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 1-14, 16-29, and 31-35 are canceled.
Claim 36 is new.
Claim 15 is amended.
Claims 15, 30, and 36 are pending and under examination on the merits.
Priority
Acknowledgment is made of applicant’s claim to priority under 35 U.S.C. 119 (a)-(d). The certified copy of the foreign priority application, filed 05/24/2018, has been filed in the international stage of PCT/FR2019/051195.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 15, 30, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2012017156 A1, (published 02/09/2012), hereinafter referred to as Huille, in view of Kiovig (Kiovig : EPAR - Scientific Discussion, https://www.ema.europa.eu/en/documents/scientific-discussion/kiovig-epar-scientific-discussion_en.pdf (published and last updated on 03/22/2006 (as evidenced by Screenshot appended to the Office Action set)).
Regarding claims 15, Huille teaches a liquid pharmaceutical composition (see claim 1) intended for subcutaneous administration (see abstract), which are aqueous/liquid solutions of IgG compositions directly obtained by fractionation of human plasma (human IgG) (see for example, the manufacturing process section at, for example, pg. 4/16-and example 2). The aqueous medium is composed of water for injection (PPI water) which may contain pharmaceutically acceptable excipients and is compatible with IgG (see for example, the manufacturing process section at pg. 4/16 and example 2), having IgG at concentrations ranging from 230-350g/L (see for example, claim 18), 200g/L (see for example, page 3/16), and 160g/L (see for example, page 3/16 and Example 4 at pg. 11/16). The composition of Huille further comprises glycine at a concentration of 200-300mM (see for example, claim 3 of Huille) and nonionic detergent at a concentration of less than 40ppm (see for example, claim 12) at a pH of 4.2-5.5 (see for example, claim 16). Huille additionally teaches the composition wherein the nonionic detergent is selected from the group consisting of polysorbates and poloxamers (see for example, claim 9) [which may be polysorbate 80; see for example, page 5/16 of the English Translation of Huille WO2012017156A1; see also for example, claim 10 of Huille].
Further guiding one of ordinary skill in the art to the formulation of Huille comprising lower concentrations (20ppm or less) of nonionic detergent, Kiovig teaches therapeutic formulations of Kiovig (a human IgG antibody) at 100mg/ml (100 g/L) (see for example, the first sentence of the first paragraph of the Description and Composition section at page 4/23). Kiovig goes on to teach that literature on the solvents/detergents used in the manufacture of Kiovig support safety and efficacy of the claimed polysorbate 80 concentration where the measured level of the detergent in the lots was <20ppm for polysorbate 80 (see for example, the paragraph beneath the other toxicity studies bullet point on pg. 12/23).
Huille does not specifically teach the specific glycine concentrations of claim 15; the specific nonionic detergent concentrations of claim 15; or the more narrow range of recited pH values of claim 15; however, Applicant’s attention is drawn to MPEP 2144.05(I),
“In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In reWertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In reWoodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of “about 1-5%” while the claim was limited to “more than 5%.” The court held that “about 1-5%” allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of “50 to 100 Angstroms” considered prima facie obvious in view of prior art reference teaching that “for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms].” The court stated that “by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.”)… Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)… A range can be disclosed in multiple prior art references instead of in a single prior art reference depending on the specific facts of the case. Iron Grip Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1322, 73 USPQ2d 1225, 1228 (Fed. Cir. 2004).”
Applicant’s attention is further drawn to MPEP 2144.05(II)(A), Routine Optimization - Optimization Within Prior Art Conditions or Through Routine Experimentation:
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 re Aller, 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 re Hoeschele, 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 re Kulling, 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.”).
Although this passage does not specifically point to, for example, compositions of immunoglobulins, this passage points to numerous variables that affect the function of inventions, such as concentration of reagents and pH ranges. Furthermore, this passage indicates that the optimization of such variables is often obvious activity for one of ordinary skill in the art. It is submitted that the claimed concentrations of IgG, nonionic detergent, and glycine, as well as the claimed pH ranges, are akin to the variables discussed in the cited MPEP passage, because said concentrations and ranges are optimizable variables that would affect at least the toxicity and/or efficacy and/or stability, i.e., function, of the claimed invention. Given the “normal desire of scientists or artisans to improve upon what is already generally known,” it would have been prima facie obvious to one of ordinary skill in the art to optimize the claimed glycine and nonionic detergent concentrations and pH, because such optimization would produce a more effective invention.
