DETAILED ACTION
Background
The amendment dated February 11, 2026 (amendment) amending claims 2, 5, 72 and 74 and adding new claims 76-79 has been entered. Claims 2, 5, 12, 16, 22, 24, 26-31 and 62-79 as filed with the amendment have been examined. Claims 1, 3-4, 6-11, 13-15, 17-21, 23, 25 and 32-61 have been canceled.
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 .
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 2, 5, 12, 16, 22, 24, 26-31, 62-73, 76-78 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 14, 16 and 21 of U.S. Patent No. 12,011,016 (reference patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the recited method of “treating an aqueous suspension of a plurality of cells with a base until the pH of the aqueous suspension is about 8.5 to about 12.0” in claims 2 and 72 includes the claimed method of “perforating cell walls of a plurality of cells … performed at a pH of between about 8.5 to about 12.0 inclusive” in claim 1, step a) of the reference patent because attaining the recited pH requires use of a base or treating with a base. Moreover, all of the remaining steps b), c) and d) in claims 2 and 72 are otherwise identical to claim 1 of the reference patent.
In addition, the recited method “consisting of” steps a), b), c), d) and, optionally e) in claim 72 includes only the steps a), b), c), d) of claim 1 in the reference patent wherein the recited “perforating the cell walls… at a pH of about 8.5 to about 12.0, inclusive” in step a) comprises treating with a reductant which is treating with a base as in claim 3 of the reference patent reciting cysteine, glutathione and bisulfite reductants.
Further, in claims 2, 5 and 72 the recited step “e) optionally pasteurizing the protein composition” is not required by claims 2, 5 and 72. However, claim 11 of the reference patent recites the method “further comprising pasteurizing the protein composition” as in claims 2, 5 and 72.
Still further, in claim 5 the claimed method of “a) heating the plurality of cells to a temperature of about 50 °C to about 85 °C” includes the recited “heating to at least 60 °C after perforating” at a pH of about 8.5 to about 12.0, inclusive in claim 21 of the reference patent. Moreover, all of the remaining steps b), c) and d) in claim 5 are otherwise identical to claim 1 of the reference patent.
Claims 12, 62 and 73 are identical on scope to claim 2 of the reference patent as “about 8.5 to about 12.0” is the same as “between about 8.5 and about 12.0, inclusive”.
Claims 22 and 63 are identical to claim 12 of the reference patent.
Claim 71 includes the liquid portion comprising at least 50 wt% of cytoplasmic proteins from the plurality of cells in claim 12 of the reference patent.
Claims 24 and 64 are identical to claim 4 of the reference patent.
Claims 26 and 65 are identical to claim 5 of the reference patent.
Claims 27 and 66 are identical to claim 6 of the reference patent.
Claims 28 and 67 are identical to claim 7 of the reference patent.
Claims 29 and 68 are identical to claim 8 of the reference patent.
Claims 30 and 69 are identical to claim 9 of the reference patent.
Claims 31 and 70 are identical to claim 10 of the reference patent.
In claims 76, 77 and 78, the plurality of cells comprising microbial cells in claim 14 of the reference patent and the plurality of cells comprising fungal cells include the recited yeast cells as claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or 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.
Claims 2, 22, 26-31, 71-72, 76 and 78 are rejected under 35 U.S.C. 103 as unpatentable over EP 3670646 A1 to Ohly GmbH (Ohly GmbH), of record.
Regarding instant claims 2, 72, 76 and 78, Ohly GmbH at Abstract and [0008] discloses a method for preparing a yeast protein concentrate (claims 76 and 78) via pH adjustment to (at [0026]) a pH of 6.5 to 8.5, in a yeast cell suspension (“treating a plurality of cells with a base”),within which range the claimed treating with a base until the pH of the suspension is about 8.5 to about 12.0 lies, followed by lysing the plurality of cells. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", the Office considers that a prima facie case of obviousness exists. See MPEP 2144.05.I. The ordinary skilled artisan would have found it obvious in Ohly GmbH to treating its suspension of a plurality of cells with a base at the claimed pH because Ohly GmbH discloses that treating with a base at the claimed pH gives a desired protein solubilization.
Further, Ohly GmbH at [0027] discloses centrifuging the lysed cells to separate a soluble liquid portion of proteins from an insoluble solids fraction of cell components (“separating the aqueous suspension of the plurality of cells to form a solids portion and a liquid portion”). At [0028], Ohly GmbH discloses filtering wherein the liquid soluble fraction or liquid portion to allow all proteins below 300 kDa to pass and to remove non protein components, followed (at [0029]) by filtering to reduce the content of molecules smaller than 30 kDa (“filtering a liquid portion to form a filtrate and a retentate”). In addition, at [0030]-[0031] Ohly GmbH discloses methods that further comprise ultrafiltration or nanofiltration to remove molecules smaller than 30 kDa and as small as 5kDa (“concentrating the retentate to form a protein composition, thereby forming a protein composition from the plurality of cells”).
