DETAILED ACTION
Status of Claims:
Claims 1, 10-19 and 22-24 are pending.
Claim 1 is amended.
Claims 8, 9, 25, and 26 are 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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/19/2025 has been entered.
Response to Arguments
Applicant's arguments filed 9/19/2025 have been fully considered but they are not persuasive.
The applicant argues that Giese does not teach the steps in the claimed order. The applicant does not provide any support for the argument that Giese fails to provide a purification process in the order as claimed by the instant claims. It is acknowledged in the previous rejection that Giese does not explicitly teach the claimed buffer concentration and pH in an embodiment with viral inactivation and neutralization. However Giese teaches viral inactivation and neutralization of an eluted protein mixture (see Giese para. 0465). It would have been obvious to one skilled in the art to perform viral inactivation and neutralization of the protein mixture of Giese eluted with a elution buffer with a concentration of between 100 and 200 mM because it is the simple addition of a known treatment step to a known process, obviously resulting in the destruction of viruses, with an expectation of success. Further no unexpected or significant results are show as a result of the claimed order of steps.
The applicant argues that Table 4 (results shown in Table 5) show the significance between a pH of 3 and 3.5. This argument is not persuasive because the change in turbidity does not appear to be unexpected or significant between a pH of 3 and 3.5 as it is known in the prior art that pH effects the turbidity (low pH results in aggregation and precipitation and results in a turbid elution pool) see Luo pg. 52, 2nd paragraph left column). It is further noted that the claimed range of pH 3.3 to 3.5 is not disclosed in the specification as being significant.
The applicant argues that Luo “fails to solve the turbidity problem”, that Luo teaches that increasing the salt concentration increases turbidity and that Lue teaches that higher salt concentrations during elution are not ideal. Although Luo states that the turbidity problem is not solved it does not discount that Luo teaches the effect that concentration and pH have on turbidity. Further Luo teaches that higher concentrations would likely result in lower turbidity (see pg. 64, last paragraph left column). As Giese teaches concentrations within the claimed range (150mM) (see claim 30) and above the claimed range (244mM) (see Table 8) are effective for elution one skilled in the art would have found it obvious to use concentrations within the claimed rage within an expectation of success.
In view of the amendments Gillespie is no longer used in the current rejection.
The Double patenting rejections are maintained.
The previous 112 rejections are withdrawn in view of the amendments.
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 1, 10-19 and 22-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-26 of copending Application No. 17/922,742 in view of Blaisdell (WO 2009/058769).
The claims of the copending application disclose the all the limitations of the instant application except “wherein the neutralized protein mixture from step (e) is filtered using a 0.2 µm filter”. Blaisdell teaches filtering a neutralized protein mixture after viral inactivation using a 0.2µm filter (see para. 0113).
The copending application and Blaisdell are analogous inventions in the art of protein processing. It would have been obvious to one skilled in the art to aa the filtration step of Blaisdell after the neutralization because it is the simple addition o f a known treatment step to a known mixture, obviously resulting in filtration of the eluted mixture, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 10-19, and 22-24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-25 of copending Application No. 17/922,729 in view of Ramasubramanyan et al (US 2019/0062419) and Blaisdell (WO 2009/058769).
Regarding Claim 1:
The claims of the copending application disclose process of purifying a protein mixture comprising; a. Loading the protein mixture of antibody or fragment thereof and impurities onto Affinity column with a suitable buffer; b. Washing the Affinity column with suitable buffer; c. Optionally one more wash is performed with a suitable buffer; d. Eluting the protein mixture enriched with an antibody of interest with a suitable buffer having a concentration from about 100mM to about 200mM at suitable acidic pH; e. Performing the viral inactivation of eluted protein mixture (see claim 31).
The claims do not disclose performing neutralization of the eluted protein mixture or
wherein the neutralized protein mixture has turbidity lower than the protein mixture eluted with a buffer having a concentration below 100mM when measured with a standard turbidity meter, or wherein the neutralized protein mixture from step (e) is filtered using a 0.2 µm filter
Ramasubramanyan teaches performing neutralization of an eluted protein mixture after viral inactivation (see para. 0118, 0121).