Also, as set forth in MPEP 2144.05(II)(B), There is a Motivation to Optimize Result-Effective Variables:
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding. In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that “obvious to try” was a valid rationale for an obviousness finding, for example, when there is a “design need” or “market demand” and there are a “finite number” of solutions. 550 U.S. at 421 (“The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a personal of ordinary skill in the art to experiment to reach another workable product or process.
In the instant case, the claims are drawn to particular compositions comprising different concentrations of IgG, nonionic detergent, and glycine, as well as specified pH ranges, and each of these variables achieves a recognized result, such as drug toxicity, therapeutic benefit, and/or reduced aggregation. Accordingly the recited concentrations and ranges are result-effective variables encompassed within the art-disclosed ranges that achieve a recognized result, such as stability/reduced aggregation, and it is submitted that since one of ordinary skill in the art would have thus been motivated to determine the optimum or workable ranges of said variables, the concentrations of components of the composition and pH ranges recited were prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention as result effective variable for optimization wherein any concentration within the art disclosed ranges would have been obvious to try (see MPEP section 2143).
Regarding claim 30, the instant application recites the composition of claim 15, wherein the IgG is obtained by fractionation of blood plasma. Huille teaches the composition having “IgG…obtained by fractionation of human plasma,” (see for example, page 7 of the specification, paragraph 3). Therefore, the invention of Huille meets the limitation of the instant claims 30.
Regarding claim 36, as discussed above, Huille in view of Kiovig teaches and makes obvious a composition meeting the broadest reasonable interpretation recited by instant claim 15.
Huille and Kiovig do not explicitly state that the osmolality is about 340 mOsm/kg.
However, the artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references, whereupon all of the limitations of instant claim 15 would have been met upon said combination where the resulting composition would be presumed to have an osmolality of about 340 mOsm/kg given that function and properties necessarily flow from the components/structures required.
Applicant’s Arguments:
Applicant argues that the cited references do not teach 200g/L +/-5% (190-210g/L).
Response: The Examiner discusses Huille’s teaching of a composition comprising acceptable excipients and is compatible with IgG (see the manufacturing process section at pg. 4/16 and example 2), having IgG at concentrations ranging from 230-350g/L (see claim 18), 200g/L (see page 3/16), and 160g/L (see page 3/16 and Example 4 at pg. 11/16). Applicant notes that the 200g/L IgG is of a commercial embodiment. It is noted that the artisan reading the entirety of Huille would have understood Huille to teach the 200g/L as being compatible for use in the formulation. There would be no other logical reasons for Huille to specifically mention this concentration which happens to fall within the range of IgG. Huille makes obvious for use in the composition (230-160g/L IgG). The MPEP provides that:
“A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)… Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971),”
(see MPEP section 2123(I-II)).
Therefore, this argument is unpersuasive.
B. Applicant reiterates their traversal of the position that Huille teaches a composition having 40ppm or less of nonionic detergent.
Response: This argument remains unpersuasive. Applicant cherry-picks citations from Huille to support their position. Applicant’s citations, notably, are also to preferred embodiments of Huille and do not preclude or teach away from a composition having less than 40ppm nonionic detergent. Applicant continues to fail to appreciate that Huille discloses that:
“[s]tep d) of the method according to the invention may comprise one or more surfactants, for example of the non-ionic detergent type…[t]he concentration of non-ionic detergent sufficient to stabilize the composition according to the invention is preferably between 0 and 1000 ppm, preferably between 0 and 300 ppm, preferably between 0 and 50 ppm.The addition of the surfactant in step d makes it possible to avoid the phenomenon of aggregation of the composition.”
(see Huille, pages 5-6). Wherein the amount of surfactant added in step d is preferably 0-50ppm, evidencing that Huille clearly contemplated, in fact, preferred embodiments where no surfactant was added in step d, such that the amount added in step b, 40ppm of surfactant or less, may very well embody the final concentration of surfactant/non-ionic detergent present in the final composition. Claim 12 of Huille points to preferably adding less than 40ppm of surfactant in step b, when combined with the cited text above which teaches that preferably 0-50ppm of surfactant are added in step d (with steps b and d being the only steps directed to adding surfactants, it is clear that a final product having less than 40ppm surfactant total is an embodiment not only contemplated by, but even given preference by the cited teachings of Huille. This is further supported by the following language in Huille, “Advantageously, the surfactant added in step b) and/or d) is preferably a non-ionic detergent,” at paragraph 0031 of the English translation in US20130121991 A1). For these reasons, the Examiner finds the Applicant’s argument that Huille does not teach a composition having 40ppm non-ionic detergent or less to be unpersuasive.
Note that the prior art is presumed enabled (see MPEP §2121(I)).
The MPEP provides that:
“A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)… Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971),”
(see MPEP section 2123(I-II)).