Ohly GmbH does not disclose e) pasteurizing a protein composition from its protein retentate; however, while the Office considers optional claim limitations, the claims do not require them.
The method disclosed in Ohly GmbH at [0008], [0026] and [0032] has the same or fewer steps as the method of claim 72. The Office considers the claimed method “consisting” of steps a), b), c) and d) to include the method disclosed in Ohly GmbH.
Regarding instant claims 22 and 71, the Ohly GmbH base adjustment, lysing and centrifuging is substantially identical to the protein purification claimed and disclosed and so appears to result in a protein composition that has at least 50% by weight of the cytoplasmic proteins of the plurality of cells as claimed. Absent a clear showing as to how the resulting amount of cytosolic proteins of the cells in Ohly GmbH differs from that of the protein composition as claimed, the Office considers the Ohly GmbH protein concentrate and its liquid portion as disclosed at [0008] and [0027-[0028] to have the claimed proportion of at least 50% by weight of cytoplasmic proteins of the extracted cells as in claim 22 and at least 10% by weight of the cytoplasmic proteins as in claim 71. See MPEP 2112.01.I.
Regarding instant claims 26-28, the protein liquid composition in Ohly GmbH appears to be made by substantially the same method of alkali extracting protein from a plurality of cells, followed by separating the liquids from solids and filtering the liquid as in the claimed method. Absent a clear showing as to how the amount of sodium hydroxide needed to raise the pH of a 2% w/v filtered suspension of a protein composition in Ohly GmbH from 3 to 9 differs from the amount of sodium hydroxide needed to raise the pH of the 2% w/v of the suspension of a protein composition from 3 to 9 as claimed, the Office considers the retentate of Ohly GmbH at [0008] and [0027-[0028] and [0030]-[0031] to have each of the claimed buffer capacity so that less than 3 mmol of sodium hydroxide will raise the pH of a 2% w/v suspension of the protein composition from 3 to 9 as in claim 26; further, considers the protein composition wherein H2S is detectable in an amount of less than about 0.1 ppm in a 45 mL headspace when L-cysteine is not added to 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 as in claim 27; and, considers the protein composition wherein H2S is detectable in an amount of at least about 0.2 ppm in a 45 mL headspace about 24 hours at 25 °C after 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 is brought to about 25 mM final concentration of L-cysteine as in claim 28. See MPEP 2112.01.I.
Regarding instant claim 29, the filtered liquid protein composition of Ohly GmbH by filtering the soluble fraction to reduce the content of molecules smaller than 30 kDa appears to be substantially the same protein composition as the claimed protein composition. Absent a clear showing as to how the content of protein compounds in the claimed protein composition differs from that of, the Office considers the ultrafiltered retentate of Ohly GmbH at [0008] and [0027-[0028] and [0030]-[0031] to comprise a protein composition comprises at least about 35%, on a dry weight basis, of compounds larger than 5 kDa. See MPEP 2112.01.I.
Regarding instant claims 30-31, Ohly GmbH at [0054] discloses a yeast protein concentrate (claim 30) and a protein rich food product containing it (a food as in claim 31).
Claims 2, 12, 22, 26-31 and 76 are rejected under 35 U.S.C. 103 as being unpatentable over CN 111172046 A to Gou et al. (Gou) in view of Degerli et al., "A novel concentration method for concentrating solutions of protein extracts based on dialysis techniques," Analytical Biochemistry, October 2001, 297(2):192-194 (Degerli), both of record.
All references to Gou refer to the Clarivate machine translation, a copy of which is provided with this Office action.
Gou at Abstract on page 2 discloses a method consisting of extracting protein from a microorganism (“plurality of cells”) comprising (1) preparing a chemical lysis solution of (at (1) on page 3) 1 to 20 wt% of sodium hydroxide and 0.5 to 10 wt% of sodium sulfite (“a) treating the aqueous suspension of the plurality of cells with a base until the pH of the aqueous suspension is about 8.5 to about 12.0”), ( 2) centrifugal separating plurality of cells (“b) separating an aqueous suspension of the plurality of cells to form a solids portion and a liquid portion”), and, after centrifuging sieving the protein liquid with a 400-mesh filter clothe to obtain the protein (“c) filtering the liquid portion to form a filtrate and a retentate”). In addition, at Example 2 on page 6 at (1) and (2), Gou discloses treating with a 1 wt% NaOH solution; and, on page 7, (9) and (10) Gou discloses additional centrifuging of a washed protein solution and then filtering at a pH of 10.0.
