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 .
Claims 1,8-16,18-19 are under examination.
Claim Objections
The term “media” has been changed to –medium--. Therefore, the former claim objection has been removed.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 12-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant) regards as the invention.
Claim 12 recites, “wherein providing the level of (poloxamer 188) comprises removing poloxamer 188 from the mammalian cell culture.” This is indefinite because “providing” means that you are giving a specific substance; however, “removing” means that it is being taken away. The two are opposites. It is unclear how the non-ionic surfactant can be provided and taken away at the same time. It is not clear how the removing occurs. Is the poloxamer 188 removed from the actual filter, does the poloxamer stay on the filter, does the poloxamer go into the filtrate.
Claims 13-16 recites that the cell culture medium is concentrated. It is not clear if the cell culture medium is concentrated before nanofiltration, during filtration, or after filtration. The claim limitation states that the cell culture medium is concentrated but it does not even offer a comparison of a baseline that it is being compared to. It is not clear if applicant means “concentrated” to refer to the amount of growth factor or another type of medium component.
Response to Applicants Arguments
The amendment made to the independent claim 1 has provided some clarity for the claimed invention. Therefore, the rejections involving claims 1,8-11 are removed.
Claim 12 is still indefinite because it recites that providing poloxamer 188 is removing poloxamer 188. This is contradictory and indefinite language. Applicants further argue, that “achieving a particular concentration in the culture medium can be done by either adding/providing or removing surfactant…” There is no mention in claim 12 of adjusting a concentration by manipulating the level of surfactant present. Adding/providing and removing are two separate methods; they can both be present in the claim language as long as they are distinct operations.
Claim 13 and its dependent claims state that the medium is a concentrate. The claims fail provide detail concerning what the term “concentrate” means. When reading the claims, It is unclear how the medium differs from another medium containing 0.1 g/L to less than 1 g/L of poloxamer 188. It is also unclear if applicants mean that specific factors or agents within the medium are concentrated before or after filtration. There is no mention of any components of the culture medium being adjusted or diluted in the instant set of claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1,8-9,11,13-16,18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Pol (US 20070065907)
Pol teaches a method of nanofiltering mammalian cell culture medium (Pages 1-2), the method comprising: providing a level of non-ionic surfactant (the amount of non-ionic surfactant is at least 0.001 w/w% to 1 w/w% as taught in Paragraphs 5 and 7 of Pol, equivalent to .01 g/L to 10 g/L) in a quantity of mammalian cell culture media comprising a growth factor (Paragraph 19 of Pol). Pol teaches a range of non-ionic surfactant that encompasses the claimed range. Pol teaches wherein the non-ionic surfactant comprises polaxmer 188 (Pluronic F68). Pol teaches a range of non-ionic surfactant that encompasses the range used by applicant. In Pol’s system, approximately 100% of the cells are retained by the filter and the growth factors can be concentrated in the filtrate after filtering (Example 1 of Pol). Because Pol teaches the same method as applicant using a non-ionic surfactant at the same concentration to concentrate and retain the desired target growth factor, one would be expect that at least 60% of the growth factor taught in Pol would be retained in the filtrate solution as in instant Claims 1,8-9.
MPEP § 2144.05 (II) states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[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.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”)
A review of the specification fails to provide evidence that the claimed concentrations and volumes of cell culture mediums are critical. Absent such evidence it would have been obvious to an artisan of ordinary skill at the time of effectively filing Pol to try a finite number of possible concentrations of cell culture medium and desirable volume of the culture medium. An artisan would have a reasonable expectation of success in optimizing the concentrations of cell culture medium and cell culture medium volume because determining these parameters were already known to be optimizable as demonstrated by Pol. Thus, Pol renders to concentration and volume of the cell culture medium. Furthermore, since Pol’s teaches the same nanofiltration with the same concentration of non-ionic surfactant, it would be expected to produce the same results as claimed as in instant Claims 9,13-16. Pol teaches wherein providing the level of non-ionic surfactant comprises adding non-ionic surfactant to the mammalian cell culture (Example 1, Paragraph 22) and where the mammalian cells can produce a monoclonal antibody (a protein) as in instant claims 11,17-19.