The copending application and Ramasubramanyan are analogous invention in the art of protein purification. It would have been obvious to one skilled in the art to add the neutralization of Ramasubramanyan after the viral inactivation of the copending claims because it prepares the mixture for subsequent purification steps (see Ramasubramanyan para. 0118, 0121) and because it is the simple addition of a known treatment step to a known process, obviously resulting in the neutralization of the mixture, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). The combination does not explicitly teach “the neutralized protein mixture has turbidity lower than the protein mixture eluted with a buffer having a concentration below 100mM when measured with a standard turbidity meter”. However the turbidity is a result of the method, not an additional step. As the same method is disclosed the turbidity different is an inherent result.
Blaisdell teaches filtering a neutralized protein mixture after viral inactivation using a 0.2µm filter (see para. 0113).
The copending application and Blaisdell are analogous inventions in the art of protein processing. It would have been obvious to one skilled in the art to aa the filtration step of Blaisdell after the neutralization because it is the simple addition o f a known treatment step to a known mixture, obviously resulting in filtration of the eluted mixture, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.).
Regarding claims 10-13 and 19:
The claims of the copending application, as modified, disclose the process according to claim 1.
The claims are silent as to the elution buffer concentration and pH.
Ramasubramanyan teaches buffer concentrations of 100mM to 200mM, and 125mM (see para. 0120, 0192, 0278, 0281). Ramasubramanyan further teaches a pH of about 3.5 (0144, 0022).
It would have been obvious to one skilled in the art to select the buffer concentration of Ramasubramanyan for the elution of the copending application because they are result effective variables determining the final AR level (see Ramasubramanyan para. 0275). It would have been obvious to one skilled in the art to use the pH of about 3.0 or 3.5 because it is within a range suitable for virus inactivation, which is a desired goal of the copending claims (see Ramasubramanyan para. 0022). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re
Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding Claims 14-18:
Claims 14-18 of the instant invention correspond to claims 41-45 of the copending claims.
Regarding Claim 22:
The claims of the copending application, as modified, disclose the process according to claim 1.
Ramasubramanyan further teaches the affinity chromatography selected for Protein A or Protein G (see para. 0022).
It would have been obvious to one skilled in the art to replace the unspecified column of the copending invention with the Protein A or G column of Ramasubramanyan because itis the simple substitution of one known affinity column for another known affinity column, obviously resulting in the purification of the protein with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding Claims 23 and 24:
The claims of the copending application, as modified, disclose the process according to claim 1.
Ramasubramanyan further teaches wherein the elution buffer is selected from acetic acid (see para. 0212), Phosphoric acid, and HCl.
It would have been obvious to one skilled in the art to replace the unspecified buffer of the copending invention with the acetic acid of Ramasubramanyan because it is the simple substitution of one known buffer for another known buffer, obviously resulting in the purification of the protein with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 14-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49, 59, and 60 of copending Application No. 18/416,846 in view of Ramasubramanyan et al (US 2019/0062419) and Blaisdell (WO 2009/058769) .
Regarding Claim 1:
The claims of the copending application disclose process of purifying a protein mixture comprising; a. Loading the protein mixture of antibody or fragment thereof and impurities onto Affinity column with a suitable buffer; b. Washing the Affinity column with suitable buffer; c. Optionally one more wash is performed with a suitable buffer; d. Eluting the protein mixture enriched with an antibody of interest with a suitable buffer having a concentration from about 100mM to about 200mM at suitable acidic pH (see claim 49).
The claims do not disclose performing the viral inactivation of eluted protein mixture or neutralization of the eluted protein mixture or wherein the neutralized protein mixture has turbidity lower than the protein mixture eluted with a buffer having a concentration below 100mM when measured with a standard turbidity meter, or wherein the neutralized protein mixture from step (e) is filtered using a 0.2 µm filter.
Ramasubramanyan teaches performing viral inactivation and neutralization of an eluted protein mixture after viral inactivation (see para. 0118, 0121).
The copending application and Ramasubramanyan are analogous invention in the art of protein purification. It would have been obvious to one skilled in the art to add the viral inactivation and neutralization of Ramasubramanyan after the elution of the copending claims because it prepares the mixture for subsequent purification steps (see Ramasubramanyan para. 0118, 0121) and because it is the simple addition of a known treatment step to a known process, obviously resulting in the neutralization of the mixture, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). The combination does not explicitly teach “the neutralized protein mixture has turbidity lower than the protein mixture eluted with a buffer having a concentration below 100mM when measured with a standard turbidity meter”. However the turbidity is a result of the method, not an additional step. As the same method is disclosed the turbidity different is an inherent result.