Further, and regarding instant claim 12 the Office considers the pH of a suspension comprising 1 to 20 wt% of sodium hydroxide and 0.5 to 10 wt% of sodium sulfite as in Gou and the pH of the claimed aqueous suspension to be substantially the same thing and considers the pH as remaining at the same level until it is actively changed. Accordingly, absent a clear showing as to how the pH of the aqueous suspension of the plurality of cells of protein compounds in the claimed protein composition differs from that of Gou, the Office considers the aqueous suspension and the separated liquid portion of Gou at Abstract and page 3 item (1) to be from about 8.5 to about 12.0 as in claim 2 and considers the Example 2 aqueous suspension and separated liquid portion in Guo to have a pH of about 9.0 to about 10.0 as in claim 12; further, the Office considers the pH of the basic aqueous medium comprising the plurality of cells to remain from about 8.5 to 12.0 during the b) separating to form a solids portion and considers a liquid portion as in claim 2, and for the same basic aqueous medium before and during the b) separating in Example 2 of Guo to remain from about 9.0 to about 10.0 as in claim 12; and, the Office considers the pH of the liquid portion of Guo at page 3, item (1) to be from about 8.5 to about 12.0 as in claim 2 and considers the Example 2 liquid portion of Guo to have a pH from about 9.0 to about 10.0 as in claim 12. See MPEP 2112.01.I.
Although Gou does not disclose the optional e) pasteurizing the protein composition; however, while the Office considers optional claim limitations, the claims do not require them.
Further, Guo does not disclose d) concentrating the retentate from the filtering to form a protein composition, thereby purifying the proteins from a plurality of cells; and, further does not disclose the concentrating at a pH of about 8.5 to about 12.
Degerli at page 192 discloses concentrating an aqueous protein solution by dialysis, thereby purifying the proteins in the solution while (at Table 1 on page 194) maintaining its pH. In the last paragraph on page 194, Degerli discloses methods useful for small and large scale operations.
Before the effective filing date of the present invention, the ordinary skilled artisan would have found it obvious in view of Degerli for Guo to further concentrate its protein after filtration by diafiltration as in Degerli. All references disclose methods of isolating aqueous proteins in basic solution. The ordinary skilled artisan in Guo would have desired to concentrate its product in the manner of Degerli to create a more stable product.
Regarding instant claims 22 and 71, the Guo base adjustment, lysing and centrifuging is substantially identical to the protein purification claimed and disclosed and so appears to result in a protein composition that has at least 50% by weight of the cytoplasmic proteins of the plurality of cells as claimed. Absent a clear showing as to how the resulting amount of cytosolic proteins of the cells in Example 2 of differs from that of the protein composition as claimed, the Office considers the Guo protein concentrate and its liquid portion as disclosed at the end of Example to have the claimed proportion of at least 50% by weight of cytoplasmic proteins of the extracted cells as in claim 22 and at least 10% by weight of the cytoplasmic proteins as in claim 71. See MPEP 2112.01.I.
Regarding instant claims 26-28, the protein liquid composition in Example 2 of Guo as modified by Degerli appears to be made by substantially the same method of alkali extracting protein from a plurality of cells, followed by separating the liquids from solids and filtering the liquid as in the claimed method. Absent a clear showing as to how the amount of sodium hydroxide needed to raise the pH of a 2% w/v filtered suspension of a protein composition in Guo from 3 to 9 differs from the amount of sodium hydroxide needed to raise the pH of the 2% w/v of the suspension of a protein composition from 3 to 9 as claimed, the Office considers the retentate of Guo at Example 2 as modified by Degerli to have each of the claimed buffer capacity so that less than 3 mmol of sodium hydroxide will raise the pH of a 2% w/v suspension of the protein composition from 3 to 9 as in claim 26; considers the protein composition wherein H2S is detectable in an amount of less than about 0.1 ppm in a 45 mL headspace when L-cysteine is not added to 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 as in claim 27; and, considers the protein composition wherein H2S is detectable in an amount of at least about 0.2 ppm in a 45 mL headspace about 24 hours at 25 °C after 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 is brought to about 25 mM final concentration of L-cysteine as in claim 28. See MPEP 2112.01.I.
