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
Claims 1-5, 7, 9-12, 14-15, 17, 20, 23, 25, 27, 29, 32-33, 35, 37-38, 40-41 are currently pending and are subject to this Office Action.
Information Disclosure Statement
The references cited on the information disclosure statement(s) were considered and have been made of record.
Claim Interpretation
As set forth in the prior Office Action, claim 1 states “formulation is free of amino acids selected from arginine, lysine, and proline…”. Based on the broadest reasonable interpretation of the claims, claim 1 merely requires that the formulation excludes at least one of the amino acids listed.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Claim Rejections
In view of the Applicant’s claim amendments: the previous rejections under 35 U.S.C. 112(b) and 35 U.S.C. 102 are hereby withdrawn.
Claim Objections
Claims 9-12 and 14 are objected to for depending on a rejected base claim.
Appropriate correction is required.
Maintained 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.
Claims 1-5, 7, 9-12, 14-15, 17, 20, 23, 25, 27, 29, 32-33, 35, 37-38, 40-41 are/stand rejected under 35 U.S.C. 103 as being anticipated by Park1 in view of Kashi2 and Lee3.
Park discloses an aqueous solution formulation: comprising the Fc fusion protein, etanercept, which comprises a heterologous ligand-binding polypeptide fused to an Fc portion of an immunoglobulin, IgG1 at 25 mg/ml (see Examples 1-4, [0046] in particular, where “‘TNFR:Fc formulation’ means a formulation containing etanercept protein”; claim 8 and [002]- “a fusion protein (TNFR:Fc; etanercept) prepared by fusing the extracellular ligand-binding portion of human p75 human tumor necrosis factor receptor to the Fc domain of human IgG1 has been used as an agent for treating rheumatoid arthritis” reads on instant claims 1(i), 2-4, and 7, as well as the amendment to claim 5); and comprising ammonium sulfate at a concentration of 5-200 mM to stabilize the Fc fusion protein (see Examples 1-4, in particular: [0059]- “A stabilization buffer composition containing no excipient for aggregation inhibition (negative control formulation), a formulation containing 25 mM arginine (positive control formulation), a formulation containing 50 mM ammonium chloride, a formulation containing 25 mM ammonium sulfate [respectively]… were used. Each of the formulations was stored at…”; Tables 1-2 and Fig. 4-5; and claim 7- “wherein the ammonium salt is comprised at a concentration of 5-500 mM”; where ammonium sulfate is a source for sulfate ions, as disclosed in the instant specification, see p. 5 par. 5; reads on instant claims 1(ii) and 5); and wherein the formulation is free of amino acids and magnesium ions (see Examples 1-4, in particular: [0050]- “The experiment was performed to compare the degree of aggregation between the use of the excipient arginine that is used to inhibit the aggregation of TNFR:Fc, and the use of other excipients”; [0053]- “the experiment was performed to prove the aggregation inhibitory effect of ammonium sulfate as another ammonium salt and a combination of other excipients generally known to have the ability to inhibit protein aggregation. Specifically, each excipient was added to a stabilization buffer containing 25 mg/ml TNFR:Fc. 1% w/v sucrose, 100 mM sodium chloride and 25 mM sodium phosphate (pH 6.4), and then each buffer was stored...”; Tables 1-2 and Fig. 4-5; reads on “free of amino acids selected from” in instant claim 1, as well as claims 7, 32, and amendment to claim 17).
Park further discloses the ammonium sulfate formulation further comprising: the inorganic multivalent anion, phosphate; the uncharged tonicity modifier, sucrose; and the charged tonicity modifier, sodium chloride, wherein the formulation is a pH of 6.4, and wherein the buffer, sodium phosphate, is present at a concentration of 25 mM (see Example 3, in particular [0053]- “the experiment was performed to prove the aggregation inhibitory effect of ammonium sulfate as another ammonium salt and a combination of other excipients generally known to have the ability to inhibit protein aggregation. Specifically, each excipient was added to a stabilization buffer containing 25 mg/ml TNFR:Fc, 1% w/v sucrose, 100 mM sodium chloride and 25 mM sodium phosphate (pH 6.4), and then each buffer was stored”; claim 4; reads on claims 8, 17, amendment to claim 20, 23, and 25).
