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 Election/Restriction filed on September 15, 2025 is acknowledged. Claims 5-9, 13, 15, 27-45 were canceled and claim 46 was newly added. Claims 1-4, 10-12, 14, 16-26, 46 are pending in the instant application.
Election/Restrictions
Applicant elected without traverse Group I (claims 1-4, 10-12, 14 and 16-22) drawn to a method of formulating a product and without traverse SEQ ID NO:1 in the reply filed September 15, 2025. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP 818.03(a)).
The restriction is deemed proper and is made FINAL in this office action. Claims 23-26, 46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 23-26, 46 are withdrawn from consideration as being drawn to a non-elected invention.
Claims 1-4, 10-12, 14, 16-22 are examined on the merits of this office action.
Information Disclosure Statement
It is noted that Applicants have not filed an information disclosure statement under § 1.97(c). Applicant is reminded of 37 CFR § 1.56, which details Applicants duty to disclose all information known to be material to patentability.
Claim Objections
Claims 2-4, 10-12, 14, 16-22 are objected to for the following informality: the limitation of “A method according..” should be replaced with -The method according…
Claims 20-21 are objected to for the following informality: the limitation of “SEQ. ID NO:” should be replaced with -SEQ[[.]] ID NO:- in every instance found in the claim.
Claim 4 is objected to for the following informality: the limitation of “the mineral ions” should be replaced with -the bivalent mineral ions- given it is clear that Applicants are referring to bivalent given the markush group is bivalent mineral ions and bivalent mineral ions are recited earlier in the claim.
Claim Rejections - 35 USC § 112, First Paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 10-12, 14, 16-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), 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 applicant was in possession of the claimed genus.
Scope of the claims
The claims encompass broad methods of formulating a product (including food, personal care, or pharmaceutical products) comprising phosvitin or peptide fragments thereof that are substantially free of chelated mineral ions, formulated “in an effective preservative amount” with “additional ingredients suitable for formulating the product” Dependent claims further expand the scope by reciting peptide fragments with greater than 80% identity to SEQ ID Nos:1-14 (claims 20-21); specifying specific functional characteristics such as antimicrobial and antioxidant properties (see claims 18-19); inclusion of carriers, diluents or auxiliary agents (claim 14) and permitting a broad range of end-use products (i.e food, personal care, pharmaceutical, claim2) and of course being a preservative. Applicants define phosvitin as follows “The term “phosvitin”, as used herein, refers to the so named polypeptide occurring in the yolk of poultry eggs and having, in the case of chicken (Gallus gallus) phosvitin, an amino acid sequence as described by Byrne, M. et al., 1984, Biochemistry, 23, 4275-4279, and shown herein as SEQ.ID NO: 1, and further refers to any and all proteins comprising a sequence of amino acid residues which is (i) substantially identical to SEQ.ID NO: 1, or (ii) encoded by a nucleic acid sequence capable of hybridizing under at least moderately stringent conditions to any nucleic acid sequence encoding SEQ.ID NO: 1, but for the use of synonymous codons, including SEQ.ID NO: 2 set forth herein. Peptide fragments of phosvitin may be generated by chemical or proteolytic digestion, for example, digestion by trypsin. Phosvitin peptide fragments contain multiple serine residues and comprise generally at least 10, at least 25, at least 50, at least 75, at least 100, or at least 150 consecutive amino acid residues of SEQ.ID NO: 1, or of a sequence of amino acid residues that is (i) substantially identical to SEQ.ID NO: 1, or (ii) encoded by a nucleic acid sequence capable of hybridizing under at least moderately stringent conditions to any nucleic acid sequence encoding SEQ.ID NO: 1, but for the use of synonymous codons, including SEQ.ID NO: 2 set forth herein.
