DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the claims
The amendment filed 03/19/26 is acknowledged and has been entered. New claims 13-18 have been added. Claims 2-7 were previously canceled. Accordingly, claims 1 and 8-18 are pending and under examination.
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.
Claims 1 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (US 2008/0261249) in view of Hickman et al (US 2014/0255423).
Wang et al discloses a method of producing a polyclonal anti-host cell antibody preparation and discloses that the method comprises acquiring a sample from an animal that has been immunized with HCP wherein the sample comprises polyclonal antibodies generated against host cell proteins (HCP) (e.g. para’s 0031-0034, 0051-0053). Wang et al discloses purifying the sample by contacting the sample with a HCP affinity chromatography column (e.g. para’s 0033-0034, 0054-0057). Wang et al discloses that the capture antibodies are eluted and treated (concentrated) and that this process can be done again by flowthrough (e.g. para 0034, 0054-0057). Wang et al discloses that the affinity column comprises HCP immobilized to beads (substrate) and discloses that the HCP is coupled to CNBr-derivatized substrate (e.g. 0054-0055).
Wang et al differs from the instant invention in failing to teach the use of protein A to provide an antibody preparation before the step of separating with HCP coupled to a substrate. Wang et al also fails to explicitly teach the steps of diafiltration.
Hickman et al teaches methods for producing a purified (or HCP-reduced) antibody preparation and teaches that it is known in the art that a step of affinity chromatography wherein protein A is utilized prior to subsequent purification steps (e.g. para’s 0006, 0085, 0087, 0094-0098, 0117-0120). Hickman et al also teaches that it is known and conventional in the art to use diafiltration and teaches that diafiltration is a method of using ultrafilters to remove and exchange salts, sugars and on-aqueous solvents, to separate free from bound species, to remove low molecular-weight materials. Hickman also teaches that a diafiltration step is employed to exchange various buffers and can be used prior to further purification steps, as well as to remove impurities from antibody preparations (e.g. para’s 0107-0108, 0123, 0129).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate a step of affinity purification utilizing protein A to separate the antibodies in the method of Wang et al before the step of purification with HCP coupled to the substrate because Hickman et al shows that it is known and conventional to provide a step of affinity purification wherein protein A is utilized prior to subsequent purification steps to provide a purified sample of antibodies and Wang et al specifically teaches that further purification of the crude anti-HCP antibodies may be required (e.g. 0033). Further, it would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate a step of affinity purification utilizing protein A to separate the antibodies in the modified method of Wang because Hickman teaches that it is known that protein A can be utilized as a reagent to provide purified antibodies and one of ordinary skill in the art would recognize that additional purification steps would provide for a more purified sample. It has long been held that it is obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating a step of affinity purification utilizing protein A to separate the antibodies in the method of Wang et al before the step of purification with HCP coupled to the substrate.
It would have also been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate diafiltration steps after contacting with protein A affinity reagent and also after isolating the anti-HCP antibody because Hickman teaches that it is known and conventional in the art to use diafiltration and teaches that diafiltration is a method of using ultrafilters to remove and exchange salts, sugars and on-aqueous solvents, to separate free from bound species, to remove low moleculear-weight materials. Hickman also teaches that a diafiltration step is employed to exchange various buffers and can be used prior to further purification steps, as well as to remove impurities from antibody preparations. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating diafiltration steps after contacting with protein A affinity reagent and also after isolating the anti-HCP antibody. Therefore, absent evidence to the contrary it would also have been obvious to have the modified method of Wang et al consist of these steps for the purification.
With respect to the recitation “wherein the polyclonal anti-HCP antibody preparation contains no more than 50% non-HCP specific IgGs”. Since the combination of Wang et al., and Hickman et al. teach method steps and reagents consonant to the instantly recited claims it is deemed that in the modified method of Wang et al that the method would remove at least 50% non-HCP specific IgGs and contain no more than 50% non-HCP specific IgGs.
Claims 1 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (US 2008/0261249) in view of Prakash et al., (Analytical Methods for the Measurement of Host Cell Proteins and Other Process-Related Impurities, American Chemical Society, October 2015, Chapter 9, pages 387-404) and further in view of Hickman et al (US 2014/0255423).