Moreover, Applicant ignores the teachings of Kiovig which clearly point to and teach successful use of a concentration of 20ppm of polysorbate 80. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant next argues that the present Application shows criticality of the concentration of non-ionic detergent at a concentration of 20ppm. After reviewing the full disclosure, it appears that the claimed range of non-ionic detergent concertation is better, but not so much better as to be critical. The disclosure shows that compositions having 20ppm non-ionic detergent (F4 and F5) have fewer subvisible particles as a measure of stability (see table 5) as compared to formulations having 0-10ppm (see F1-3) or 30ppm (see F6 and F7) non-ionic detergent (polysorbate 80 or Pluronic F68). However, the comparison of 20ppm non-ionic detergent to below 10 or 30ppm non-ionic detergent never consistently appears to be a significant improvement. Even in Table 5, where the greatest improvement of a 20ppm formulation is shown (F5), F4 does not appear to be significantly improved or different than the other formulation having non-ionic detergent present at concentrations outside of the claimed range of 15-25ppm. Therefore, the presently described improvement appears to be more reminiscent of routine optimization resulting from adjusting concentrations of detergent disclosed in the art, here, with adjusting the concentration within the range of concentrations taught by Huille. Huille teaches concentration ranges which encompass the claimed concentration ranges and therefore makes obvious the claimed concentrations/ranges for the reasons set forth in the rejections of the claims under 35 USC 103.
Applicant alleges that Huille teaches away from a composition having 40ppm surfactant or less. The sections Applicant cites from Huille merely relate to Huille’s preferred embodiments. That Huille preferred embodiments having more than 40ppm surfactant is insufficient to establish that Huille taught away from concentrations of 40ppm surfactant or less in a way that would discourage or discredit one of ordinary skill in the art from pursuing a formulation having less than 40ppm of surfactant. A true “teaching away" from a concept must be explicit, not just an otherwise general suggestion. Furthermore, “the prior art' s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Applicant points to the following data points to support their assertion of criticality/surprising results: Tables 1-5 and Tables 11-12. First, Applicant asserts a person of ordinary skill in the art (POSITA) would have expected a linear relationship between increasing concentrations of polysorbate 80 and markers indicating increased stability. Applicant is reminded that unexpected results must be sufficient to “ascertain a trend in the exemplified data that would allow [them] to reasonably extend the probative value thereof” (in re Clemens; citation in MPEP section 2145). The Examiner is not persuaded that the evidence supports the Applicant’s assertion of a surprising result/criticality or that the evidence in the disclosure is commensurate with the scope of the claimed range of non-ionic detergent and, therefore, the scope of the claims. Applicant has the burden of explaining why results are surprising (see MPEP section 716.02(b)). Second, even if, in arguendo (hypothetically for the sake for argument, not to be taken as an admission of correctness), a linear relationship would have been expected by a POSITA, Applicant fails to show that 20ppm polysorbate 80 is critically and unexpectedly better than 10ppm and 30ppm poloxamer/polysorbate 80 because Applicant fails to show that the 20ppm polysorbate 80, is more stable than 10ppm or 30ppm formulations across the measured markers of stability. There is no apparent statistically significant difference between F1 (335), F2 (340), F4 (336), and F6 (338) or between F1 (335), F3 (342), F5 (346), and F7 (348) regarding osmolality (see Table 1). There is no apparent statistically significant difference between F1 (0.122), F2 (0.085), F4 (0.067), and F6 (0.066) or between F1 (0.122), F3 (0.043), F5 (0.042), and F7 (0.043) regarding turbidity (see Table 2). There is no apparent statistically significant difference between F1 (65.1), F2 (54.2), F4 (67.9), and F6 (67.9) regarding monomer intensity (see Table 3). Thus, there is no support that any non-ionic detergent would be critical at this 20ppm concentration. Therefore, the claims as drafted fail to be commensurate with, and therefore made non-obvious in light of, the data presented. Further, there is no support that any unsurprising result would be seen at concentrations above or below 20ppm (ex: 18ppm or 22ppm). Therefore, the claims as drafted fail to be commensurate with, and therefore made non-obvious in light of, the data presented. Moreover, this difference is not observed at Time 0, after 2 hours, or after 4 hours. This difference in monomer intensity only appears after 6 hours, indicating that any asserted criticality/surprising result is highly time sensitive (unpredictable), occurring only after 6 hours and potentially not enduring beyond the 6 hour time point(unpredictable). Therefore, the claims as drafted fail to be commensurate with, and therefore made non-obvious in light of, the data presented in table 3. There is no apparent statistically significant difference