DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/25/2025 has been entered.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosures of the prior-filed applications, Application No. PCT/US2019/066922 filed 12/17/2019, provisional application 62/780,853 filed 12/17/2018 and provisional application 62/780,862 filed 12/17/2018 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Recited applications do not provide support for composition of egg white protein powder including recited percentage of ovomucoid, lysozyme, ovotransferrin and ovalbumin as claimed in claim 1 and hence application does not get the priority date of 12/17/2018 or 12/17/2019. Therefore, the effective filing date is the filing date 06/15/2021.
Status of the Claims
Claims 1, 2, 4-8, 13-17, 21, 25, 47, 49, 58, 60-62, 64, 73, 74, 76, 83, 91 and 97 are pending. Claims 1 is amended. Claims 3, 9-12, 18-20, 22-24, 26-46, 48, 50-57, 59, 63, 65-72, 75, 77-82, 84-90, 92-96 and 98-150 are cancelled. Claims 17, 25, 47, 49, 91 and 97 were withdrawn.
Claims 1, 2, 4-8, 13-16, 21, 58, 60-62, 64, 73, 74, 76 and 83 (claim set filed 06/25/2025) and are examined on the merits herein.
Withdrawal of Rejections
The response and amendment filed on 06/25/2025 are acknowledged. All of the amendment and arguments have been thoroughly reviewed and considered.
For the purposes of clarity of the record, the reasons for the Examiner's withdrawal and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner's response to arguments section.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 4-8, 13-16, 21, 58, 60-62, 64, 73, 74, 76 and 83 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 was amended to recite limitation for a dried egg white protein powder to consist of 10-20% ovomucoid, 0.1-3% lysozyme, 1-5% ovotransferrin and 70-80% ovalbumin. The Specification describes the composition of egg white protein powder in Table 5 (p. 88) for LOT A and LOT B, containing 11-12% ovomucoid, 2% lysozyme, 7-8% ovotransferrin and 73% ovalbumin. The distinct amount values do not provide support for the entire range of amount for each egg white protein. Additionally, the amount for ovotransferrin is not in the claimed range. The Specification provides results of the stability study on the amount and potency of egg white proteins in Tables 18-21 (pp. 106, 107). The Tables show the initial levels of egg white proteins in formulation at the beginning of the study as: 13% ovomucoid, 0.5% lysozyme, 4% ovotransferrin and 78% ovalbumin. However, not only these values do not cover the entire range of the claimed values, these results are obtained for capsules containing egg white proteins prepared formulation and not for egg white protein powder used to prepare formulations. These values cannot support the claimed values because during preparation of formulation and capsulation the relative amount of egg white proteins can be changed. As can be seen from the Specification preparation of formulation and its capsulation significantly changes the relative amounts of egg white proteins (compare Tables 5 and 18). Thus, Specification does not provide written description for the claimed ranges for egg white proteins.
It is known to one of ordinary skill in the art that ovomucoid, lysozyme, ovotransferrin and ovomucoid are the major proteins of egg white and the major egg allergens as evidenced by Zhu (Zhu et al. Trends in Food Sci. & Technol., 2018, 188-196; Abstract). Zhu teaches the relative amounts of these proteins in natural egg white (Table 1) which differ from claimed amounts in at least for ovotransferrin and ovalbumin. The Specification indicates that dried egg white protein powder was obtained from commercial sources (paragraph 0395), however, does not describe neither the source, nor why the claimed relative amounts for egg white proteins differ from natural composition. Thus, the claimed ranges of dried egg white protein are not supported by prior art.
Additionally, the recitation of the dried egg white powder is presented as a closed group containing four proteins, i.e. ovomucoid, lysozyme, ovotransferrin and ovalbumin, due to transitional phrase “consisting of”. Fig. 6 presents the HPLC chromatogram of the dried egg white powder that shows not only identified peaks for ovomucoid, lysozyme, ovotransferrin and ovalbumin but also additional small unidentified peaks which can indicate additional components in the egg white powder. Zhu teaches additional proteins in egg white present at lower amounts (p. 189, Table 1). Thus, it cannot be excluded that the instant egg white powder contains more than 4 recited proteins.
Therefore, the amount of egg white proteins in dried egg white powder and the presence of only four recited proteins are not described in the Specification in such a way as to confirm to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the claimed invention.
Claims 2, 4-8, 13-16, 21, 58, 60-62, 64, 73, 74, 76 and 83 do not resolve the issue mentioned above and are rejected.
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 2 and 13 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 2 recites: “the egg white protein formulation has about 0.05 wt% to about 2.5 wt% of egg white protein, or … 0.1 wt% to about 0.7 wt% egg white protein”. It is not clear if the percentage relates to the total egg white protein or to an individual protein. The scope and boundaries of claim 2 are not certain making claim 2 indefinite.