By the term “substantially identical” it is meant that two amino acid sequences preferably are at least 70% identical, and more preferably are at least 85% or 90% identical, and most preferably at least 95% identical, for example 96%, 97%, 98% or 99% identical” (See paragraphs 0052-0053). Thus, the term “phosvitin” encompasses variants of phosvitin as low as 70% sequence identity. Applicants also define fragments as “at least 10, at least 25, at least 50, at least 75, at least 100, or at least 150 consecutive amino acid residues of SEQ.ID NO: 1, or of a sequence of amino acid residues that is (i) substantially identical to SEQ.ID NO: 1”.
Thus, the claims cover a large genus of peptide compositions, structural variants (as low as 70% sequence identity for the full protein SEQ ID NO:1 and fragments thereof), and formulation types not limited to any particular sequence, fragment length or ingredient composition.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Actual Reduction to Practice
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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification provides only a single working example (Example 2) describing the preparation of mayonnaise containing 0.2% (W/W) phosvitin that was substantially free of mineral ions. This example demonstrates one embodiment of a food formulation (a mayonnaise emulsion) showing increased shelf-life stability when mineral free phosvitin was used. However, no examples or data are presented for any phosvitin peptide fragments, any formulation other than food emulsions (lotions, tablets, gels, beverages etc…), or any combinations demonstrating antimicrobial or antioxidant effects. Accordingly, the specification evidences actual reduction to practice only for one specific product (mayonnaise), not for the full scope of formulations or peptide variants encompassed by the claims.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
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 thereof.
Here, the specification fails to provide such characteristics to distinguish the claimed genus from the prior art and to demonstrate possession of representative species.
Physical/Chemical Properties
The specification provides only minimal characterization of the phosvitin material including mineral ion content is disclosed quantitively (e.g. 53 ppm Calcium, 2.56 ppm Fe3+ in EDTA treated preparations). There are no other physiochemical parameters described. The peptide fragments are not chemically characterized or purified to define distinct compositions of matter. Accordingly, the physical and chemical identity of the claimed compositions is insufficiently described to establish possession of the claimed genus or subgenera.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
While the specification asserts that the compositions may exhibit preservative, antimicrobial or antioxidant properties, these statements are speculative and unsupported by experimental data beyond the mayonnaise examples. The example demonstrates only emulsion stability, not microbial inhibition or antioxidant capacity. No data correlating structure (i.e. amino acid sequence (what amino acids are required), residue composition, or degree of mineral removal) with the biological or preservative function are discloses. The specification therefore fails to establish a correlation between the structural features of the phosvitin peptides and the claimed functional characteristics. The claimed functionality is not adequately supported between the structural features or the phosvitin peptides encompassed by the claims and the claimed function.
Method of Making
The specification does not describe any reproducible method of making the peptide fragments or formulating them into the broad classes of end use products claimed. The method for preparing the EDTA-treated phosvitin is briefly described but lacks specific purification parameters, buffer compositions, or yield data including for fragments and variants thereof. No guidance regarding enzymatic digestion, chemical synthesis, or fractionation of phosvitin into defined fragments. No guidance is given for preparing formulations outside the mayonnaise example-such as carriers, excipients, or stabilizers appropriate for cosmetic or pharmaceutical use.
Conclusion
In summary, while the specification demonstrates possession of a single mineral free phosvitin composition used in a mayonnaise formulation, it does not reasonably convey possession of the broader genus of phosvitin derived peptide fragments or greater than or equal to 70% identical variants claimed and the wide variety of “additional ingredients suitable for formulating the product” across food, cosmetic, and pharmaceutical applications. The disclosure therefore does not satisfy the written description requirement of 35 U.S.C. 112(a) because it fails to demonstrate that the inventors were in possession of the full scope of the invention as now claimed.