Park further discloses: the ammonium sulfate formulation further comprising the inorganic multivalent anion, phosphate (see [0053]) and that ammonium sulfate inhibits protein aggregation similar to ammonium chloride (see Example 4, in particular [0057]- “the formulations containing the ammonium salt effectively inhibited the aggregation of the protein, and ammonium sulfate also inhibited the aggregation of the protein, similar to ammonium chloride”; Fig. 4-5); combining ammonium salt, in particular ammonium chloride, with succinate at a concentration of 5-200 mM in formulation (see claims 2 to 3- “further comprising succinate… at a concentration of 5-200 mM”; [001], [009]- “a composition containing an ammonium salt or a combination of an ammonium salt and succinate can increase the stability of a fusion protein of a protein and an Fc domain by inhibiting the aggregation of the fusion protein so that it can be easily stored for a long period of time”; [0035]-[0037]); aggregation in the formulation containing sodium succinate as a buffer was significantly lower than that in the formulations containing other buffers (see Example 4, in particular [0063]- “aggregation in the formulation containing sodium succinate as a buffer was significantly lower than that in the formulations containing other buffers at pH 6.5”; Example 5, in particular [0060] to [0062]- “in order to maximize the effect of the ammonium chloride excipient proven to have the effect of inhibiting the aggregation of the fusion protein, formulation solutions prepared using various kinds of buffers… sodium phosphate, sodium succinate, sodium citrate and histidine buffers which are frequently used in protein formulations. 50 mg/ml TNFR:Fc was stored in 100 mM sodium chloride, 50 mM ammonium chloride and 25 mM of each of the above-described four buffers… it was shown that aggregation in the formulation containing sodium succinate as a buffer was significantly lower than that in the formulations containing other buffers”; Fig. 6; reads on instant claims 9 and 14).
Park further discloses an etanercept formulation comprising ammonium chloride and the non-ionic surfactant, polysorbate 20 at 0.1% w/v (see [0054]- “a formulation containing 50 mM ammonium chloride and 0.1% w/v polysorbate 20”; where 0.1% w/v polysorbate 20 = 0.1 g/ 100 mL = 1000 ug/mL; reads on instant claim 27).
Park discloses a composition for treating arthritis, which comprises an ammonium salt and a fusion protein, wherein the ammonium salt is ammonium sulfate (see claims 23 and 28; reads on “pharmaceutical formulation” in instant claim 35).
Park discloses a method of stabilizing a protein-Fc domain in an aqueous solution by adding ammonium sulfate at a concentration of 5-500 mM (see [0033]- “The present inventors have found that, when a fusion protein of a protein and an Fc domain is stored in an aqueous solution containing an ammonium salt, the aggregation of the fusion protein is effectively inhibited. Thus, the present invention provides a composition for stabilizing a fusion protein of a protein and an Fc domain, the composition containing an ammonium salt”, where “inhibiting aggregation” reads on “inhibiting formation of high molecular weight species” in instant claim 41, as defined by the instant specification p. 10 last par.; claims 12 and 17-18; reads on amended claims 40-41).
The prior art of Park differs from the instantly claimed invention as follows: Park does not expressly disclose combining sulfate ions with maleate and copper ions in the formulation for etanercept, or the incorporation of preservatives.
Kashi discloses: aqueous formulations for etanercept that improve stability (see [0005]- “The biopharmaceutical protein etanercept (TNFR:Fc) is a Fc-fusion protein which is known to be susceptible to misfolding, fragmentation and aggregation. Therefore, there is a need for stabilizing liquid (aqueous) formulations capable of mitigating these issues when a pharmaceutical composition comprising etanercept is stored or marketed as a liquid product”); citrate and maleate were found to be the optimal buffers for etanercept formulation (see Example 3, in particular [0160]- “The biochemical stability data indicated that the optimal buffers were Citrate, Citrate Phosphate and Maleate”); formulations comprising 25 mM of citrate and 25 mM of maleate (see [0151]- “Citrate buffer was prepared by first preparing stock solutions of 25 mM citric acid and 25 mM sodium citrate. The citric acid solution was titrated into the sodium citrate solution until the desired pH was reached”; [0154]- “Maleate buffer was prepared by making a 25 mM solution of maleic anhydride and adjusting to the desired pH with 1N NaOH”; reads on “citrate and maleate” in claim 1, as well as claims 10-12 and 33).