Pol teaches treating a cell culture medium with a non-ionic surfactant in order to improve the ability to retain target growth factors using nanofiltration. Pol teaches a broad range of non-ionic surfactants that can be successfully added to cell culture medium. It would be expected that an artisan of ordinary skill in the art would have adjusted the non-ionic surfactant concentration in order to successfully retain as much of the growth factor as desired. Given the teachings of the cited references and the level of skill of an ordinarily skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the clamed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be high educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature. These people will have practical knowledge in molecular biology and nanofiltration. Therefore, the level of ordinary skill in this art is high.
Response to Applicants Arguments/Amendments
Applicants argue, that Pol’s filtration cited by examiner in the rejection differs from applicant’s nanofiltration because Pol just teaches a filtration process that uses a spin filter with a mesh size of 325 x 2300 (Paragraph 22 of Pol). Applicants argue that a “nanofilter is a filter suitable for excluding viruses from the filtrate and may have an effective pore size of 22 mm or less.” Applicants further argue that Pol’s spin filter is designed for cell retention, retaining cells while allowing biological substances including viruses to pass through without removing viruses…and that the pores in the mesh of Pol’s filter are just designed to retain mammalian cells.
Nano technology/nanofiltering includes filtering medium from substances such as mammalian cells (which are small) and collecting the factors (small in size) produced in the culture and present in filtrate as taught in Pol. The argument directly above is not commensurate in scope with the instant set of claims. The claims do not mention viruses at all in the instant claims. The pore size of a filter is not mentioned in the instant claims. The addition of such limitations to the instant claims could help distinguish the claim language from the prior art cited in the rejections. If the pore size of Pol is actually larger than the pore size of applicants’ invention, it would allow more factors to pass through. Thus the limitation, “whereby at least 60% of the growth factor is retained in the cell culture medium following said nanofiltering” is taught by Pol.
Claims 1,8-11,13-16,18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Pol (US 20070065907) in view of Romand “Improving Expression of Recombinant Human IGF-1 Using IGF-1R Knockout CHO Cell Lines” Biotechnology and Bioengineering, Vol 113, No. 5, May 2016.
Pol applies as above to teach claims1,8-9,11,13-16,18-19. Pol fails to teach filtering out and retaining IGF-1. Pol does teach that target factors can be produced by cells such as (Chinese Hamster Ovary Cells) (Paragraphs 13 and 19 of Pol). Pol does not teach that CHO cells can produce IGF-1. However, Romand teaches that IGF-1 can be produced by CHO cells (Abstract). It would have been obvious to an artisan of ordinary skill in the art to have produced IGF-1 using CHO cells. An artisan would have been motivated to have filtered out IGF-1 (a growth factor) of interest because it is known that IGF-1R Knockout CHO lines can produce high levels of IGF-1 (Abstract). IGF-1 is valuable because it a therapeutic hormone (Page 1 of Romand. Because such cells can produce high titers of IGF-1, there would have been a high expectation for success (Abstract of Romand) as in instant Claim 10.
Pol teaches treating a cell culture medium with a non-ionic surfactant in order to improve the ability to factor out target factors using nanofiltration. Pol teaches a broad range of non-ionic surfactants that can be successfully added to cell culture medium. It would be expected that an artisan of ordinary skill in the art would have adjusted the non-ionic surfactant concentration in order to successfully retain as much as the target molecule/growth factor as desired. CHO cells, taught in Pol, are known to have the ability to produce growth factors/proteins of interest. An artisan would have been motivated to have produced IGF-1 using CHO cells as taught in Romand since it is known that CHO cells can be appropriately modified to produce high titers of IGF-1. IGF-1 is a valuable pharmaceutical hormone. Given the teachings of the cited references and the level of skill of an ordinarily skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the clamed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be high educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature. These people will have practical knowledge in molecular biology and nanofiltration. Therefore, the level of ordinary skill in this art is high.
Response to Applicants arguments
Applicants argue that Romand fails to cure the deficiencies of Pol. Because Pol is not deficient, Romand is not a defective reference.
Conclusion
All claims stand rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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