Blaisdell teaches filtering a neutralized protein mixture after viral inactivation using a 0.2µm filter (see para. 0113).
The copending application and Blaisdell are analogous inventions in the art of protein processing. It would have been obvious to one skilled in the art to aa the filtration step of Blaisdell after the neutralization because it is the simple addition o f a known treatment step to a known mixture, obviously resulting in filtration of the eluted mixture, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.).
Regarding Claims 14-18:
Claims 24-18 of the instant application correspond to claims 59 and 60 of the copending application.
This is a provisional nonstatutory double patenting rejection.
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, 10-19 and 22-24 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 states “a pH of about 3.3 to about 3.5”. There is no support for a lower limit of “about 3.3”. The original disclosure only has support for a pH of about 3.0 and about 3.5.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 10, 11, 14 and 22-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giese et al (US 2019/0256556) in view of Blaisdell (WO 2009/058769).
Regarding Claim 1:
Giese teaches the process of purifying a protein, wherein the protein mixture comprise and antibody, or fragment thereof, and impurities, wherein the process comprises: a. Loading the protein mixture of antibody or fragment thereof and impurities onto an affinity column (Protein A load buffer); b. Washing the affinity column (protein A wash buffer); c. Optionally performing one or more wash; d. Eluting the protein mixture with an elution buffer, wherein the elution buffer has a concentration of 100mM to about 200mM (150mM) (see para. 0015) and a pH of about 3.3 to about 3.5 (pH 3.5) (see para. 0183)).
Giese does not explicitly teach Performing the viral inactivation and neutralization of eluted protein mixture in the same embodiment as eluting with a suitable buffer having a concentration from about 100mM to about 200mM, wherein when compared to a turbidity value, as measured by a standard turbidity meter, of a low salt protein mixture eluted with a low salt elution buffer having a concentration of less than 100 mM, the neutralized protein mixture has exhibits a turbidity value, as measured by a standard turbidity meter, that is lower, or wherein the neutralized protein mixture from step (e) is filtered using a 0.2 µm filter.
Giese further teaches Performing the viral inactivation (holding at pH less than 3.6 for 120 minutes) and neutralization (adjusting the pH to 5.0) of an eluted protein mixture (see para. 0465).
It would have been obvious to one skilled in the art to include the viral inactivation and neutralization of the eluted protein mixture of Giese with the buffer concentration between 100 and 200mM because it prepares the mixture for further processing (see para. 0465) and because it is the simple addition of known treatment steps to a known treatment process, obviously resulting in the destruction of viruses and neutralization of the mixture with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). Further both embodiments of Giese are directed to protein A columns. Giese does not explicitly teach that the turbidity of the neutralized protein mixture is less than a protein mixture eluted with a buffer having a concentration below 100mM. However, this limitation is interpreted as a characteristic of the protein mixture and not a required step of eluting a protein mixture with a buffer having a concentration below 100mM. As Giese teaches the same method steps the result of having a lower turbidity is inherently the same.
Blaisdell teaches filtering a neutralized protein mixture after viral inactivation using a 0.2µm filter (see para. 0113).
Giese and Blaisdell are analogous inventions in the art of protein processing. It would have been obvious to one skilled in the art before the effective filing date to add the filtering step of Blaisdell tot eh neutralized protein mixture of Giese because it is the simple addition of a known processing step to a known mixture, obviously resulting in filtration, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S.
__,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). Further Giese teaches filtration after chromatography (see Giese para. 0209)
Regarding Claim 10:
Giese teaches the process according to claim 1, wherein the elution buffer has a pH of about 3.5 (pH 3.5) (see para. 0183).
Regarding Claim 11:
Giese teaches the process according to claim 1wherein the elution buffer has a concentration of about 150mM and a pH of 3.5±0.1, and wherein the neutralized protein mixture exhibits a turbidity value of about 103 NTU (pH 3.5) (see Giese para. 0183). Giese does not explicitly teach the turbidity, however Giese teaches the same method steps and same material being treated as disclosed in the specification. Therefore the same result is presumed to be inherent (see MPEP 2112.01 II).