Wang et al discloses a method of producing a polyclonal anti-host cell antibody preparation and discloses that the method comprises acquiring a sample from an animal that has been immunized with HCP wherein the sample comprises polyclonal antibodies generated against host cell proteins (HCP) (e.g. para’s 0031-0034, 0051-0053). Wang et al discloses purifying the sample by contacting the sample with a HCP affinity chromatography column (e.g. para’s 0033-0034, 0054-0057). Wang et al discloses that the capture antibodies are eluted and treated (concentrated) and that this process can be done again by flowthrough (e.g. para 0034, 0054-0057). Wang et al discloses that the affinity column comprises HCP immobilized to beads (substrate) and discloses that the HCP is coupled to CNBr-derivatized substrate (e.g. 0054-0055).
Wang et al differs from the instant invention in failing to teach the use of protein A to provide an antibody preparation before the step of separating with HCP coupled to a substrate. Wang et al also fails to explicitly teach the steps of diafiltration.
Prakash et al teaches methods of making Anti-HCP polyclonal antibody preparation wherein the antibody preparation has been purified (e.g. pages 394-395). Prakash et al discloses that an animal such as a goat or sheep is immunized with HCP obtained from mammalian cells (e.g. pages 394-395). Prakash et al discloses that a sample is collected from the animal and antibody purification is performed by using a combination of Protein A with HCP column affinity chromatography (substrates) (e.g. pages 394-395). Prakash et al discloses that the mammalian cells can be CHO cells (e.g. page 388, 394).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate a combination of Protein A with HCP column affinity chromatography (substrates) such as taught by Prakash for purification in the method of Wang because Prakash teaches that it is known and conventional in the art. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating a combination of Protein A with HCP column affinity chromatography (substrates) such as taught by Prakash for purification in the method of Wang.
Wang et al and Prakash et al differ from the instant invention in failing teach the steps of diafiltration.
Hickman et al teaches that it is known and conventional in the art to use diafiltration and teaches that diafiltration is a method of using ultrafilters to remove and exchange salts, sugars and on-aqueous olvents, to separate free from bound species, to remove low moleculear-weight materials. Hickman also teaches that a diafiltration step is employed to exchange various buffers and can be used prior to further purification steps, as well as to remove impurities from antibody preparations (e.g. para’s 0107-0108, 123, 0129).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate diafiltration steps after contacting with protein A affinity reagent and also after isolating the anti-HCP antibody because Hickman teaches that it is known and conventional in the art to use diafiltration and teaches that diafiltration is a method of using ultrafilters to remove and exchange salts, sugars and on-aqueous solvents, to separate free from bound species, to remove low molecular-weight materials. Hickman also teaches that a diafiltration step is employed to exchange various buffers and can be used prior to further purification steps, as well as to remove impurities from antibody preparations. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating diafiltration steps after contacting with protein A affinity reagent and also after isolating the anti-HCP antibody. Therefore, absent evidence to the contrary it would also have been obvious to have the modified method of Wang et al consist of these steps for the purification.
With respect to the recitation “wherein the polyclonal anti-HCP antibody preparation contains no more than 50% non-HCP specific IgGs”. Since the combination of Wang et al., Prakash et al and Hickman et al teach method steps and reagents consonant to the instantly recited claims it is deemed that in the modified method of Wang et al that the method would remove at least 50% non-HCP specific IgGs and contain no more than 50% non-HCP specific IgGs.
Claims 8-9 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al in view of Hickman et al as applied to claim 1 above, and further in view of Chimento et al., (Genetic Engineering and Biotechnology News, January 27, 2014, pages 1-7).
See above for the teachings of Wang et al., and Hickman et al.,
Wang et al., and Hickman et al., differ from the instant invention in failing to teach the animal immunized is a sheep or goat.