Regarding instant claim 29, the filtered liquid protein composition of Example 2 of Guo appears to be substantially the same protein composition as the claimed protein composition. Absent a clear showing as to how the content of protein compounds in the claimed protein composition differs from that of, the Office considers the ultrafiltered retentate Example 2 of Guo as modified by Degerli to comprise a protein composition comprises at least about 35%, on a dry weight basis, of compounds larger than 5 kDa as in claim 29. See MPEP 2112.01.I.
Regarding instant claims 30-31 and 76, Guo at page 2, 2nd to last paragraph discloses a Pichia yeast protein concentrate (claims 30 and 76) and a food product containing it (a food as in claim 31).
Claims 5, 16, 62-63, 65-70 and 77 are rejected under 35 U.S.C. 103 as unpatentable over EP 3670646 A1 to Ohly GmbH (Ohly GmbH) in view of GB 1556297 to Pfizer (Pfizer), of record.
Regarding instant claims 5 and 77, Ohly GmbH at Abstract and [0008] discloses a method for preparing a yeast protein concentrate (claim 77) via pH adjustment to (at [0026]) a pH of 6.5 to 8.5, in a yeast cell suspension (“treating a plurality of cells with a base”),within which range the claimed treating with a base until the pH of the suspension is about 8.5 to about 12.0 lies, followed by lysing the plurality of cells. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", the Office considers that a prima facie case of obviousness exists. See MPEP 2144.05.I. The ordinary skilled artisan would have found it obvious in Ohly GmbH to treating its suspension of a plurality of cells with a base at the claimed pH because Ohly GmbH discloses that treating with a base at the claimed pH gives a desired protein solubilization.
Further, Ohly GmbH at [0027] discloses centrifuging the lysed cells to separate a soluble liquid portion of proteins from an insoluble solids fraction of cell components (“separating the aqueous suspension of the plurality of cells to form a solids portion and a liquid portion”). At [0028], Ohly GmbH discloses filtering wherein the liquid soluble fraction or liquid portion to allow all proteins below 300 kDa to pass to remove non protein components, followed (at [0029]) by filtering to reduce the content of molecules smaller than 30 kDa (“filtering a liquid portion to form a filtrate and a retentate”). In addition, at [0030]-[0031] Ohly GmbH discloses methods that further comprise ultrafiltration or nanofiltration to remove molecules smaller than 30 kDa and as small as 5kDa (“concentrating the retentate to form a protein composition, thereby forming a protein composition from the plurality of cells”).
Ohly GmbH does not disclose e) pasteurizing the protein composition from its protein retentate; however, while the Office considers optional claim limitations, the claims do not require them.
Ohly GmbH does not disclose a) heating the plurality of cells to a temperature of about 50 °C to about 85 °C in an aqueous suspension at a pH of from about 8.5 to about 12.0.
Pfizer at Preparation 3 on page 6 discloses a method of isolating protein from microbes including Saccharomyces cerevisiae at a pH of 11.5 while heating at 85 °C, followed by cooling the aqueous suspension to 25 °C and centrifuging, decanting the supernatant, and then repulping and centrifuging the residue (pellet) of the first centrifuging, followed by adding acid and recentrifuging at least twice, and then by freeze drying or concentrating the resulting liquid. The Office considers the Candida and Saccharomyces of Pfizer to be a plurality of cells and considers the centrifuging of Pfizer as separating the aqueous suspension of the plurality of cells to form a cell (solids) portion and a liquid portion protein containing the protein. Further, the Office considers freeze drying as concentrating a liquid protein composition.
Before the effective date of the present invention, the ordinary skilled artisan would have found it obvious in view of Pfizer for Ohly GmbH to heat its aqueous suspension of a plurality of cells to a temperature of about 50 °C to about 85 °C when treating the cells with a base. Both references disclose methods for isolating protein compositions from a plurality of yeast cells using a base, followed by cell disruption, separating non-proteins from liquid proteins and concentrating the liquid proteins. The ordinary skilled artisan in Ohly GmbH would have desired to use the heating as claimed and as in Pfizer to increase the solubility of its proteins in its aqueous suspension of a plurality of cells and to increase cell porosity and thereby increasing protein extraction yield.
Regarding instant claim 16, the Ohly GmbH as modified by Pfizer method as disclosed at [0008] of Ohly GmbH comprises base adjustment to a pH of about 8.5 and heating the plurality of cells to a temperature of about 50 °C to about 85 °C and (at [0019] of Ohly GmbH) maintains that pH during the separation of the aqueous suspension of the plurality of cells.