between F1 (46), F2 (42.22), F4 (43.97), and F6 (43.97) or between F1 (46), F3 (44.03), F5 (38.21), and F7 (42.50) regarding total intensity at 90 degrees (see Table 4). Thus, there is no support that any non-ionic detergent would be critical at this 20ppm concentration (or even that polysorbate is critical at this concentration). Therefore, the claims as drafted continue to fail to be commensurate with the data presented such that allegedly surprising results are insufficient to overcome the rejections under 35 USC §103. Further, there is no support that any unsurprising result would be seen at concentrations above or below 20ppm (ex: 18ppm or 22ppm). Therefore, the claims as drafted fail to be commensurate with, and therefore made non-obvious in light of, the data presented. There is however, an apparent statistically significant difference between F1 (39980/2999), F2 (3221/93), F4 (8043/1322), and F6 (15908/3496) regarding subvisible particles (see Table 5). This improvement at or below 20ppm is only present after 4hrs, where prior to the 4hr mark, the data suggest that a concentration of greater than 20ppm non-ionic surfactant confers greater stability. This indicates that the improvement is unpredictably time-dependent and raises the question of how predictable and durable any observed benefit/stability may be. Moreover, the claimed formulation is incommensurate in scope with the formula of F4. Thus, there is no support that any non-ionic detergent would be critical at this 20ppm concentration. Therefore, the claims as drafted fail to be commensurate with, and therefore made non-obvious in light of, the data presented. Moreover, this difference is not observed at all time points and is not clearly consistent among particles between 10+ and those greater than or equal to 25 micrometers. This inconsistency indicates that any asserted criticality/surprising result is time sensitive and sensitive to the size of the subdivisible particles examined (unpredictable). Therefore, the claims as drafted fail to be commensurate with, and therefore made non-obvious in light of, the data presented in table 5 due to the lack of consistency and unpredictability of the data across conditions. Note that because tables 11-14 do not provide comparisons of the 20ppm formulations with the 10ppm and 30ppm formulations and therefore are unable to show any criticality/surprising results for the claimed formulations comprising 20ppm polysorbate 80, 215mM glycine, pH 4.8, and osmolality 336.
Applicant attempts to bolster these old arguments by alleging misinterpretation. Huille (English translation) states that “Preferably, the surfactant is added to steps b) and / or
d)..” (see page 6/16) and further adds that for step d, The concentration of nonionic detergent sufficient to stabilize the composition according to the invention is preferably between 0 and 1000ppm, preferably between 0 and 300 ppm, preferably between 0 and 50 ppm (see page 5/16-6/16). Grammatically, this clearly teaches a step where detergent is only added at step d and where the amount added may be 0-50ppm which encompasses the narrower range of 0-40ppm. The MPEP provides that:
“A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)… Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971),”
(see MPEP section 2123(I-II)). Applicant’s own interpretations are noted, but are insufficient to surmount what is taught by the clear text of the Huille reference. Where Huille teaches that 0-50ppm detergent may be added in step D, there is the option and teaching to add 1-50 ppm, which is more than no detergent (stated in response to Applicant’s argument that Huille somehow teaches away by teaching that some amount of detergent is needed for better stabilization). Therefore, these arguments are unpersuasive and the rejections of record for obviousness are maintained.
C. Applicant argues that the cited references do not make obvious 215 mM of glycine.
Response: As discussed above, the composition of Huille further comprises glycine at a concentration of 200-300mM (see claim 3 of Huille). To arrive at 215 mM from the range of 200-300mM is an obvious matter of routine optimization. This argument is unpersuasive.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Shi, S. (Overcoming Formulation Challenges for Biopharmaceutical Development, Cambridge Healthtech Institute, CHI’s 7th Annual The Bioprocessing Summit, August 3-4, 2015, retrieved from: https://www.bioprocessingsummit.com/formulation-challenges/15) teaches that
“PS20 and PS80 are compatible with m-cresol (at 2.8 mg/mL) when their levels were not greater than 20 ppm. Significant losses of polysorbates were observed when PS20 and PS80 concentrations were above 50 ppm… the agitation study demonstrated that even trace levels of PS20 and PS80 (e.g., 20 ppm) could stabilize the protein against fibrillation and aggregation.”
US 9463241 B2 is deemed relevant to the low concentration (20ppm or less) of nonionic surfactant for stabilizing an IgG antibody at a lower concentration than instantly claimed.
US 20150110799 A1 is deemed relevant to the claimed concentration of nonionic detergent (see paragraph 0556).
US 20160039924 A1 is deemed relevant to the concentration of nonionic detergent (see paragraph 211).
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
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678