Chimento et al teaches that it is known and conventional in the art that anti-HCP antibodies can be produced by animal immunization in animals such as rabbits, sheep or goats (rabbit is the animal utilized in Wang) (e.g. page 4).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate a sheep or goat for the rabbit in Wang et al for producing the antibodies because Chimento et al shows that it is known and conventional in the art to utilize a goat, sheep or rabbit for producing polyclonal HCP antibodies. Thus, absent evidence to the contrary one of ordinary skill in the art would have a reasonable expectation of success incorporating a sheep or goat for the rabbit in Wang et al for producing the antibodies.
Claims 8-9 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al in view of Prakash et al and Hickman et al as applied to claim 1 above, and further in view of Chimento et al., (Genetic Engineering and Biotechnology News, January 27, 2014, pages 1-7).
See above for the teachings of Wang et al., Hickman et al., and Prakash et al.
Wang et al., Hickman et al., and Prakash et al differ from the instant invention in failing to teach the animal immunized is a sheep or goat.
Chimento et al teaches that it is known and conventional in the art that anti-HCP antibodies can be produced by animal immunization in animals such as rabbits, sheep or goats (rabbit is the animal utilized in Wang) (e.g. page 4).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate a sheep or goat for the rabbit in Wang et al for producing the antibodies because Chimento et al shows that it is known and conventional in the art to utilize a goat, sheep or rabbit for producing polyclonal HCP antibodies. Thus, absent evidence to the contrary one of ordinary skill in the art would have a reasonable expectation of success incorporating a sheep or goat for the rabbit in Wang et al for producing the antibodies.
Claims 10 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al in view of Hickman et al and Chimento et al as applied to claims 1 and 8-9 above, and further in view of Krawitz et al (Proteomics 2006, 9, pages 94-110) (submitted in the IDS filed 05/03/22).
See above for the teachings of Wang et al., Hickman et al., and Chimento et al.
Wang et al., Hickman et al and Chimento et al differ from the instant invention in failing to teach the host cell is a CHO cell.
Krawitz et al teaches that it is known and conventional in the art that antibodies are raised against CHO cell protein mixtures (e.g. abstract, page 95).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the use of CHO cells as host cells in the modified method of Wang et al because Krawitz et al shows that it is known and conventional in the art that CHO cells can be utilized in biopharmaceuticals and utilized to raise antibodies against host cell proteins of the CHO cells. Thus, absent evidence to the contrary one of ordinary skill in the art would have a reasonable expectation of success incorporating the use of CHO cells as host cells in the modified method of Wang et al.
Claims 10 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al in view of Prakash et al., Hickman et al and Chimento et al as applied to claims 1 and 8-9 above, and further in view of Krawitz et al (Proteomics 2006, 9, pages 94-110) (submitted in the IDS filed 05/03/22).
See above for the teachings of Wang et al., Prakash et al., Hickman et al and Chimento et al.
Wang et al., Prakash et al., Hickman et al and Chimento et al differ from the instant invention in failing to teach the host cell is a CHO cell.
Krawitz et al teaches that it is known and conventional in the art that antibodies are raised against CHO cell protein mixtures (e.g. abstract, page 95).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate the use of CHO cells as host cells in the modified method of Wang et al because Krawitz et al shows that it is known and conventional in the art that CHO cells can be utilized in biopharmaceuticals and utilized to raise antibodies against host cell proteins of the CHO cells. Thus, absent evidence to the contrary one of ordinary skill in the art would have a reasonable expectation of success incorporating the use of CHO cells as host cells in the modified method of Wang et al.
Claims 11-12 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al in view of Hickman et al., Chimento et al and Krawitz et al as applied to claims 1, and 8-10 above, and further in view of Still et al (US 6,797,522).
See above for the teachings of Wang et al., Hickman et al., Chimento et al and Krawitz et al.
Wang et al., Hickman et al., Chimento et al and Krawitz et al differ from the instant invention in failing to teach the substrate is derivatized with NHS.
Still et al teaches that it is known in the art that either CNBr-derivatized or NHS derivatized substrates can be utilized in affinity chromatography (e.g. para col 13, lines 9-13).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate NHS derivatized substrates such as taught by Still et al into the modified method Wang et al because Still et al shows that it is known and conventional in the art. Thus, absent evidence to the contrary one or ordinary skill in the art would have a reasonable expectation of success incorporating NHS derivatized substrates such as taught by Still et al into the modified method Wang et al.