Regarding instant claim 63, the Ohly GmbH base adjustment, lysing and centrifuging is substantially identical to the protein purification claimed and disclosed and so appears to result in a protein composition that has at least 50% by weight of the cytoplasmic proteins of the plurality of cells as claimed. Absent a clear showing as to how the resulting amount of cytosolic proteins of the cells in Ohly GmbH differs from that of the protein composition as claimed, the Office considers the Ohly GmbH protein concentrate and its liquid portion as disclosed at [0008] and [0027-[0028] to have the claimed proportion of at least 50% by weight of cytoplasmic proteins of the extracted plurality of cells. See MPEP 2112.01.I.
Regarding instant claims 65-67, the protein liquid composition in Ohly GmbH appears to be made by substantially the same method of alkali extracting protein from a plurality of cells, followed by separating the liquids from solids and filtering the liquid as in the claimed method. Absent a clear showing as to how the amount of sodium hydroxide needed to raise the pH of a 2% w/v filtered suspension of a protein composition in Ohly GmbH from 3 to 9 differs from the amount of sodium hydroxide needed to raise the pH of the 2% w/v of the suspension of a protein composition from 3 to 9 as claimed, the Office considers the retentate of Ohly GmbH at [0008] and [0027-[0028] and [0030]-[0031] to have each of the claimed buffer capacity so that less than 3 mmol of sodium hydroxide will raise the pH of a 2% w/v suspension of the protein composition from 3 to 9 as in claim 65; considers the protein composition wherein H2S is detectable in an amount of less than about 0.1 ppm in a 45 mL headspace when L-cysteine is not added to 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 as in claim 66; and, considers the protein composition wherein H2S is detectable in an amount of at least about 0.2 ppm in a 45 mL headspace about 24 hours at 25 °C after 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 is brought to about 25 mM final concentration of L-cysteine as in claim 67. See MPEP 2112.01.I.
Regarding instant claim 68, the filtered liquid protein composition of Ohly GmbH by filtering the soluble fraction to reduce the content of molecules smaller than 30 kDa appears to be substantially the same protein composition as the claimed protein composition. Absent a clear showing as to how the content of protein compounds in the claimed protein composition differs from that of, the Office considers the ultrafiltered retentate of Ohly GmbH at [0008] and [0027-[0028] and [0030]-[0031] to comprise a protein composition comprises at least about 35%, on a dry weight basis, of compounds larger than 5 kDa. See MPEP 2112.01.I.
Regarding instant claims 69-70, Ohly GmbH at [0054] discloses a yeast protein concentrate (claim 69) and a protein rich food product containing it (a food as in claim 70).
Claims 5, 16, 62-70 and 77 are rejected under 35 U.S.C. 103 as being unpatentable over CN 111172046 A to Gou et al. (Gou) in view of GB 1556297 to Pfizer (Pfizer) and Degerli et al., "A novel concentration method for concentrating solutions of protein extracts based on dialysis techniques," Analytical Biochemistry, October 2001, 297(2):192-194 (Degerli).
All references to Gou refer to the Clarivate machine translation, a copy of which is provided with this Office action.
Gou at Abstract on page 2 discloses a method consisting of extracting protein from a microorganism (“plurality of cells”) comprising (1) preparing a chemical lysis solution of (at (1) on page 3) 1 to 20 wt% of sodium hydroxide and 0.5 to 10 wt% of sodium sulfite (“a) treating the aqueous suspension of the plurality of cells with a base until the pH of the aqueous suspension is about 8.5 to about 12.0”), ( 2) centrifugal separating plurality of cells (“b) separating an aqueous suspension of the plurality of cells to form a solids portion and a liquid portion”), and, after centrifuging sieving the protein liquid with a 400-mesh filter clothe to obtain the protein (“c) filtering the liquid portion to form a filtrate and a retentate”). In addition, at Example 2 on page 6 at (1) and (2), Gou discloses treating with a 1 wt% NaOH solution; and, on page 7, (9) and (10) Gou discloses additional centrifuging of a washed protein solution and then filtering at a pH of 10.0.
Further, and regarding instant claim 62, the Office considers the pH of a suspension comprising 1 to 20 wt% of sodium hydroxide and 0.5 to 10 wt% of sodium sulfite as in Gou and the pH of the claimed aqueous suspension to be substantially the same thing and considers the pH as remaining at the same level until it is actively changed. Accordingly, absent a clear showing as to how the pH of the aqueous suspension of the plurality of cells of protein compounds in the claimed protein composition differs from that of Gou, the Office considers the aqueous suspension and the separated liquid portion of Gou at Abstract and page 3 item (1) to be from about 8.5 to about 12.0 as in claim 5 and considers the Example 2 aqueous suspension and separated liquid portion in Guo to be about 9.0 to about 10.0 as in claim 62; further, the Office considers the pH of the basic aqueous medium comprising the plurality of cells to remain from about 8.5 to 12.0 during the b) separating to form a solids portion and a liquid portion as in claim 5 and considers the same basic aqueous medium before and during the b) separating in Example 2 of Guo to remain from about 9.0 to about 10.0 as in claim 62; and, the Office considers the pH of the liquid portion of Guo at page 3, item (1) to be from about 8.5 to about 12.0 as in claim 5 and the Example 2 liquid portion of Guo to have a pH from about 9.0 to about 10.0 as in claim 62. See MPEP 2112.01.I.