Claims 1-4, 10-12, 14, 16-22 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 method of formulating a product comprising full length phosvitin treated with EDTA and mayonnaise (oil in water emulsion) for effective preservation, does not reasonably provide enablement for use of any phosvitin fragments, any product type, any additional ingredients. 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.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of the claims
The claims encompass broad methods of formulating a product (including food, personal care, or pharmaceutical products) comprising phosvitin or peptide fragments thereof that are substantially free of chelated mineral ions, formulated “in an effective preservative amount” with “additional ingredients suitable for formulating the product” Dependent claims further expand the scope by reciting peptide fragments with greater than 80% identity to SEQ ID Nos:1-14 (claims 20-21); specifying specific functional characteristics such as antimicrobial and antioxidant properties (see claims 18-19); inclusion of carriers, diluents or auxiliary agents (claim 14) and permitting a broad range of end-use products (i.e food, personal care, pharmaceutical, claim2) and of course being a preservative. The claim encompasses any product (i.e. food, personal care product, pharmaceutical), any phosvitin fragment substantially free of mineral ions, any additional ingredient, any preservative effect, any product type. The claims are broad. The invention requires removal of mineral ions, achieving 95-99% purity and achieving antimicrobial and antioxidant properties. The nature of invention involves complex biochemical purification and diverse formulation science which increases the skill and experimentation required.
The State of the Prior Art
The art at the time of filing did not establish that any phosvitin or fragment thereof can be used as a preservative in combination with any product (including food, cosmetics) in any form. Samaraweera teaches phosvitin have a very strong affinity to bivalent metal ions calcium, magnesium and iron due to is phosphate molecules (see page R145, left column first paragraph). Samaraweera teaches that phosvitin is an antioxidant and is effective to in inhibit iron catalyzed hydroxyl radical formation (see page R145, right column, reduction of iron for the Fenton reaction, taught by Ishikawa, 2004). Phosvitin is known to have a strong metal binding affinity, antioxidant, emsulfication and antimicrobial properties (see Samaraweera, page R145). However, properties vary with metal content, ionic strength, pH and sequence and concentration (see R145 of Samaraweera, “metal chelating activity” and “Antioxidant activity”). Thus, predicting preservative effects across different product matrices, different fragment lengths, purity levels and ppm metal contents is not predictable.
The Predictability or Unpredictability of the Art/ The Relative Skill of Those in the Art
A person of ordinary skill in the art would have experience with protein purification and food formulation, but not necessarily specialized ability to remove metal ions less than 3 ppm simultaneously, determine effective preservative amounts across all product categories, maintain mineral free conditions. The level of skill is high and not supported by the specification.
As stated above, phosvitin is known to have a strong metal binding affinity, antioxidant, emsulfication and antimicrobial properties (see Samaraweera, page R145) that vary with metal content, ionic strength, pH and peptide sequence. Thus, predicting preservative effects across different product matrices, different fragment lengths, purity levels and ppm metal contents is not predictable. There is no guidance on how to extend the mayo example to other food, personal care, or pharmaceutical formulations.
Amount of Guidance/ The Presence or Absence of Working Examples
Applicants provide Table 1 (metal ppm before and after EDTA) and Example 2 (Two mayonnaise recipes). Applicants do not provide direction for generating any of the broad variety of claimed phosvitin fragments, determining the effective preservative amount in any matrix other than mayonnaise and with any additional ingredient, a method for selecting additional ingredients, any guidance for products other than a single mayo example. The disclosure lacks teaching commensurate with the breadth of the claims. Only one working example is provided (Example 2). This is insufficient to enable personal care products, beverages, dry formulations, pharmaceuticals and preservation effect across all compositions.
The Quantity of Experimentation Necessary
To practice the full scope, a person of ordinary skill in the art would need to engage in substantial protein purification optimization, determining preservative amounts for each possible formulation, testing activity across all product categories, generating or isolating phosvitin fragments that are effective preservatives in combination with any additional ingredients, identifying compatible formulations and ensuring the composition exhibits antioxidant and antimicrobial properties in each product type..