With respect to claims 12 as currently recited. Since the combination of Wang et al., Hickman et al., Chimento et al., Krawitz et al and Still et al teach method steps and reagents consonant to the instantly recited claims it is deemed that in the modified method of Wang et al that the method would contain no more than 40% non-HCP specific IgGs.
Claims 11-12 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al in view of Prakash et al., Hickman et al., Chimento et al and Krawitz et al as applied to claims 1, and 8-10 above, and further in view of Still et al (US 6,797,522).
See above for the teachings of Wang et al., Prakash et al., Hickman et al., Chimento et al and Krawitz et al.
Wang et al., Prakash et al., Hickman et al., Chimento et al and Krawitz et al differ from the instant invention in failing to teach the substrate is derivatized with NHS.
Still et al teaches that it is known in the art that either CNBr-derivatized or NHS derivatized substrates can be utilized in affinity chromatography (e.g. para col 13, lines 9-13).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate NHS derivatized substrates such as taught by Still et al into the modified method Wang et al because Still et al shows that it is known and conventional in the art. Thus, absent evidence to the contrary one or ordinary skill in the art would have a reasonable expectation of success incorporating NHS derivatized substrates such as taught by Still et al into the modified method Wang et al.
With respect to claims 12 as currently recited. Since the combination of Wang et al., Prakash et al., Hickman et al., Chimento et al., Krawitz et al and Still et al teach method steps and reagents consonant to the instantly recited claims it is deemed that in the modified method of Wang et al that the method would contain no more than 40% non-HCP specific IgGs.
Response to Arguments
Applicant's arguments filed 03/19/26 have been fully considered but they are not persuasive.
Applicant argues that the combination of Wang and Hickman would not render claim 1 obvious, at least because one of skill in the art would not be motivated to combine the disclosures because Wang describes that there is no significant improvement in the binding activity of the protein A purified anti-HCP antibody over the crude antiserum (e.g. para 0061).
This argument is not found persuasive because it appears that the Applicant is arguing that Wang is teaching away from a protein A purification step and this is not found persuasive because Wang et al also specifically teaches that the anti-HCP antibodies are collected and may require purification by known methods in the art (e.g. para 0033). Thus, one of ordinary skill in the art would look to known methods of purification to be added to the method of Wang et al. Further, it is well settled that a reference must be evaluated for all disclosures not just its preferred embodiments. In re Mills, 470 F. 2d 649, 176 USPQ 196 (CCPA 1972). Therefore, Wang et al does not teach away from the use of purification but actually teaches additional purification may be required. Further, although Wang may teach no significant improvement, Wang does not teach a detriment or that there is no improvement.
Applicant argues that Hickman describes that use of protein A affinity chromatography may not always be advantageous such as in the context of the purification of IgG3 antibodies and the absence of an Fc region (e.g. para 0087).
This argument is not found persuasive because the instant claims are not limited to IgG3 antibodies and as disclosed by Hickman (e.g. 0094) Protein A is useful for affinity purification of IgG1, IgG2, and IgG4, and Wang et al teaches the antibody can be IgG1 or IgG4). Hickman et al specifically teaches that one tailors the purification (e.g. para 0087) and thus one would use the appropriate purification reagent accordingly such as using protein A with IgG1, IgG4 as taught in Wang.
Applicant further argues that Prakash does not describe advantages of using protein A affinity chromatography and that Prakash describes that Protein A can become a process-related impurity.
This argument is not found persuasive because Prakash specifically teaches that with Protein A the rule of thumb that is followed is to develop and optimize processes to bring all process-related impurities as low as a level as possible. Thus, Prakash is teaching to optimize the purification. Further, Prakash explicitly shows that antibody purification can be carried out with a combination of Protein A and HCP column affinity chromatography. Prakash in fact discloses that the purification is usually carried out in the manner (e.g. page 395). Therefore, one of ordinary skill would look to combine Protein A with HCP column affinity and would have a reasonable expectation of success.
Conclusion
No claims are allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678