Kashi further discloses: a pharmaceutical formulation of etanercept suitable for subcutaneous, intramuscular, intravenous, or pre-filled syringe injection/infusion (see [0139] to [0140]- “A pharmaceutical formulation comprising etanercept in one of the formulations of this invention is particularly useful for parenteral administration, i.e., subcutaneously, intramuscularly, intravenously, intraperitoneal, intracerebrospinal, intra-articular, intrasynovial, and/or intrathecal. Parenteral administration can be by bolus injection or continuous infusion. Pharmaceutical compositions for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. A formulation of the invention can be administered, for example, with medical devices known in the art, such as pre-filled syringes and autoinjectors”; reads on instant claims 15 and 37-38); using salts or other tonicity agents to achieve an isotonic formulation suitable for human or animal administration (see [0133]- “Salts may be used in accordance with embodiments of the invention to, for example, adjust the ionic strength and/or the isotonicity of a formulation and/or to improve the physical stability of a protein or other ingredient(s) of a composition”; [0135]- “Tonicity agents and/or stabilizers included in a liquid formulation can be used, for example, to achieve a physiologic osmolality (e.g., isotonicity), of a formulation that is suitable for human or animal administration”; reads on instant claim 15);
Lee discloses a pharmaceutical formulation for etanercept further comprising preservatives, including those listed in instant claim 29 (see [0047]- “The liquid formulation according to the present invention may further comprise a preservative. The preservative refers to a chemical that is added to pharmaceutical formulations as an antimicrobial agent. Examples of the preservative may include benzalkonium chloride, benzethonium, chlorhexidine, phenol, m-cresol, benzyl alcohol, methylparaben, propylparaben, chlorobutanol, o-cresol, p-cresol, chloro-cresol, phenylmercuric nitrate, thimerosal, benzoic acid, etc., but are not limited thereto. These preservatives may be used either alone or in combinations of two or more thereof”; reads on claim 29).
Obviousness Analysis: Regarding the incorporation of the amendment to claim 1(iii), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Park to incorporate the teachings of Kashi by adding citrate and maleate, as they were found to be the optimal buffers for etanercept per the teachings of Kashi. See MPEP 2143(I)(G). Furthermore, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. Thus, the idea of combining sulfate, maleate, and citrate ions in formulation flows logically from their having been individually taught in the prior art to improve stability of fusion proteins, in particular etanercept. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding claims 9 and 14, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have specifically combined ammonium sulfate with the organic multivalent anion, succinate, instead of phosphate. One would have been motivated to use succinate instead of phosphate, as it was shown to be more effective in inhibiting protein aggregation. See MPEP 2143(I)(B), (G).
Regarding claims 15 and 37-38, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Park to incorporate the teachings of Kashi by developing pharmaceutical formulation of etanercept, wherein the formulation is isotonic and suitable for subcutaneous, intramuscular, intravenous, or pre-filled syringe injection/infusion, as doing so amounts to no more than combining prior art elements according to known methods to yield predictable results. See MPEP 2143(I)(A).
Regarding claim 27, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have specifically combined ammonium sulfate rather than ammonium chloride with the non-ionic surfactant, polysorbate 20, in formulation, as doing so amounts to no more than combining prior art elements according to known methods to yield predictable results. See MPEP 2143(I)(A).
Regarding claim 29, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to developed the pharmaceutical formulation of etanercept, wherein the formulation further comprises a preservative, as doing so amounts to no more than combining prior art elements according to known methods to yield predictable results. See MPEP 2143(I)(A).
Additionally, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art of protein formulation to simply make compositions for optimal protein functioning, e.g., stability. In other words, the formulation, e.g., as set forth in instant claim 1, is a result-effective variable, where the optimum formulation can be determined via routine optimization. See MPEP 2144.05(II). Thus, a skilled artisan could predictably and reasonably arrive at the present invention in view of the prior art, as discussed above.
Accordingly, claims 1-5, 7, 9-12, 14-15, 17, 20, 23, 25, 27, 29, 32-33, 35, 37-38, 40-41 are rejected.
