DETAILED ACTION
Status of the Application
Claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment of claims 1, 6-9, 14, 16, 18, 21, 24, 26, 28-29, 36-38 as submitted in a communication filed on 2/2/2026 is acknowledged.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/3/2025 and 2/2/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 1 is objected to due to the recitation of “alkaline phosphatase having at least 90% sequence identity to SEQ ID NO: 1”. To enhance clarity and to be consistent with commonly used claim language, the term should be amended to recite “alkaline phosphatase having at least 90% sequence identity to the polypeptide of SEQ ID NO: 1”. Appropriate correction is required.
Claim 1 is objected to due to the recitation of “(I) (i) the aliquot…(ii) the aliquot….(iii) the aliquot….or (iv) the aliquot….or (II) (i) the aliquot comprises….(ii) the aliquot comprises…or (iii) the aliquot…or (III) (i) the aliquot comprises…, (ii) the aliquot comprises…or (iii) the aliquot comprises…”. Sections (I), (II) and (III) each provide several options in the alternative which are all limiting the TSAC concentration of the aliquot and the duration of the filtration step. Therefore, if the intended limitation is the presence of only one of the 10 options provided in sections (I), (II) and (III), to avoid confusion, all the options in (I), (II) and (III) could be combined in a list of 10 options (e.g., options (i)-(x)) instead of three lists (e.g., (I), (II) and (III)), each having alternatives. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
Claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 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 pre-AIA the applicant regards as the invention. New grounds of rejection are necessitated by amendment.
Claim 1 (2-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 dependent thereon) is indefinite in the recitation of “(iii) the aliquot comprises a TSAC concentration of 2.8 mol/mol to about 3.0 mol/mol….” for the following reasons. The term “about” encompasses a range which includes values which are higher and lower than the recited reference value (e.g., 3.0 mol/mol, etc.). The term “from X to Y”, implies a range where X and Y are the endpoints. Therefore, in the absence of a clear definition of what is encompassed by the term “about”, the term "from X to about Y" is unclear and confusing because Y is an endpoint which is an undefined range. Correction is required.
Claim 1 (2-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 dependent thereon) is indefinite in the recitation of “the filtration step is held for X to Y hours” or “the filtration step is held for less than X hours” for the following reasons. As written, it is unclear if the term “held” refers to a delay before the filtration step is carried out, or if the term “held” refers to the duration of the filtration step. For examination purposes, no patentable weight will be given to the terms “the filtration step is held for X to Y hours” and “the filtration step is held for less than X hours” in claim 1 and dependent claims 6-7. Correction is required.
Claims 8 and 9 are indefinite in the recitation of “wherein the alkaline phosphatase concentration during the filtration step is 1.8 to …; and/or the TSAC concentration of the BDS is…” for the following reasons. First, it is unclear as to whether the alkaline phosphatase concentration to be measured is that of the harvest medium before it is filtrated or the medium after the filtration step. Second, even if one assumes that the alkaline phosphatase concentration to be measured is that of the filtrated medium, it is noted that the filtration step is a dynamic step. Therefore, the alkaline phosphatase concentration in the filtrated medium will change during the filtration step. If the intended concentration is that after the filtration step is over, the claims should be amended accordingly. For examination purposes, no patentable weight will be given to the term “wherein the alkaline phosphatase concentration during the filtration step is 1.8 g/L to X g/L”. Correction is required.
Claim 28 is indefinite in the recitation of “wherein step (d) comprises performing acid hydrolysis to release the TSAC from the recombinant alkaline phosphatase purified from the supernatant of the aliquot” for the following reasons. There is no antecedent basis in claim 1 for the recombinant alkaline phosphatase purified from the supernatant of the aliquot. For examination purposes, claim 28 will be interpreted as a duplicate of claim 1. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
Claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-37 remain 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.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that claim 1 has been amended to recite that the recombinant alkaline phosphatase has at least 90% sequence identity to the polypeptide of SEQ ID NO: 1. Applicant states that asfotase alfa, which comprises SEQ ID NO: 1, is a well characterized polypeptide that includes a soluble portion, an Fc region and a polyepitope bone targeting moiety. Applicant states that variants of this polypeptide have been generated and characterized in great detail. Applicant points out that the application describes different variants of alkaline phosphatases, Fc regions and negatively charged bone targeting moieties. Applicant is of the opinion that one of skill in the art would have unambiguously conclude that the Applicant was in possession of the full scope of the genus of polypeptides recited.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to the claims as well as the disclosure of the polypeptide of SEQ ID NO: 1. The Examiner also acknowledges that the prior art discloses a few alkaline phosphatases. However, the Examiner disagrees with Applicant’s contention that the entire genus of recombinant alkaline phosphatases is adequately described.