Giese does not teach wherein the suitable buffer concentration during elution step (d) is about 125mM.
Giese further teaches that the concentration of the buffers can be adjusted to reach the desired conductivity (see Giese para. 0162).
It would have been obvious to one skilled in the art before the effective filing date of the invention to adjust the buffer concentration and try a concentration of about 125mM because concentration is a result effective variable determining the conductivity of the column. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding Claim 14:
Giese teaches the process according to claim 1, wherein the antibody is selected from the group consisting of an IgGl antibody, or fragment thereof, IgG2 antibody, or fragment thereof; an IgG3 antibody ,or fragment thereof; an IgG4 antibody, or fragment thereof; antibody a fusion protein (see Giese para. 0324).
Regarding Claim 22:
Giese teaches the process according to claim 1, wherein the affinity column is Protein A (see Giese para. 0015 ) or Protein G.
Regarding Claim 23:
Giese teaches the process according to claim 1, wherein the elution buffer is acetic acid, phosphoric acid, or HCl (see Giese para. 0015).
Regarding Claim 24:
Giese teaches the process according to claim 1, wherein the elution buffer is acetic acid (see Giese para. 0015).
Claim(s) 12, and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giese et al (US 2019/0256556) and Blaisdell (WO 2009/058769) as applied to claim 1 above, and further in view of Luo et al, the article “Liquid-liquid phase separation causes high turbidity and pressure during low pH elution process in Protein A chromatography”.
Regarding Claim 12:
Giese teaches the process according to claim 1, wherein the elution buffer has a concentration of about 200mM and a pH of 3.5±0.1, and wherein the neutralized protein mixture exhibits a turbidity value of about 36.1 NTU (pH 3.5) (see Giese para. 0183). Giese does not explicitly teach the turbidity, however Giese teaches the same method steps and same material being treated as disclosed in the specification. Therefore the same result is presumed to be inherent (see MPEP 2112.01 II).
Giese does not teach wherein the suitable buffer concentration during elution step (d) is about 200mM.
Giese further teaches that the concentration of the buffers can be adjusted to reach the desired conductivity (see Giese para. 0162).
It would have been obvious to one skilled in the art before the effective filing date of the invention to adjust the buffer concentration and try a concentration of about 200mM because concentration is a result effective variable determining the conductivity of the column. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Giese does not explicitly teach wherein the elution buffer provides the turbidity in neutralized protein mixture of 36.1 NTU. Giese is silent as to the turbidity, however it would have been obvious to one skilled in the art to adjust the concentration of the elution buffer, and thereby the conductivity of the column (see para. 0162). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Adjusting the buffer concentration will inherently change the turbidity of the neutralized protein mixture.
Luo teaches that it is desirable to have a low turbidity in a column effluent (see Abstract) and that the buffer concentration effects the turbidity (see pgs. 62-63 section 3.5).
Giese and Luo are analogous inventions in the art of protein purification. It would have been obvious to one skilled in the art to adjust the buffer concentration, through routine experimentation, in Giese, thereby adjusting turbidity of the neutralized protein mixture, as disclosed by Luo, and reach a turbidity of 36.1 NTU because “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding Claim 13:
Giese teaches the process according to claim 1, wherein the elution buffer has a concentration of about 200mM and a pH of 3.5±0.1, and wherein the neutralized protein mixture exhibits a turbidity value of about 42.5 NTU (pH 3.5) (see Giese para. 0183). Giese does not explicitly teach the turbidity, however Giese teaches the same method steps and same material being treated as disclosed in the specification. Therefore the same result is presumed to be inherent (see MPEP 2112.01 II).
Giese does not teach wherein the suitable buffer concentration during elution step (d) is about 200mM.
Giese further teaches that the concentration of the buffers can be adjusted to reach the desired conductivity (see Giese para. 0162).
It would have been obvious to one skilled in the art before the effective filing date of the invention to adjust the buffer concentration and try a concentration of about 200mM because concentration is a result effective variable determining the conductivity of the column. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Giese does not explicitly teach wherein the elution buffer provides the turbidity in neutralized protein mixture of 42.5 NTU. Giese is silent as to the turbidity, however it would have been obvious to one skilled in the art to adjust the concentration of the elution buffer, and thereby the conductivity of the column (see para. 0162). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Adjusting the buffer concentration will inherently change the turbidity of the neutralized protein mixture.