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 10-12, 14, 16-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 claims “(ii) formulating an effective preservative amount of the composition with additional ingredients suitable for formulating the product, to thereby form the product”. The wording is ambiguous and is reasonably susceptible to multiple different interpretations:
Formulating the composition itself to create a preservative effective formulation
Combining a preservative effective amount of the composition (phosvitin) of step (i) with additional ingredients to form the final product or
Formulating the preservative based on the ingredients added, i.e. additional ingredients create or define the “effective preservative amount”.
Because the claim does not make clear what is being formulated, what constitutes the preservative amount, or the role of the additional ingredients, one of ordinary skill cannot determine the metes and bounds of the claim with reasonable certainty.
In addition, Applicants define “effective preservative amount” as follows, the term “effective preservative amount”, as used herein, refers to an amount that is sufficient to effect a desired preservative effect. Such effect can include the prevention of spoilage of products, or the extension of the shelf life of a product, for example. The effective amount can vary depending on the product or the conditions to which the product is exposed. However, this definition does not resolve the ambiguity created by the grammatical structure of step (ii) and does not clarify whether the composition, the amount, or the final mixture is the subject of the “formulating” step.
Furthermore, the limitation of “additional ingredients suitable for formulating the product” is indefinite because the specification does not define which ingredients are considered “suitable” and provides only a single example (mayonnaise). It is therefore unclear what ingredients would fall within or outside the scope of the claim when applied to other food, personal care or pharmaceutical compositions.
Claims 2-4, 10-12, 14, 16-22 are also rejected due to their dependence on claim 1 and not further clarifying these points of confusion.
Claims 3 and 4 claim “A method according to claim 1, wherein the phosvitin or peptide fragments thereof are substantially free of bivalent mineral ions chelated thereto” and “A method according to claim 2, wherein the phosvitin or peptide fragments thereof are substantially free of bivalent mineral ions…” Claims 3 and 4 introduces “bivalent mineral ions” without prior antecedent basis. Claim 1 recites “mineral ions”, but does not define or limit to bivalent ions. Therefore, claims 3-4 fails to provide proper antecedent basis for “bivalent mineral ions”.
Claim 12 claims “A method according to any one of claims 2, wherein the phosvitin or peptide fragments thereof constitute at least about 95% (w/w), at least about 96% (w/w), at least about 97% (w/w), at least about 98% (w/w), or at least about 99% (w/w) of the composition.” However, it is unclear which “composition” is being reference for the calculation. Claim 1 introduces “(i) “a composition comprising phosvitin or peptide fragments thereof” and (ii) “an effective preservative amount of the composition with additional ingredients suitable for formulating the product”. It is ambiguous whether the percentages in claim 12 refer to the initial phosvitin containing composition (purity), the final formulated product of step (ii) which contains additional ingredients or some intermediate mixture or even the final product. Because the claim language permits more than on interpretation of what mixture the w/w percentage is calculated from, the metes and bounds of claim 12 are not reasonable clear. For examination purposes, the percent is the amount prior to including additional ingredients (basically the purity of the phosvitin).
Claim 14 claims “A method according to claim 2, wherein the composition further comprises at least one diluent, carrier, or auxiliary agent”. Similar to above, it is unclear which “composition” is being referenced. Claim 1 introduces “(i) “a composition comprising phosvitin or peptide fragments thereof” and (ii) “an effective preservative amount of the composition with additional ingredients suitable for formulating the product”. It is unclear whether claim 14 refers to the composition of step (i), or the final formulated composition of step ii), or some intermediate mixture or even the final product. Because the claim encompasses multiple reasonable interpretations, the metes and bounds are not clear. Claim 16 is dependent on claim 14 and is also rejected due not clarifying these points on confusion (also refers to “the composition”). It is possible Applicant is meaning to refer to the end product. If this is the case, a suggested amendment would be “wherein the product further comprises at least one….”
Claim 16 claims “the composition comprises…no more than about 148 ppm calcium ions and no more than about 3.2 ppm metallic mineral ions chelated thereto”. The phrase “chelated thereto” is ambiguous because, grammatically, it refers to the composition, whereas chelation is a property of the phosvitin or peptide fragments, not of the composition as a whole. Thus, there is two different possible interpretations. It is therefore unclear whether the ions are intended to be chelated to the phosvitin/peptide fragments or to the overall composition, and the claim is susceptible to more than on interpretation. Accordingly, the metes and bounds of the claim cannot be determined with reasonable certainty.