The polypeptide of SEQ ID NO: 1 has 726 amino acids. A polypeptide having at least 90% sequence identity to the polypeptide of SEQ ID NO: allows for 73 amino acid modifications (73 = 0.1x726; SEQ ID NO: 1 has 726 amino acids). The portion of the protein of SEQ ID NO: 1 that corresponds to an alkaline phosphatase consists of amino acids 1-485 of SEQ ID NO: 1. See alignment below. Assuming that the variants recited are limited to variants of the alkaline phosphatase region of the polypeptide of SEQ ID NO: 1, the claims encompass variants having up to 73 modifications within amino acids 1-485 of the polypeptide of SEQ ID NO: 1. The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula N!x19A/(N-A)!/A!, where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. Thus, the total number of variants that result from amino acid substitutions within amino acids 1-485 of the polypeptide of SEQ ID NO: 1 is 485!x1973/(485-73)!/73! or 1.89x10181 variants. If the modifications are made anywhere within the polypeptide of SEQ ID NO: 1, the total number of variants that result from amino acid substitutions within the polypeptide of SEQ ID NO: 1 is 726!x1973/(726-73)!/73! or 8.31x10194 variants. Neither the specification nor the prior art provide those structural features required in variants having the recited % sequence identity such that the desired alkaline phosphatase activity is observed. No structure/function correlation has been provided that would allow one of skill in the art to determine a priori from an infinite number of structural variants of the polypeptide of SEQ ID NO: 1 having the recited % sequence identity those variants having alkaline phosphatase activity.
As previously indicated, a sufficient written description of a genus of polypeptides may be achieved by a recitation of a representative number of polypeptides defined by their amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, the recited structural feature, i.e., 90% sequence identity to SEQ ID NO: 1, is not representative of all the members of the genus of proteins recited since there is no information as to which are the structural elements within the polypeptide of SEQ ID NO: 1 that are essential for the recited activity, which are the remaining structural elements required in the recited polypeptides in addition to those recited in the claims such that the desired activity is displayed, or a correlation between structure and function which would provide those unknown structural features. As explained in the prior Office action, the art teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. See the teachings of Witkowski et al., Tang et al. and Seffernick et al. previously discussed. Since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the entire genus of proteins required by the claimed method are adequately described by the teachings of the specification and/or the prior art.
Query = SEQ ID NO:1
Sbjct = alkaline phosphatase, tissue-nonspecific isozyme isoform 1 preproprotein [Homo sapiens]
Score Expect Method Identities Positives Gaps
1016 bits(2627) 0.0 Compositional matrix adjust. 485/485(100%) 485/485(100%) 0/485(0%)
Query 1 LVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQL 60
LVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQL
Sbjct 18 LVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQL 77
Query 61 HHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERS 120
HHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERS
Sbjct 78 HHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERS 137
Query 121 RCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEAL 180
RCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEAL
Sbjct 138 RCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEAL 197
Query 181 SQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWK 240
SQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWK
Sbjct 198 SQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWK 257
Query 241 SFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAI 300
SFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAI
Sbjct 258 SFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAI 317
Query 301 QILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTA 360
QILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTA
Sbjct 318 QILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTA 377
Query 361 DHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYA 420
DHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYA
Sbjct 378 DHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYA 437
Query 421 HNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHC 480
HNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHC
Sbjct 438 HNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHC 497
Query 481 APASS 485
APASS
Sbjct 498 APASS 502
Claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-37 remain 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 a method for producing of the protein of SEQ ID NO: 1, does not reasonably provide enablement for a method for producing alkaline phosphatase which is a variant of the polypeptide of SEQ ID NO: 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that claim 1 has been amended to recite that the recombinant alkaline phosphatase has at least 90% sequence identity to the polypeptide of SEQ ID NO: 1. Applicant states that the specification provides sufficient guidance to produce alkaline phosphatase variants with the claimed sequence identity. Applicant states that this guidance could be applied to polypeptides within the scope of the present claims without undue experimentation.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. The Examiner acknowledges the amendments made to the claims as well as the teachings of the specification. However, the Examiner disagrees with Applicant’s contention that the full scope of the claims is enabled by the teachings of the specification. While it is agreed that the prior art discloses methods to make variants of a polypeptide, the issue in the instant case is whether one of skill in the art would have to go through the burden of undue experimentation to enable the entire scope of the claims. As explained above, the number of structural variants that meet the recited % sequence identity is essentially infinite. Neither the specification nor the prior art provide those structural features required in variants having the recited % sequence identity such that the desired alkaline phosphatase activity is observed. No structure/function correlation has been provided that would allow one of skill in the art to determine from an infinite number of structural variants of the polypeptide of SEQ ID NO: 1 having the recited % sequence identity those variants having alkaline phosphatase activity. It is reiterated herein that while methods of generating variants of a polypeptide and enzymatic assays were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of proteins to find a protein with alkaline phosphatase activity. In the absence of (i) a rational and predictable scheme for selecting those proteins most likely to have the desired functional features, and/or (ii) a correlation between structure and activity, one of skill in the art would have to test an essentially infinite number of proteins to determine which ones have the desired functional characteristics. Therefore, contrary to Applicant’s assertions, the claimed genus of variants is not fully enabled by the teachings of the specification and/or the prior art.
