Sierra, pg. 1032, right column, paragraph 1). As such the system taught by Chen 2017 comprising WPI and glucose, constitutes a WPI comprising α-lactalbumin and β- lactoglobulin.
Regarding claim 13, Chen 2018 teaches the preparation of glycated proteins, where the protein powder was suspended in 90-100% glycerol solutions with a concentration of α-lactalbumin and ß-lactoglobulin at 0.77 and 0.63 mM, respectively (see Chen 2018, pg. 10559, left column, paragraph 2); and the protein-glycerol solutions and the glucose-glycerol solutions (i.e., control) were mixed at a mass ratio of 1:1, with the mole ratio of amino and carbonyl groups at 1:2 (see Chen 2018, pg. 10559, left column, paragraph 3), thereby constituting where the ratio of WPI to glucose is in a molar ratio of free amino groups and reducing ends at 1:2. As such the teachings of Chen 2018 read on the claim limitations as recited in instant claim 13.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/CLAUDIA ESPINOSA/Patent Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654