Claim 17 claims “A method according to claim 16, wherein in an aspect, the metallic ions are iron ions (Fe2+). Zinc…” The phrase “in an aspect” has no clear limiting effect in a claim and is reasonably interpreted either as a non-limiting example or as actual claim limitation. Because the claim language dos not make clear whether the metallic mineral ions are restricted to the recited ions or whether the clause is merely descriptive or optional, one of ordinary skill in the art would not be able to determine the metes and bounds of the claim with reasonable certainty.
Claims 18-19 are also rejected due to referring to “the composition”. However, it is unclear which “composition” is being referenced. Claim 1 introduces “(i) “a composition comprising phosvitin or peptide fragments thereof” and (ii) “an effective preservative amount of the composition with additional ingredients suitable for formulating the product”. It is unclear whether claims 18-19 refers to the composition of step (i), or the final formulated composition of step ii), or some intermediate mixture or even the final product. Because the claim encompasses multiple reasonable interpretations, the metes and bounds are not clear.
Claim 22 claims “wherein the phosvitin or peptide fragments thereof are substantially free from egg proteins naturally associated therewith”.
The term “substantially free of egg protein” in claim 22 is a term of degree for which the specification provides no definition, objective boundary or test method (unlike “substantially free of mineral ions” which is defined). The disclosure does not specify what concentration of residual egg protein is acceptable, how the level of such proteins are encompassed by the term. As a result, one of ordinary skill in the art cannot determine with reasonable certainty whether a given composition meets the limitation.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s)1-4, 10-12, 14, 16-19, 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US Patent NO. 9403870 B2) in view of Samaraweera, as evidenced by Ishikawa (Biosci, Biotechnol, Biochem, 68 (6), pages 1324-1331, 2004), Castellani (Journal of Chromatography B Volume 791, Issues 1–2, 5 July 2003, Pages 273-284) and Taborsky (Biochemistry, Vol. 2, No. 2, Mar.-Apr., 1963) as evidenced by Uptima (EDTA and EGTA chelating agents, FT-036291, accessed on 11/14/2025).
Claim interpretation of instant claim 1: for purposes of examination, claim 1 is being interpreted as reciting a method of formulating a product that includes two separate sequential steps. Under (i), the claims requires providing a composition comprising phosvitin or peptide fragments thereof that are substantially free of mineral ions. Under (ii) the claim is being interpreted as an amount of phosvitin or fragment thereof that has a preservative effect in the composition in combination with the additional ingredients. Regarding “substantially free of mineral ions”, Applicants define as mineral ions as less than 150ppm (see paragraph 0055).
Regarding claims 1-2, Wu discloses a method of extracting phosvitin and obtaining a purity of about 95% (see claim 20). Wu further teaches combining the phosvitin with foodstuff or a nutraceutical composition (claim 23). Wu specifically teaches “the invention may comprise a pharmaceutical or nutraceutical composition comprising a high-purity phosvitin, in combination with one or more pharmaceutically acceptable carriers, or a foodstuff comprising a high-purity phosvitin, or the above phosphopeptide” which would necessarily meet the limitations of formulating the phosvitin with an additional ingredient such as a food product.
Wu additionally teaches “a method of promoting health by administering to a subject the pharmaceutical or nutraceutical composition or a foodstuff described above, in an amount sufficient to effect a health benefit”.
Wu is silent to the limitation of combining substantially metal free phosvitin (Fe2+, Zn2+, Mn2+ and Ca2+) with the foodstuff of Wu with the residual amounts specified in the instant claims.