Claim Rejections - 35 USC § 102 (AIA )
Claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 remain rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Godawat et al. (WO 2019/190752 published 10/3/2019; cited in the IDS).
This rejection has been discussed at length in the prior Office action. It is maintained for the reasons of record and those set forth below.
Applicant argues that claim 1 has been amended and that the hold time parameter of the filtration step (f) is dependent on the quantification of the TSAC content quantified at step (d). Applicant states that this step is clearly distinct from the method steps disclosed by Godawat et al. Applicant states that the TSAC content in the HCCF is assessed after the alkaline phosphatase is obtained from the cells during the harvest step. Applicant states that the method of the claims require the TSAC value to be measured from the aliquot obtained during fermentation, which is then used as a guide for the hold time of the filtration step.
Applicant’s arguments have been fully considered but not deemed persuasive to withdraw the restriction requirement. The claims as interpreted require the aliquot to have a TSAC concentration that ranges from less than 2.5 mol/mol to greater than or equal to 3.2 mol/mol. For the reasons extensively discussed above, no patentable weight has been given to the term “and the filtration step is held for X hours to Y hours). See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
As previously indicated, Godawat et al. teach that prior studies suggested that delaying harvesting time was associated with viability and TSAC decline and that the alkaline phosphatase is harvested at different time points such as 200 hours (8 days) or 12 days (page 38, paragraph [0131]). Godawat et al. teach that during manufacturing, the TSAC content is an important value and is monitored closely and that identification and quantitation of sialic acid in asfotase alfa samples at various stages of manufacture was performed by HPAE-PAD (page 50, paragraph [00168]).
While Applicant argues that Godawat et al. do not teach measuring the TSAC content prior to harvest, it is noted that Godawat et al. specifically teach measuring TSAC before and after harvest (page 57, Example 4, TSAC Measurement Before and After Harvest). Godawat et al. teach that the cell culture fluid (CCF) samples (before harvest) were taken at the end of the production bioreactor run and that the TSAC values ranged from 1.9 to 2.9 mol/mol. Godawat et al. teach harvesting at 200-288 hours (page 38, Harvest) and maintaining a constant temperature for 200 hours after inoculation, which is the culturing time (page 31, Temperature). Therefore, Godawat et al. teach measuring TSAC in an aliquot at 8.3 days (200 hours; end of the production bioreactor run) after inoculation and harvesting after obtaining an aliquot form the aqueous culture medium within 6 to 10 days (8.3 days) after inoculation, and measuring TSAC in said aliquot. Therefore, contrary to Applicant’s assertions, Godawat et al. anticipates the instant claims as interpreted.
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.
Double Patenting
Claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over (a) claims 1-17, 21-22 of U.S. Patent No. 11, 913,039, and (b) claims 1-18 of U.S. Patent No. 11,352,612.
These rejections have been discussed at length in the prior Office action. They are maintained for the reasons of record and those set forth below.
Applicant argues that the claims of U.S. Patent No. 11, 913,039 do not teach or suggest filtration step (f) of the present claims. Applicant states that filtration step (f) may be varied as a function of TSAC content that is determined from an aliquot of the aqueous culture medium obtained during the fermentation step. Applicant states that the description of U.S. Patent No. 11, 913,039 does not teach or suggest filtration step (f) of the present claims, particularly because the claims of the U.S. Patent No. 11, 913,039 do not teach or suggest any hold time parameters that occur after the harvest step. With regard to U.S. Patent No. 11,352,612, Applicant argues that the methods disclosed in the claims are directed to parameters that control the fermentation phase before the alkaline phosphatase is harvested from the cell culture and that step (f) of the claims of the instant application is directed to a post-harvest filtration step that occurs after the fermentation and after the alkaline phosphatase is separated from the cells. Applicant states that the methods are directed to different phases of alkaline phosphatase production and include different method steps at those different phases.
Applicant’s arguments have been fully considered but not deemed persuasive to overcome the instant rejection. As explained above, no patentable weight has been given to the term “and the filtration step is held for X hours to Y hours). See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation. The claims as interpreted require the aliquot to have a TSAC concentration that ranges from less than 2.5 mol/mol to greater than or equal to 3.2 mol/mol, harvesting the aqueous culture medium and filtration of the harvested aqueous culture medium to a filtration step.