Claim 13 recites: “wherein a third amount of the first diluent is mixed with the third mixture”. Since the third mixture is mixed at a higher shear force in step (e) in claim 1 and is mixed with the lubricant in step (f) of claim 1, it is not clear on what step a third amount of the first diluent is mixed with the third mixture. The scope and boundaries of claim 13 are not certain making claim 13 indefinite.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 2, 4-8, 13-16, 21, 58, 60-62, 64, 73, 74, 76 and 83 are rejected under 35 U.S.C. 103 as being unpatentable over Raff (US 20160051639 A1 on record in IDS) in view Zhu (Zhu et al. Trends in Food Sci. & Technol., 2018, 188-196), Visschers (EP 1627570 A1) and Fendt (WO 2014111837 A1 on record in IDS).
Raff teaches egg white protein formulations, methods of manufacturing egg protein formulations and uses for egg protein formulations. Raff discloses that the egg white protein formulation is used for immunotherapy for egg allergy (Abstract). The method of making egg protein formulation comprises mixing egg white protein powder with diluent in a first blend (that reads on instant step (a)), adding diluent to make a second blend (that reads on instant step (c)), adding one or more diluent, filing agent and lubricant in a final blend (that reads on instant steps (d) and (f)) (paragraph 0007). Raff teaches that the first blend can be passed through a mesh screen before making second blend (paragraph 0013) that reads on instant step (b). Raff describes different diluents, including pregelatinized starch and microcrystalline cellulose (paragraph 0010) and multiple lubricants, including magnesium stearate (paragraph 0012). Raff discloses that formulation can comprise egg white powder or, alternatively, one or more proteins from egg powder (paragraph 0093). Raff describes characterization of ovomucoid, ovalbumin and lysozyme in egg white powder (paragraph 0007).
Raff teaches quantification of three egg white proteins, i.e. ovomucoid, lysozyme and ovalbumin in egg white powder (paragraph 0173) and does not exclude presence of other egg white proteins (paragraph 0093), however, does not teach ovotransferrin in egg white powder and does not teach mixing the third mixture at a higher shear force (step (e)) than in step (c).
Zhu teaches that the major egg allergens abundant in egg white include ovalbumin, ovomucoid, ovotransferrin and lysozyme (Abstract). Zhu discloses that ovotransferrin is one of the most allergenic protein in egg (p. 189, right column, last paragraph). Thus, ovotransferrin is inherently present in egg white or, alternatively, it can be added to formulation composed of individual egg white proteins.
Visschers teaches egg protein compositions that can be used as a gelling agent and can be employed in foodstuffs, beverages, oral care products and pharmaceutics (Abstract). Visschers discloses that compositions contain less conalbumin (ovotransferrin) removed by applying various treatments (paragraph 0007). Visschers describes that unmodified hen’s egg white has weight ratio of ovalbumin to conalbumin of about 4:1 to 5:1 (paragraph 0012). The preferred ratio in Visschers teaching is 20:1 (paragraph 0010). Visschers discloses that the preferred composition is in the form of powder (paragraph 0015) obtained by drying (paragraph 0029). Visscher’s provides examples of the relative amount of four egg white proteins compositions obtained by heat treatment (paragraph 0027). The composition treated for 2 min at 60°C has the following content: 13% ovomucoid, 0.6% lysozyme, 3.6% conalbumin (ovotransferrin) and 74% ovalbumin that reads on claim 1 limitation.
Fendt teaches preparation of formulations of acetylcholine receptor agonists (Abstract). Fendt teaches mixing the active drug with diluents, such as microcrystalline cellulose, in a pharmaceutical composition in a high shear mixing bowl to form granules which are then blended with lubricant, such as magnesium stearate, to form capsules (p. 21, lines 14-16, 22-24).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add ovotransferrin in reduced amount in preparation of formulation composed of egg white proteins for treatment of allergy as described in Raff teaching. One would have been motivated to do that since Zhu teaches ovotransferrin to be one of four major egg allergens besides ovalbumin, ovomucoid and lysozyme present in egg white. One would be motivated to reduce a relative amount of ovotransferrin since Zhu teaches ovotransferrin to be the most allergenic protein in egg white and hence lowering its amount will prevent possible allergenic reaction. A skilled artisan would have reasonably expected success in this combination since Raff and Zhu teach egg white proteins, Zhu provides description of the major protein components of the egg white and their role in allergy and Raff describes method of preparation of egg white protein formulation for treatment of allergy.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use compositions of dried egg white protein powder taught by Visschers including ovotransferrin in reduced amount in preparation of formulation composed of egg white proteins for treatment of allergy based on Raff and Zhu teachings. One would have been motivated to do that since Visschers teaches compositions that can be used as pharmaceutics (Abstract) and provides methods to reduce the amount of ovotransferrin. A skilled artisan would have reasonably expected success in this combination since Raff, Zhu and Visschers teach egg white proteins, Zhu provides description of the major protein components of the egg white, Visschers teaches preparation of the dried composition of egg white proteins and Raff describes method of preparation of egg white protein formulation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add step of high shear mixing of formulation before addition of lubricant from Fendt teaching to method of preparing egg white protein formulation based on Raff, Zhu and Visschers teachings. One would have been motivated to make this combination to provide uniform granules for encapsulation of egg white protein formulation. A skilled artisan would have reasonably expected success in this combination since Raff and Fendt described preparation of pharmaceutical formulations comprising active component, diluents and lubricants and including similar method steps. Thus, Raff, Zhu, Visschers and Fendt teachings render claim 1 obvious.