However, Samaraweera teaches phosvitin have a very strong affinity to bivalent metal ions calcium, magnesium and iron due to is phosphate molecules (see page R145, left column first paragraph). Samaraweera teaches interactions of phosvitin with Fe depend on Fe concentration and two phosphate molecules (of the protein) to complete the binding process. Additionally, EDTA was capable of releasing bound Fe from phosvitin (see page R145, left column). Samaraweera teaches that phosvitin is an antioxidant and is effective to in inhibit iron catalyzed hydroxyl radical formation (see page R145, right column, reduction of iron for the Fenton reaction, taught by Ishikawa, 2004). As evidenced by Ishikawa, the phosvitin used was apo-phosvitin, or metal free (see Ishikawa, page 1325, left column, last paragraph) and had less than 0.03 iron atoms per phosvitin molecule.
Castellani teaches extraction of highly purified (greater than 98%) and free of metal phosvitin (see abstract). Castellani teaches “Depending on the isolation method used, egg yolk phosvitin contains between three and six atoms of iron per molecule. The study of iron binding activity of purified phosvitin implies to obtain the protein metal free. This was usually achieved by the use of separation methods after isolation procedure” (see Introduction, second paragraph). Wu specifically teaches content of 0.03 and 0.16 atoms of Fe and Mg per molecule of protein (see page 282, left column) with purification. This roughly equates to 48 ppm Fe and 110 ppm Mg which falls within the definition of substantially free of mineral ions (Atomic weight of Fe-55.85 g/ml, protein MW=35000 gm/ml, ((.03*55.85/35000)x106 , equates to 45 ppm iron; Atomic weight for Mg 24.3g/mol, protein MW35000 g/mol, roughly 111 ppm Mg). Pvt was essentially free of divalent metal counter ions such as iron and magnesium, without need of further chromatography or time-consuming dialysis process (see section 4.3, second paragraph). We conclude that the purification process, using a rapid anionic-exchange chromatography at pH 5.0, allows us to obtain purified phosvitin with a relatively high yield (1.7% of egg yolk dried matter, that is to say 85% of total egg yolk phosvitin), using aqueous solvent solutions throughout the process. The obtained yield is comparable to those described by other authors who used organic solvents in their extraction procedures. Moreover, a high degree of purity (at less 98%) and a protein free of polyvalent metals were obtained”(see conclusion paragraph). This is ideal for the purpose of including in food (using only food grade solutions).
Taborksy teaches obtaining metal free phosvitin via use of EDTA and dialysis (which the instant application utilizes EDTA for removal of metal ions) (see abstract, page 267, “experimental”).
It would have been obvious before the effective filing date of the claimed invention to modify the phosvitin of Wu to employ a substantially metal-free phosvitin in formulating Wu’s food or nutraceutical compositions. One of ordinary skill the in the art would have been motivated to do so because metal free iron retains empty metal binding sites and would be therefore capable of binding iron present in the food composition and exert is antioxidative properties. Given Samaraweera’s explicit teaching that metal binding is concentration dependent and governed by the number of available phosphate groups, a person of ordinary skill would reasonably expect that removing the prebound iron would improve the protein’s ability to bind iron form the surrounding environment/formulation. There is a reasonable expectation of success because the references demonstrate that known extraction and EDTA methods (which are also utilized in the instant invention) reproducibly remove metal and produce predictable metal free phosvitin, with antioxidant properties, which has already been successfully used in food related/antioxidant contexts.
Regarding claims 3-4, the combination of Wu in view of Samaraweera, Castellani and Taborsky render obvious use of substantially free of bivalent mineral ions including Fe2.