Claims 1-17, 21-22 of U.S. Patent No. 11, 913,039 are directed in part to a method of producing recombinant alkaline phosphatase comprising (a) inoculating Chinese Hamster Ovary (CHO) cells expressing recombinant alkaline phosphatase; (b) culturing the CHO cells in culture medium; (c) isolating the recombinant alkaline phosphatase from the culture medium by at least one purification step to form harvest clarified culture fluid (HCCF) with a total sialic acid content (TSAC) of about 2.1 mol/mol to about 4.3 mol/mol; and (d) performing at least one additional protein purification step, wherein the culturing step is performed in a bioreactor having a volume of 0.25 L to 25000 L, and wherein the recombinant alkaline phosphatase comprises SEQ ID NO: 1. SEQ ID NO: 1 of U.S. Patent No. 11, 913,039 is identical to SEQ ID NO: 1 of the instant application. The specification of U.S. Patent No. 11, 913,039 specifically discloses measuring TSAC before and after harvest (Example 4, TSAC Measurement Before and After Harvest) as a preferred embodiment of the claimed method. The specification of U.S. Patent No. 11, 913,039 discloses taking TSAC samples of the cell culture fluid (CCF) before harvest at the end of the production bioreactor run, wherein the TSAC values range from 1.9 to 2.9 mol/mol, wherein harvesting occur at 200-288 hours and the temperature is maintained constant for 200 hours after inoculation. Therefore, specification of U.S. Patent No. 11, 913,039 discloses measuring TSAC in an aliquot at 8.3 days (200 hours; end of the production bioreactor run) after inoculation and harvesting after obtaining an aliquot form the aqueous culture medium within 6 to 10 days (8.3 days) after inoculation, and measuring TSAC in said aliquot, as a preferred embodiment of the claimed method. The specification of U.S. Patent No. 11, 913,039 discloses purification of samples taken for TSAC determination with a protein A column and the use of acid hydrolysis for determination of TSAC as a preferred embodiment of the method by which TSAC is determined. The specification of U.S. Patent No. 11, 913,039 also discloses centrifugation as one of the preferred embodiments of the method by which the harvest clarified culture fluid is obtained. Therefore, the method of claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 of the instant application as interpreted is deemed an obvious variation of the method of claims 1-17, 21-22 of U.S. Patent No. 11, 913,039 in view of the preferred embodiments disclosed.
Claims 1-18 of U.S. Patent No. 11,352,612 are directed in part to a method for producing an asfotase alfa having the sequence of SEQ ID NO: 1, wherein said method comprises (i) providing a 100 L to 25,000 L fed-batch bioreactor comprising CHO cells capable of expressing the asfotase alfa having the sequence of SEQ ID NO: 1, and a culture medium suitable for conducting such expression, the culture medium comprising from about 25 μM to about 300 μM zinc; and (ii) culturing the cells under conditions suitable to express the recombinant polypeptides; wherein the pH of the culture medium is about 6.7 to about 7.1, wherein zinc is added into said culture medium such that the zinc concentration in the culture medium is maintained at a concentration of about 25 μM to about 300 μM of zinc, wherein the zinc is added into said culture medium in at least one bolus, continuously, or semi-continuously; wherein the asfotase alfa having the sequence of SEQ ID NO: 1 comprises a total sialic acid content (TSAC) between 0.9 to 3.5 mol sialic acid/mol protein monomer. SEQ ID NO: 1 of U.S. Patent No. 11,352,612 is identical to SEQ ID NO: 1 of the instant application. The specification of U.S. Patent No. 11,352,612 discloses a method as claimed wherein a sample is taken for TSAC determination at day 8, 9 and 10 of culturing (Figure 8) as a preferred embodiment of the method claimed. The specification of U.S. Patent No. 11,352,612 discloses a method as claimed wherein the medium comprising the polypeptide of SEQ ID NO: 1 is harvested, wherein cell debris is removed by centrifugation, the supernatant is recovered, and a sample of this supernatant is used for TSAC analysis. Moreover, the specification of U.S. Patent No. 11,352,612 specifically disclose harvest clarification to remove intact cells and cell debris by filtration and ultrafiltration to (post-harvest UF) to concentrate the alkaline phosphatase. As such, it is clear that a preferred embodiment of the claimed invention is the harvest of the culture medium, the separation of the cell debris from the supernatant that has the alkaline phosphatase and the recovery of the alkaline phosphatase by filtration. Therefore, the method of claims 1-3, 5-9, 14, 16, 18, 21, 24, 26, 28-29, 31, 36-38 of the instant application as interpreted is render obvious by the method of claims 1-18 of U.S. Patent No. 11,352,612 in view of the preferred embodiments disclosed.
Conclusion
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
May 20, 2026
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