Although Gou does not disclose the optional e) pasteurizing the protein composition; however, while the Office considers optional claim limitations, the claims do not require them.
Further, Guo does not disclose d) concentrating the retentate from the filtering to form a protein composition, thereby purifying the proteins from a plurality of cells; and, further does not disclose concentrating the retentate at a pH of about 8.5 to about 12. And, Guo does not disclose a) heating the plurality of cells to a temperature of about 50 °C to about 85 °C in an aqueous suspension at a pH of from about 8.5 to about 12.0.
Pfizer at Preparation 3 and 4 on page 6 discloses a method of isolating protein from microbes including Saccharomyces cerevisiae at a pH of 11.5 while heating at 85 °C (Preparation 3) and 50°C (Preparation 4), followed by cooling the aqueous suspension to 25 °C and centrifuging, decanting the supernatant, and then repulping and centrifuging the residue (pellet) of the first centrifuging, followed by adding acid and recentrifuging at least twice, and then by freeze drying or concentrating the resulting liquid. The Office considers the Candida and Saccharomyces of Pfizer to be a plurality of cells and considers the centrifuging of Pfizer as separating the aqueous suspension of the plurality of cells to form a cell (solids) portion and a liquid portion protein containing the protein. Further, the Office considers freeze drying as concentrating a liquid protein composition.
Degerli at page 192 discloses concentrating an aqueous protein solution by dialysis, thereby purifying the proteins in the solution while (at Table 1 on page 194) maintaining its pH. In the last paragraph on page 194, Degerli discloses methods useful for small and large scale operations.
Before the effective date of the present invention, the ordinary skilled artisan would have found it obvious in view of Pfizer for Guo to heat its aqueous suspension of a plurality of cells to a temperature of about 50 °C to about 85 °C when treating the cells with a base. Both references disclose methods for isolating protein compositions from a plurality of yeast cells using a base, followed by cell disruption, separating non-proteins from liquid proteins and concentrating the liquid proteins. The ordinary skilled artisan in Guo would have desired to use the heating as claimed and as in Pfizer to increase the solubility of its proteins in its aqueous suspension of a plurality of cells and to increase cell porosity and thereby increasing protein extraction yield.
Before the effective filing date of the present invention, the ordinary skilled artisan would have found it obvious in view of Degerli for Guo to further concentrate its protein after filtration by diafiltration as in Degerli. All references disclose methods of isolating aqueous proteins in basic solution. The ordinary skilled artisan in Guo would have desired to concentrate its product in the manner of Degerli to create a more stable product.
Regarding instant claim 16, the Guo as modified by Pfizer method as disclosed at Example 2 on page 6 at (1) and (2) and, on page 7, (9) and (10) of Guo and Pfizer at Preparation 3 and 4 comprises base adjustment to a pH of about 8.5 and heating the plurality of cells to a temperature of about 50 °C to about 85 °C and maintains that pH during the separation of the aqueous suspension of the plurality of cells.
Regarding instant claim 63, the Guo base adjustment, lysing and centrifuging is substantially identical to the protein purification claimed and disclosed and so appears to result in a protein composition that has at least 50% by weight of the cytoplasmic proteins of the plurality of cells as claimed. Absent a clear showing as to how the resulting amount of cytosolic proteins of the cells in Example 2 of differs from that of the protein composition as claimed, the Office considers the Guo protein concentrate and its liquid portion as disclosed at the end of Example 2 to have the claimed proportion of at least 50% by weight of cytoplasmic proteins of the extracted cells. See MPEP 2112.01.I.
Regarding instant claim 64, Guo as modified by Pfizer method as disclosed at Example 2 on page 6 at (1) and (2) and, on page 7, (9) and (10) of Guo and Pfizer at Preparation 4 discloses isolation of protein by autolysis. The Office considers the claimed method that does not comprise the mechanical lysis of the plurality of cells to include the method disclosed in Guo as modified by Pfizer method as disclosed at Example 2 on page 6 at (1) and (2) and, on page 7, (9) and (10) of Guo and Pfizer at Preparation 4.