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.
Copending Application No. 17/634,120
Claims 1-5, 7, 9-12, 14-15, 17, 20, 23, 25, 27, 29, 32-33, 35, 37-38, 40-41 are/stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-7, 9-11, 17-30, and 34 of copending Application No. 17/634,120 (reference application) in view of Park (supra), Kashi (supra) and Maloney4.
This is a provisional nonstatutory double patenting rejection.
MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analyses.
The disclosures of Park are discussed above and are incorporated herein.
Obviousness analysis: Regarding claims 1-4, 7, 9-12, 14, 17, 23, 25, and 32, the reference application: an aqueous solution composition of pH in the range of 4.0-8.5 comprising: an engineered protein construct comprising an Fc domain, wherein the protein is etanercept, abatacept, or belatacept and wherein the present at a concentration of 1-400 mg/ml; optionally one or more buffers, including citrate and maleate, at a concentration of 05- mM; optionally one or more neutral amino acids; and an uncharged tonicity modifier; wherein the buffers are present in the composition at a total concentration of 0-5 mM (see claims 1-3, 7, 21, 25).
Regarding claims 18, 27, 29, and 35, the reference application claims: An aqueous solution composition according to claim 1 comprising an uncharged tonicity modifier selected from polyol, glycerol, 1,2-propanediol, mannitol, sorbitol, sucrose, trehalose, PEG300 and PEG400, wherein the concentration of the uncharged tonicity modifier is 50-1000 mM (see claims 9-11; reads on instant claim 18); An aqueous solution composition according to claim 1 comprising a non-ionic surfactant at a concentration of 10-2000 ug/ml (see claims 26-29; reads on instant claim 27); An aqueous solution composition according to claim 1 comprising a preservative selected from the group consisting of phenol, m- cresol, chlorocresol, benzyl alcohol, propyl paraben and methyl paraben (see claim 30; reads on instant claim 29); An aqueous solution composition according to claim 1 which is a pharmaceutical composition (see claim 34; reads on instant claim 35).
Maloney discloses: arginine-free formulations have several benefits relative to arginine-stabilized solutions, including reduced cost and a reduced incidence of side-effects associated with the presence of arginine, while still maintaining efficacy in stabilizing the protein in formulation (see “Summary of Invention” on p. 1).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art to have modified the aqueous solution, as claimed by the reference application, by adding ammonium sulfate at the concentration specified by Park, to arrive at the present invention, as the prior art of Park suggests ammonium sulfate effectively inhibits aggregation of fusion proteins in formulation (see [0033] and Example 4, in particular [0057]). It would have been prima facie obvious to have excluded the amino acids set forth in instant claim 1, arginine in particular, as the prior art of Maloney discloses that arginine-free formulations have several benefits relative to arginine-stabilized solutions, including reduced cost and a reduced incidence of side-effects associated with the presence of arginine, while still maintaining efficacy in stabilizing the protein in formulation.
Regarding claims 5, 13, 20-21, and 40-41, the reference application does not claim the elements required. As set forth in the 35 U.S.C. 102 and 103 rejections above, Park remedies these deficiencies. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated the disclosures of Park, as doing so amounts to no more than combining prior art elements according to known methods to yield predictable results (see MPEP § 2143).
Regarding claims 15, 33, and 37-38, the reference application does not claim the elements required. As set forth in the 35 U.S.C. 103 rejections above, Kashi remedies these deficiencies. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated the disclosures of Kashi, as doing so amounts to no more than combining prior art elements according to known methods to yield predictable results (see MPEP § 2143).
Copending Application No. 18/546,578
Claims 1-5, 7, 9-12, 14-15, 17, 20, 23, 25, 27, 29, 32-33, 35, 37-38, 40-41 are/stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-8, 10-11, 19-25, 27-29, 31, 33, 36-37, 39, 41, 45 of copending Application No. 18/546,578 in view of Park (supra), Kashi (supra), and Maloney (supra), for the same reasons as discussed in the provisional nonstatutory double patenting rejection above (see Application 17/634,120).
This is a provisional nonstatutory double patenting rejection.
The disclosures of Application 17/634,120, Park, Kashi, and Maloney are discussed above and are incorporated herein.
