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
2. Claims 1 – 16 are pending in this application.
Priority
3. This application is a national stage application of PCT/US2021/045515, filed August 11, 2021, which claims benefit of domestic application 63/064,489, filed August 12, 2020.
Election/Restrictions
4. Applicant ‘s election with traverse of group I, claims 1 – 10, drawn to a compound comprising a protein moiety covalently linked to a polysaccharide moiety via a phosphate bridge, filed August 19, 2025, is acknowledged. The traversal is on the ground(s) that Kozlowski et al. does not describe, exemplify, or enable a conjugate comprising a protein moiety and a polysaccharide moiety linked via a phosphate bridge because Kozlowski et al. broadly teaches selective modification at the reducing terminus of carbohydrate polymer, which may be conjugated to a wide variety of molecules and the support in paragraph [0115] and [0173] are too general that is not directed to any specific example. The examiner agrees that Kozlowski et al. may not anticipate the claimed invention. However, it would have been prima facie obvious for a person of ordinary skill in the art to substitute the non-phosphate linkages, such as oxime bonds, with the phosphate bridge, such as phosphate ester bond, as taught by Kozlowski et al. because Kozlowski et al. suggests that phosphate ester linkage is also a “physiologically cleavable” or “hydrolysable” bond and it is a weak linkage. Such substitution will yield predictable results. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to substitute the non-phosphate linkages, such as oxime bonds, with the phosphate bridge, such as phosphate ester bond, as taught by Kozlowski et al. because Kozlowski et al. teach the conjugate and other possible weak linkages.
The restriction requirement is still deemed proper and is therefore made FINAL.
Claims 11 – 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on August 19, 2025.
Claims 1 – 10 are examined on the merits herein.
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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
Claims 1 – 5 and 7 – 10 are rejected under 35 U.S.C. 103 as being unpatentable over Kozlowski et al. (US2015/0051371A1) in view of Matheis (Food Chemistry, 1991, Vol. 39, Issue 1, page 13 – 26, Reference included with PTO-892) and Wang et al. (Carbohydrate Polymers, 2018, Vol. 181, page 19 – 26, Reference included with PTO-892).
a. Regarding claims 1 – 5 and 7 – 10, Kozlowski et al. disclose water-soluble carbohydrate polymers which are monoderivatized at their reducing terminus, such that the carbohydrate polymers can be selectively conjugated at a single location (Abstract). Kozlowski et al. further discloses the conjugates of dextran with protein through a covalent attachment of a desired agent to the carbohydrate polymer (para. [0167] and [0200]). The linkage between carbohydrate and protein may be a hydrolytically unstable bond, such as phosphate ester bond (para. [0115]).
However, Kozlowski et al. do not teach the location where the phosphate bridge is bound to on the protein moiety.
Matheis teaches phosphorylation of food proteins with phosphorus oxychloride (Title). Phosphorylation with POCl3 may be a promising tool for improving functional and nutritional properties of food proteins. The amount of phosphorus covalently bound to proteins can reach up to 3.9% and the disgestibility of food proteins phosphorylated with POCl3 is not adversely affected (Abstract). The modification may be a means of eliminating the undesirable toxic and/or antinutritional properties of some proteins or other constituents; increasing or decreasing the solubility of proteins; changing the functional properties of proteins; improving the nutritional properties by the covalent attachment of limiting amino acids; and protein the protein against process-induced modification, such as the Maillard reaction (page 14, para. 1). Matheis discloses that only POCl3 seems to prove an economical and practical reagent for large scale application to food proteins (page 14, para. 6; page 15, para. 1). Matheis also illustrates the reactions:
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wherein the POCl3 is reacted with the -OH or -NH2 to form a phosphate, which bound to an oxygen atom and nitrogen atom on the protein (page 16, Equation (4) and (5)).
Wang et al. teach that phosphorylation is a key route to achieve varieties of biological activities for polysaccharides (Abstract). POCl3, a kind of phosphoryl chloride with high reactivity, is reported as a promising phosphorylation reagent to synthesize phosphorylated polysaccharide with high DS (page 19, Right Col., para. 2). POCl3/pyridine technique is successfully applied in phosphorylation of polysaccharide. This method allows for rapid and highly efficient synthesize of phosphorylated ASP with DS around 0.5 under mild conditions (page 24, Right Col., para. 3).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to combine protein moiety and polysaccharide moiety via a hydrolysable unstable bond, such as phosphate ester bond, as taught by Kozlowski et al. in view of Matheis and Wang et al. because Matheis and Wang et al. both teach the benefits of phosphorylating protein and polysaccharide and the use of POCl3 for the phosphorylation. One would have been motivated to combine protein moiety and polysaccharide moiety via a hydrolysable unstable bond, such as phosphate ester bond, as taught by Kozlowski et al. in view of Matheis and Wang et al. because of the disclosed benefits and the predicted reaction routes using POCl3 for phosphorylation of protein and polysaccharide. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to combine protein moiety and polysaccharide moiety via a hydrolysable unstable bond, such as phosphate ester bond, as taught by Kozlowski et al. in view of Matheis and Wang et al. because Kozlowski et al. already demonstrate conjugation of carbohydrate polymers and proteins through covalent bonds including phosphate ester linkages, Matheis teaches that phosphorylation of proteins with POCl3 is a well-established and effective method that maintains protein functionality and Wang et al. confirm the applicability of POCl3 phosphorylation to polysaccharides under mild and efficient conditions.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Kozlowski et al. (US2015/0051371A1) in view of Matheis (Food Chemistry, 1991, Vol. 39, Issue 1, page 13 – 26, Reference included with PTO-892) and Wang et al. (Carbohydrate Polymers, 2018, Vol. 181, page 19 – 26, Reference included with PTO-892) as applied to claims 1, 3 – 4, and 8 – 9 above, and further in view of Zhu et al. (Journal of Agricultural and Food Chemistry, 2010, Vol. 58, Issue 5, page 2988 – 2994, Reference included with PTO-892).
b. Regarding claim 6, the references teach the limitation discussed above.
However, these references do not teach the protein moiety is a whey protein.
Zhu et al. teach a covalently linked conjugates of whey protein isolate (WPI) and dextran (Abstract). Whey proteins are widely used as ingredients due to their excellent emulsification properties. However, whey protein are prone to heat-induced denaturation. Therefore, any improvement in the physiochemical and emulsifying properties under the conditions of high salt concentration, high heat temperature, and acidic pH range is needed. Dextran is chosen because it is a neutral molecule, avoiding the complication resulting from the formation of electrostatic complexes, which often occurs in mixtures of proteins with anionic polysaccharides. Dextran also has high solubility and low solution viscosity (page 1988, Right Col., para. 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the protein moiety as taught by Kozlowski et al. with whey protein in view of Zhu et al. because Zhu et al. teach that whey protein has been widely used and WPI-dextran conjugate has been exemplified in the art. It would have been obvious for one of ordinary skill in the art to do this because it is known in the art that WPI and dextran can be combined for improved properties. One of ordinary skill in the art would have had a reasonable expectation of success to substitute the protein moiety as taught by Kozlowski et al. with whey protein in view of Zhu et al. because the teachings teach the combination of WPI and dextran.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693