Regarding claim 2, Raff teaches the concentration of the egg white protein in the formulation from about 0.05% to about 50% w/w (paragraph 0102). Thus, Raff, Zhu, Visschers and Fendt teachings render claim 2 obvious because the instantly claimed range lies inside the range taught by Raff.
Regarding claims 4-7, Raff teaches blending the egg white protein powder with the diluent, ProSolv SMCC50, and passing the mixture through a mesh screen (paragraph 0262). After that the screened material is returned to the blender and the bag is rinsed with the same diluent, that can be considered as the second amount or portion of the second amount of the first diluent. After that the material is passed through mesh screen and blended and then the procedure is repeated (paragraph 0262). Although Raff does not explicitly describe the same protocol with the claimed first diluent, pregelatinized starch, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the same protocol can be applied to the first diluent to achieve complete and uniform resuspension of egg white powder in the first diluent. Thus, Raff, Zhu, Visschers and Fendt teachings render claims 4-7 obvious.
Regarding claim 8, Raff teaches adding the second amount of the first diluent in a second blend (paragraph 0007) indicating continuous blending of the mixture. Thus, Raff, Zhu, Visschers and Fendt teachings render claim 8 obvious.
Regarding claims 13 and 14, Raff teaches adding one or more of diluent, filing agent and lubricant to a final blend (paragraph 0007) after first and second amount of the first diluent was blended. Thus, Raff’s method may include addition of the third amount of the first diluent with or without the lubricant to the third mixture containing the second diluent. Therefore, Raff, Zhu, Visschers and Fendt teachings render claims 13 and 14 obvious.
Regarding claim 15, Raff teaches selection of diluents, filing agents and lubricants in paragraphs 0010-0012. Some of the lubricants can be considered diluents and/or filing agents, e.g. starch, polyethylene glycol or sodium chloride. Raff teaches that formulation can comprise addition of one or more lubricants (paragraph 0095). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the addition of more than one lubricant can represent addition of lubricant with the first or second diluent to increase solubility of the formulation. Thus, Raff, Zhu, Visschers and Fendt teachings render claim 15 obvious.
Regarding claim 16, Raff teaches passing magnesium stearate, which is a lubricant, through a 40 mesh screen before addition to the blend mixture (paragraph 0263). Since Raff does not exclude addition of more than one lubricant and some lubricants can be considered to be diluents as described above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to pass the mixture of diluent/lubricant through a mesh screen to separate aggregated particles and increase efficiency of lubrication. Thus, Raff, Zhu, Visschers and Fendt teachings render claim 16 obvious.
Regarding claim 21, Raff teaches alternative additions of components to the final blend, including diluents, filing agent, lubricant or glidant (paragraph 0007) and hence indicates that presence of all these components is not necessary. Silicon dioxide is recited as glidant in Raff teaching (paragraph 0076) and hence formulation can be free of silicon dioxide. The example of formulation without silicon dioxide is presented in Example 5: “ ProSolv SMCC 50 and ProSolv HD90 were included as diluents, Mannitol was included as a filling agent, Magnesium Stearate was included as a lubricant.” (paragraph 0210). The colloidal silicon dioxide, which is a glidant, was not included in the formulations. ProSolv SMCC 50 and ProSolv HD90 are the microcrystalline cellulose products (paragraph 0072). Although Raff does not include starch as a diluent in this particular formulation, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the example demonstrates that the formulation can be prepared with diluents and lubricant and in the absence of silicon dioxide. Thus, Raff, Zhu, Visschers and Fendt teachings render claim 21 obvious.
Regarding claim 58, Raff teaches egg white protein formulation prepared in batches of 5 kg (paragraph 0255, Tables 57-60). Thus, Raff, Zhu, Visschers and Fendt teachings render claim 58 obvious.
Regarding claim 62, Raff teaches multiple solid dosage forms for egg white protein formulation such as a tablet, a pill and a capsule (paragraph 0117). Thus, Raff, Zhu, Visschers and Fendt teachings render claim 62 obvious.