Response to Arguments
Applicant's arguments filed 19 May 2025 have been fully considered but they are not persuasive. Applicable arguments pertaining to maintained rejections are addressed below.
In view of the Applicant’s claim amendments, the previous rejections of the claims under 35 U.S.C. 112(b) and 35 U.S.C. 102 are rendered moot.
The previous claim rejections under 35 U.S.C. 103 and NSDP are maintained, and revised in view of the Applicant’s claim amendments, as set forth above.
In response to Applicant’s argument that “there must be a reason (or motivation) that would have prompted a person having ordinary skill in the art to select and combine those elements from the specific teachings in the prior art in the claimed manner”: it is the Examiner's understanding that Applicant is attempting to rebut a determination of obviousness based upon the difference statements set forth in the rejections under 35 USC § 103. This is not persuasive because, as noted at MPEP § 2141.02, ascertaining the differences between the prior art and the claims at issue is part of the formation of a proper rejection under 35 USC § 103 (see also MPEP § 2141(II), discussing the basic factual inquiries of an obviousness determination). Accordingly, any argument premised upon the identification of differences set forth by the Examiner are insufficient to establish non-obviousness absent evidence addressing the remainder of the rejection. Here, the claimed invention has been identified as obvious for multiple exemplary rationales, including MPEP § 2143(I)(A); MPEP § 2143(I)(B); MPEP § 2143(I)(G), and In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (see above). In the absence of evidence that the elements of such rationales were not fully satisfied, a prima facie case of obviousness has presumably been established based upon at least one or more of such rationales.
In response to Applicant’s argument that “There is no teaching in Park that the disclosed formulations should include sulfate ions”, Park teaches the formulation comprising ammonium sulfate, which is defined by the instant specification as a source of sulfate ions.
In response to Applicant’s argument that “Kashi discloses that citrate, maleate, and citrate phosphate buffers are optimal buffers, but that TRIS-maleate is a sub-optimal buffer”, it is the Examiner’s understanding that Applicant is alleging that the individual references address additional facts and scientific issues that are not all relevant to the instant invention, and were not relied upon by the Examiner. The relevance of the additional teachings is not unambiguously explained by the Applicant. It is neither disputed nor dispositive of obviousness that the prior art references inform artisans of additional information. However, the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and here the additional information does not detract or erase the disclosures, particularly Kashi’s teaching that citrate and maleate are optimal buffers, relied upon by the Examiner in the rejection of record. Also, it is noted that preferred embodiments do not constitute a teaching away from nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ
423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)
In response to Applicant’s argument that “had no reason to consider Park in view of Kashi,” if Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability.
Furthermore, in response to applicant's arguments against the references individually, particularly when stating “Lee does not cure the deficiencies of Park in view of Kashi”, 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).
Moreover, it is the Examiner’s understanding that Applicant alleges “A person skilled in the art considering Park would not have had reason to modify the compositions of Park”. Presumably, the Applicant is alleging that one of ordinary skill in the protein formulation arts (a) could not use modern search engines to find relevant prior art, (b) would otherwise be unaware of the prior art, or (c) just dismiss the existence of the reference. This is not persuasive because, per MPEP § 2141.03, “The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time” (see, e.g., MPEP § 2141.03(I)). Here, the Applicant does not dispute that all references constitute “prior art”. Furthermore, the Applicant does not dispute that prior art pertaining to etanercept formulation is “relevant art”, Therefore, the reference constitutes “relevant art” available “at the relevant time”. Accordingly, any arguments suggesting that a reasonable artisan in the arts would be unaware of the reference or otherwise just dismiss the reference is not persuasive, because such arguments amount to an attempt to simply dismiss the existence of the prior art teachings for etanercept formulation set forth in Kashi and Lee. Rather, the reference is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)).
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEA S O'BRIEN whose telephone number is (703)756-4793. The examiner can normally be reached Monday - Friday 5:00AM - 2:30PM PT.
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/LEA S O'BRIEN/Examiner, Art Unit 1646
/MARK HALVORSON/Primary Examiner, Art Unit 1646
1 US20150313996; art of record.
2 US20150290325; art of record.
3 US20170028020; art of record.
4 WO2013006454; art of record.
Prosecution Insights