Luo teaches that it is desirable to have a low turbidity in a column effluent (see Abstract) and that the buffer concentration effects the turbidity (see pgs. 62-63 section 3.5).
Giese and Luo are analogous inventions in the art of protein purification. It would have been obvious to one skilled in the art to adjust the buffer concentration, through routine experimentation, in Giese, thereby adjusting turbidity of the neutralized protein mixture, as disclosed by Luo, and reach a turbidity of 42.5 NTU because “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Claim(s) 15 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giese et al (US 2019/0256556) and Blaisdell (WO 2009/058769) as applied to claim 14 above, and further in view of Gagnon (WO 2013180647)
Regarding Claim 15:
Giese teaches the process according to claim 14.
Giese does not teach the isoelectric point of the protein.
Gagnon teaches an IgG1 antibody of fusion protein with an isoelectric point from 6 to 9 (pi 8.45) (see para. 00233).
Giese, as modified, and Gagnon are analogous inventions in the art of protein purification. It would have been obvious to one skilled in the art to replace the protein of Giese with the protein of Gagnon, such that the isoelectric point is from 6 to 9 because it is the simple substitution of one known IgG1 protein with another IgG1 protein, obviously resulting in purification, with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflexinc., 550 U.S.__,__, 82 USPQ2d 1385, 1395 —97 (2007) (see MPEP § 2143, B.).
Regarding Claim 16:
Giese, as modified, teaches the method of claim 14.
Giese does not explicitly teach any of the antibodies or fusion proteins claimed.
Gagnon teaches an IgG1 antibody or fusion protein selected from Trastuzumab (see para. 00233).
Giese, as modified, and Gagnon are analogous inventions in the art of protein purification. It would have been obvious to one skilled in the art to replace the protein of Giese with the protein of Gagnon, because it is the simple substitution of one known IgG1 protein with another IgG1 protein, obviously resulting in purification, with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex |Inc.,550 U.S. ,_—, 82 USPQ2d 1385, 1395 —97 (2007) (see MPEP § 2143, B.).
Claim(s) 17 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giese et al (US 2019/0256556) and Blaisdell (WO 2009/058769) as applied to claim 1 above, and further in view of Hsiung et al (WO 2013096791).
Regarding Claim 17:
Giese, as modified, teaches the process according to claim 1.
Giese does not explicitly teach that the IgG1 antibody binds to IgE (anti-IgE antibody).
Hsiung teaches purifying a protein that binds to IgE (see pg. 14 lines 16-20).
Giese and Hsiung are analogous inventions in the art of protein purification. It would have been obvious to one skilled in the art before the effective filing date to replace the IgG1 of Giese with an anti-IgE antibody, because it is known that proteins can bind with IgE (see Hsiung pg. 14 lines 16-20) and through routine experimentation one skilled in the art would have found appropriate antibodies to purify with the known method.
Regarding Claim 18:
Giese, as modified, teaches the process according to claim 17, wherein the anti-IgE
antibody is Omalizumab (see Hsiung pg. 14 lines 16-20).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Giese et al (US 2019/0256556) and Blaisdell (WO 2009/058769) as applied to claim 1 above, and further in view of Hsiung et al (WO 2013096791).
Regarding Claim 19:
Giese teaches the process according to claim 1.
Giese does not teach that the antibody is omalizumab.
Hsiung teaches purifying a protein mixture that contains omalizumab (see pg. 14 lines 16-20).
Giese and Hsiung are analogous inventions in the art of protein purification. It would have been obvious to one skilled in the art before the effective filing date to replace the IgG1 of Giese with omalizumab, because it is the simple substitution of one known protein with another known protein, obviously rousting in purification, with an expectation of success.
Giese does not teach wherein the suitable buffer concentration during elution step (d) is about 200mM.
Giese further teaches that the concentration of the buffers can be adjusted to reach the desired conductivity (see para. 0162).
It would have been obvious to one skilled in the art before the effective filing date of the invention to adjust the buffer concentration and try a concentration of about 200mM because concentration is a result effective variable determining the conductivity of the column. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Conclusion
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/CLAIRE A NORRIS/Primary Examiner, Art Unit 1779 12/8/2025