Regarding claims 10-11, 16-17, Samaraweera, Ishikawa and Castellani teach substantially metal free phosvitin with residual metal levels well below the threshold. Ishikawa teaches apo-phosvitin containing less than 0.03 Fe atoms per molecule, Castellani teaches phosvitin with 0.03 Fe atoms and 0.16 mg atoms per molecule and states “substantially free of mineral ions”. Samaraweera and Taborsky both teach use of EDTA (which is what is used in the instant application) to produced metal free phosvitin. Even though the prior art doesn’t state that all of Ca2+, Fe2+, Zn2+ and Mn2+ are removed, as evidenced Uptima (see attached handout), EDTA chelates Ca2+, Fe2+, Zn2+ and Mn2+ and thus it would expected that by removing metals from phosvitin using EDTA that all of the bivalent mineral ions would inherently be removed with a very low residual level. Nevertheless, it would have been obvious to optimize the degree of metal removal because the prior art teaches that phosvitin’s functional behaviors is dictated by the amount of bound divalent metal and that EDTA chelates bivalent metals. Adjusting purification conditions in order to obtain lower residual metal content represents a routine optimization of a result effective variable and a person of ordinary skill would reasonably expect that increasing the extend of metal removal would predictably reduce the ppm values of the chelated ions and improving iron binding capacity of the phosvitin.
Regarding claim 14, Wu teaches including acceptable carriers or additional auxiliary agents (See Column 8, lines 1-12, column 7, last paragraph).
Regarding claims 18-19, Wu in view of Samaraweera, Castellani and Taborsky teach the same formulation of the instant claims (metal free Phosvitin) in combination with additional ingredients and thus, would inherently have the properties of being antimicrobial and antioxidant. In addition, these properties are well recognized properties of phosvitin in the prior art (see Samaraweera for example).
Regarding claim 21, Wu teaches wherein the phosvitin peptide fragment comprises instant SEQ ID NO:9 (see Table 4, first sequence).
Regarding claims 12, 16 and 22, Wu teaches a purity of 50-95% following extraction. In absence of any guidance with regards to “substantially free” from egg proteins naturally associated thereto”, this will be interpreted as 10%. Thus, a purity of 95% would fall within the claimed amount for instant claim 22 and also for instant claims 12 and 16. Nevertheless, phosvitin purity is a result effective variable and it would have been obvious to optimize to achieve optimal purity (less contamination) for therapeutic purposes and high therapeutic activity.
Claim(s)1-4, 10-12, 14, 16-22 are rejected under 35 U.S.C. 103 as being unpatentable over Wu (US Patent NO. 9403870 B2) in view of Samaraweera, as evidenced by Ishikawa (Biosci, Biotechnol, Biochem, 68 (6), pages 1324-1331, 2004), Castellani (Journal of Chromatography B Volume 791, Issues 1–2, 5 July 2003, Pages 273-284) and Taborsky as evidenced by Uptima (EDTA and EGTA chelating agents, FT-036291, accessed on 11/14/2025),as applied to Claim(s) 1-4, 10-12, 14, 16-19, 21-22 above, in further view of Byrne (Biochemistry, pages 4275-4279).
The combined references are silent to the sequence of SEQ ID NO:1 (full length phosvitin from chicken). Wu teaches extracting phosvitin and including in food (claim 1 and claim 23).
Samaraweera teaches of properties of full length phosvitin and references Byrne for the full sequence which is identical to instant SEQ ID NO:1 (See Figure 1, page R144)..
Byrne teaches that phosvitin comprises SEQ ID NO:1 (see page 4277).
It would have been obvious before the effective filing date of the claimed invention to use full-length phosvitin (as taught by Byrne and referenced in Samaraweera comprising instant SEQ ID NO:1) in the food products of Wu because each reference teaches phosvitin’s functional properties—emulsifying capacity, antioxidant activity, and metal-binding activity—in food systems, and substituting the known full-length protein for the phosvitin peptides of Wu represents the use of a known protein for its known purpose. Under KSR, when a technique has been used to improve one device, and a POSA would recognize that it would improve a similar device the same way, the combination is obvious. Here, substituting full-length phosvitin for known phosvitin fragments in food systems would have yielded predictable results (proteins that bind metal ions and have antioxidant properties), as the art teaches that full-length phosvitin inherently possesses the same food-functional properties.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/ Examiner, Art Unit 1654