Regarding instant claims 65-67, the protein liquid composition in Example 2 of Guo as modified by Pfizer and Degerli appears to be made by substantially the same method of alkali extracting protein from a plurality of cells, followed by separating the liquids from solids and filtering the liquid as in the claimed method. Absent a clear showing as to how the amount of sodium hydroxide needed to raise the pH of a 2% w/v filtered suspension of a protein composition in Guo from 3 to 9 differs from the amount of sodium hydroxide needed to raise the pH of the 2% w/v of the suspension of a protein composition from 3 to 9 as claimed, the Office considers the retentate of Guo at Example 2 as modified by Degerli to have each of the claimed buffer capacity so that less than 3 mmol of sodium hydroxide will raise the pH of a 2% w/v suspension of the protein composition from 3 to 9 as in claim 65; considers the protein composition wherein H2S is detectable in an amount of less than about 0.1 ppm in a 45 mL headspace when L-cysteine is not added to 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 as in claim 66; and, considers the protein composition wherein H2S is detectable in an amount of at least about 0.2 ppm in a 45 mL headspace about 24 hours at 25 °C after 5 mL of a 2% (w/v) suspension of the protein composition at pH 7.0 is brought to about 25 mM final concentration of L-cysteine as in claim 67. See MPEP 2112.01.I.
Regarding instant claim 68, the filtered liquid protein composition of Example 2 of Guo appears to be substantially the same protein composition as the claimed protein composition. Absent a clear showing as to how the content of protein compounds in the claimed protein composition differs from that of, the Office considers the ultrafiltered retentate Example 2 of Guo as modified by Pfizer and Degerli to comprise a protein composition comprises at least about 35%, on a dry weight basis, of compounds larger than 5 kDa as in claim 29. See MPEP 2112.01.I.
Regarding instant claims 69-70 and 77, Guo at page 2, 2nd to last paragraph discloses a Pichia yeast protein concentrate (claims 69 and 77) and a food product containing it (a food as in claim 70).
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over CN 111172046 A to Gou et al. (Gou) in view of Degerli et al., "A novel concentration method for concentrating solutions of protein extracts based on dialysis techniques," Analytical Biochemistry, October 2001, 297(2):192-194 (Degerli) as applied to claim 2 above, and further in view of GB 1556297 to Pfizer (Pfizer).
As applied to claim 2, Guo at Example 2 on page 6 at (1) and (2) and, on page 7, (9) and (10) as modified by Degerli at page 192 discloses a method consisting of a) treating the aqueous suspension of the plurality of cells with a base until the pH of the aqueous suspension is about 8.5 to about 12.0; b) separating an aqueous suspension of the plurality of cells to form a solids portion and a liquid portion; c) filtering the liquid portion to form a filtrate and a retentate; and d) concentrating the retentate from the filtering to form a protein composition, thereby purifying the proteins from a plurality of cells, wherein the method is performed at a pH of about 8.5 to about 12.
Guo as modified by Degerli does not disclose a method that does not comprise mechanical lysis of the plurality of cells.
Pfizer at Preparation 3 and 4 on page 6 discloses a method of isolating protein from microbes including Saccharomyces cerevisiae at a pH of 11.5 while heating at 85 °C (Preparation 3) and 50°C (Preparation 4), followed by cooling the aqueous suspension to 25 °C and centrifuging and isolating the protein by autolysis, decanting the supernatant, and then repulping and centrifuging the residue (pellet) of the first centrifuging, followed by adding acid and recentrifuging at least twice, and then by freeze drying or concentrating the resulting liquid. The Office considers Preparation 3 and 4 of Pfizer to comprise the claimed lysis of the plurality of cells without mechanical lysis.
Before the effective date of the present invention, the ordinary skilled artisan would have found it obvious in view of Pfizer for Guo to heat to lyse its cells by treatment with a base. Both references disclose methods for isolating protein compositions from a plurality of yeast cells using a base, followed by cell disruption, separating non-proteins from liquid proteins and concentrating the liquid proteins. The ordinary skilled artisan in Guo would have desired to use the autolysis methods of Pfizer to facilitate extraction of protein from the plurality of cells in a pure form.
Allowable Subject Matter
Claim 73 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 74, 75 and 79 are allowable over the art.
The following is a statement of reasons for the indication of allowable subject matter:
The closest art of Ohly GmbH, Guo, Pfizer, and Vicik all fail to disclose or render obvious a method consisting of a) treating the aqueous suspension of the plurality of cells with a base until the pH of the aqueous suspension is about 9.0 to about 10.0; b) separating an aqueous suspension of the plurality of cells to form a solids portion and a liquid portion; c) filtering the liquid portion to form a filtrate and a retentate; and d) concentrating the retentate from the filtering to form a protein composition, thereby purifying the proteins from a plurality of cells, wherein the method is performed at a pH of about 9.0 to about 10.0 as in claim 73.