Regarding claims 60-61 and 64, Raff teaches blend and content uniformity analyses (Example 7, paragraphs 0213-0249). The analyses were conducted using size exclusion chromatography (paragraph 0216) and equations described in paragraphs 0217-0232). The results of the blend uniformity analysis are presented in Tables 25-28, that reads on claim 60. For the blend uniformity the RSD were from 2.08% to 5.17% (Tables 25-28) that reads on claim 61 limitation. Raff describes content uniformity analysis for plurality of dosage containers: “Multiple capsules or tablets are selected at random and a suitable analytical method is applied to assay the individual content of the active ingredient in each capsule or tablet. … The results show that from a uniformity perspective, all of the Blends were acceptable with <~5% RSD.” (paragraph 0242). The results of the content uniformity analysis are presented in Tables 29-31. That covers claim 64 limitation. Thus, Raff, Zhu, Visschers and Fendt teachings render claims 60-61 and 64 obvious.
Regarding claims 74 and 76, Raff teaches the egg white protein to comprise lysozyme, ovomucoid and ovalbumin the concentrations of which are characterized by HPLC (paragraph 0014). That reads on claims 74 and 76. Thus, Raff, Zhu, Visschers and Fendt teachings render claims 74 and 76 obvious.
Regarding claim 83, Raff teaches testing the potency of ovomucoid over time by ELISA (paragraph 0257) and presents the results in Table 66. Thus, Raff, Zhu, Visschers and Fendt teachings render claim 83 obvious.
Regarding claim 73, Visschers teaches compositions of hen’s egg white (paragraph 0027).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that egg white protein formulation taught by Raff can be based on egg white proteins obtained from chicken egg as described by Visschers. One would have been motivated to assume so with the reasonable expectation of success because Visschers describes preparation of dried powder composition of four major egg white proteins, chicken egg is the available source of egg white and the common egg allergy is usually developed to chicken eggs.
Response to Arguments
Applicant's arguments filed 06/25/2025) have been fully considered but they are not persuasive.
In response to Applicant’s arguments (addressing p. 7-10 of the Remarks) that the prior art of Raff, Zhu and Fendt does not teach the claimed composition for the egg white powder, these arguments are not persuasive because current rejection is based on combination of prior art of Raff, Zhu, Visschers and Fendt in which Visschers teaches the dried egg white protein composition having the claimed relative amounts of four major egg white proteins (paragraph 0027) as described in the rejection above.
Applicant argues (addressing p. 10 of the Remarks) that formulations of the recited proteins exhibited superior properties compared to the cited references. Applicant further argues that: “The application at Example 7 and Tables 18-19 demonstrates that the formulations consisting of the four egg white proteins (ovomucoid, lysozyme, ovalbumin, and ovotransferrin) were stable for protein mass and potency for up to 12 months at 25°C/60% humidity, and stable for at least 6 months at 30°C/65% (Table 20). … By contrast, the formulations of Raff et al. exhibited variations in potency of 30%+ before reaching stressed conditions. …Thus, not only are the claimed egg white protein contents not taught or suggested by the combination of references, but also the amended claims recite egg white formulations that exhibited comparatively superior manufacturing properties, with little to no observed loss in potency of the allergenic proteins.”, these arguments are not persuasive because:
As described in the previous Office Action, the presented unexpected results are not commensurate in scope with the claimed invention. “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." (MPEP 716(d)). In instant case, claim 1 does not have a limitation for the loss in potency for the four allergenic proteins and testing manufacturing properties and hence these properties are not within the scope of claimed invention. Additionally, Raff prepared formulations are intended to be used for treatment of allergy and Raff describes necessary quality control procedures such as assays of proteins by ELISA and size exclusion chromatography and assessment of content uniformity (paragraphs 0173, 0213-0249) and potency. Raff evaluates the potency of ovomucoid in 6-month and 11-month stability studies and describes that the potency of ovomucoid measured by ELISA and presented in Table 66 showed some variation but no consistent loss for up to 6 months (paragraph 0257).
Additionally, the current rejection is based on combination of prior art in which Visschers teaches the claimed dried egg white proteins composition (paragraph 0027) and Raff and Fendt teach the claimed method of preparation of formulation as described in the rejection above and hence the formulation prepared based on combination of prior art will necessarily possess the same potency and manufacturing properties.
Applicant’s arguments (addressing p. 11-12 of the Remarks) regarding prior art of Anchel are moot since the new ground of rejection does not rely on prior art of Anchel.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIOUBOV G KOROTCHKINA whose telephone number is (571)270-0911. The examiner can normally be reached Monday-Friday: 8:00-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila G Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/L.G.K./Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653