The closest art of Ohly GmbH, Guo, Pfizer, and Vicik all fail to disclose or render obvious a method consisting of a) heating a plurality of cells at a temperature of about 50 to about 85 °C; b) separating an aqueous suspension of the plurality of cells to form a solids portion and a liquid portion; c) filtering the liquid portion to form a filtrate and a retentate; and d) concentrating the retentate from the filtering to form a protein composition, thereby purifying the proteins from a plurality of cells, wherein the method is performed at a pH of about 8.5 to about 12.0 as in claims 74-75 and 79.
Response to Arguments
In view of the amendment dated February 11, 2026, the following rejections are withdrawn as moot:
The rejections of claims 2, 5, 16, 22, 24, 26-31 and 63-71 under 35 U.S.C. 103 as unpatentable over GB 1556297 to Pfizer in view of EP 3670646 A1 to Ohly GmbH;
The rejections of claims 2, 12, 22, 24, 26-30 and 71 under 35 U.S.C. 103 as being unpatentable over US 5,760,189 to Vicik et al., in view of EP 3670646 A1 to Ohly GmbH;
The rejections of claims 12 and 62 under 35 U.S.C. 103 as unpatentable over GB 1556297 to Pfizer in view of EP 3670646 A1 to Ohly GmbH and US 5,760,189 to Vicik et al.;
The rejection of claim 72 under 35 U.S.C. 103 as being unpatentable over CN 111172046 A to Gou et al. in view of EP 3670646 A1 to Ohly GmbH and Degerli et al., "A novel concentration method for concentrating solutions of protein extracts based on dialysis techniques," Analytical Biochemistry, October 2001, 297(2):192-194;
The rejection of claim 73 under 35 U.S.C. 103 as being unpatentable over CN 111172046 A to Gou et al. in view of EP 3670646 A1 to Ohly GmbH, Degerli et al., "A novel concentration method for concentrating solutions of protein extracts based on dialysis techniques," Analytical Biochemistry, October 2001, 297(2):192-194 and US 5,760,189 to Vicik et al.;
The rejection of claim 74 under 35 U.S.C. 103 as being unpatentable over CN 111172046 A to Gou et al. in view of GB 1556297 to Pfizer, EP 3670646 A1 to Ohly GmbH, and Degerli et al., "A novel concentration method for concentrating solutions of protein extracts based on dialysis techniques," Analytical Biochemistry, October 2001, 297(2):192-194;
and,
The rejection of claim 75 under 35 U.S.C. 103 as being unpatentable over CN 111172046 A to Gou et al. in view of GB 1556297 to Pfizer, EP 3670646 A1 to Ohly GmbH, and Degerli et al., "A novel concentration method for concentrating solutions of protein extracts based on dialysis techniques," Analytical Biochemistry, October 2001, 297(2):192-194 and US 5,760,189 to Vicik et al.
Applicant’s arguments with respect to 2, 5, 12,16, 22, 24, 26-31, 62-72 and 76-78 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Specifically, the current rejections do not rely on Pfizer for filtering or concentrating at a pH of about 8.5 to about 12.0, do not rely on Vicik at all, and do not rely on Guo with regard to claims 73-75.
Responsive to the positions taken in the remarks accompanying amendment dated February 11, 2026 (Reply), the positions have been fully considered but are not found persuasive for the following reasons:
Regarding the position taken in the Reply and unexpected results as shown in the instant specification at pages 206-209 and Examples 3 to 5, the alleged results are found persuasive with respect to the Pfizer reference.
Regarding the position taken in the Reply concerning Ohly GmbH, that reference does not depend on pH modification to render the rejected claims obvious.
Regarding the position taken in the Reply concerning Degerli, there is nothing in Degerli’s showing of a dialysis set up that suggests limiting the pH of the dialyzed protein. Rather, the ordinary skilled artisan would expect the dialysis in Degerli to function in any case where osmotic potential allows it to function; if, for example, one were to increase the pH in Degerli that would increase sodium or potassium concentration the ordinary skilled artisan would readily understand that osmotic balance would be maintained by increasing the cation concentration on the other side of the membrane. Moreover, where it is applied Ohly GmbH at [0027]-[0031] discloses sequential filtration steps that amount to concentration of a solution at the claimed pH.
The remaining positions taken are considered moot.
Conclusion
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/ANDREW E MERRIAM/Examiner, Art Unit 1791