DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 3/20/26 in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/20/26 has been entered.
Claims 12, 15, 17, 20-21, 35-36 are pending and are under examination.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 12, 15, 17, 20-21, and 35-36 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Adler (U.S. 20110076273) in view of Goldenberg et al. (WO 2010/011697 A1), and U.S. 2006/0088523 (Andya et al).
Adler teaches a highly concentrated, stable liquid pharmaceutical formulation of an anti-CD20 antibody at concentrations of about 20 to about 350mg/ml, about 1 to about 100 mM of a buffering agent at a pH of 5.5, about 1 to 500 mM of a stabilizer, or a mixture of two stabilizers, from 0.01 to 0.1% of a surfactant, and preferably a hyaluronidase enzyme (see page 2). Adler teaches that the hyaluronidase enzyme is optional, and that the antibody can be formulated without the hyaluronidase, i.e. they teach a composition “consisting of” the antibody, a buffer, one or two stabilizers, and surfactant, see page 12, paragraph 132, in particular). Adler teaches that a preferred anti-CD20 antibody concentration is 150 mg/ml (i.e. “about” 160 mg/ml, see paragraph 115). Adler teaches that a preferred buffering agent is histidine buffer, preferably 30mM (see paragraph 116, in particular). Adler teaches that the first stabilizer can be a saccharide, at a concentration of 210 mM, and the second stabilizer is preferably methionine (i.e. an amino acid, see paragraph 118, in particular). Adler teach that the surfactant is preferably polysorbate 20, at a concentration of 0.02% (see paragraph 119). A concentration of 0.02%, as taught by Adler, corresponds to 0.2 mg/ml. Adler teaches sorbitol as a type of saccharide for use in the disclosed compositions (see paragraph 101, in particular).
Adler differs from the claimed invention in that it does not explicitly teach veltuzumab as the anti-CD20 antibody.
Goldenberg et al. teaches the antibody veltuzumab and its wondrous and amazing properties (see Example 14 and [0049]).
The ‘689 patent formulations of antibodies, including veltuzumab, wherein the antibodies can be formulated by the addition of a stabilizing agents such as mannitol and polysorbate, which protect antibodies against aggregation (see paragraph 126, 172, Table 3, and claim 24, in particular). For example, see Table 3 of the ‘689 patent which exemplifies a high concentration liquid formulation of veltuzumab at a concentration of 162 mg/ml (i.e. “about” 160 mg/ml), and containing polysorbate and mannitol at a pH of 5.2. The ‘689 patent teaches adding polysorbate after antibody concentration.
Andya et al. teach a method of making a pharmaceutical formulation of an antibody, such as veltuzumab (hA20, see [0365]) at a concentration of about 100 to 200 mg/ml, in a liquid formulation with an amino acid (see [0372] ). The amino acid (such as histidine) can be at a concentration of about 10 to about 40 mM, and have a pH of about 5.5 (see page 5 and 32-33). The formulation can comprise a surfactant such as polysorbate 20 (see [0376]) and a saccharide such sorbitol or mannitol (see [0102], [0375]). Andya also teaches the use of a saccharide such as sorbitol or mannitol to reduce aggregate formulation, and that exemplary concentrations can range from about from about 60 mM to 250 mM. Andya teaches that said formulations are advantageous since they retard degradation of the antibody (see page 5 in particular). Andya teaches adding polysorbate can reduce insoluble aggregate formation, such as occurs upon shaking, and teaches a concentration of from 0.01% to about 0.1% (i.e. 0.1 mg/ml to 1 mg/ml, see claims and paragraph 376). Andya exemplifies a polysorbate concentration of 0.02%, i.e. 0.2 mg/ml, see examples.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use veltuzumab, as taught by Goldenberg, Andya, and the ‘689 patent, as the anti-CD20 antibody in the formulations of Adler. The ordinary artisan would be motivated to do so because Goldenberg et al. teaches the antibody veltuzumab and its wondrous and amazing properties (see Example 14 and [0049]). The ordinary artisan would have a reasonable expectation of success, since Andya and the ‘689 patent teach that it is a CD20 antibody that can be formulated with a buffer, sorbitol/mannitol, and polysorbate. Regarding the concentration of sorbitol, 40g/ml is equivalent to 220mM of sorbitol, given it’s molecular weight. Given that Adler teaches concentrations of 210 mM and Andya teaches up to 250mM, arriving at the claimed concentration of 40mg/ml (i.e. 220 mM) would be obvious.
Applicant’s arguments filed 3/20/26 have been fully considered, but they are not persuasive.
Applicant argues that the instant claims are not obvious since the specification discloses that the formulations provide unexpected results shown in Table 4, wherein a formulation with the recited amounts of polysorbate is critical in maintaining stability. The specification test polysorbate 20 at concentrations of 0.1, 0.2, and 0.3 mg/ml, and discloses that a 0.1 mg/ml concentration is sufficient to prevent particle formation after freeze-thaw, but that after shaking, 0.1 mg/ml reduces particle formation, but is not sufficient to completely avoid sub-visible particles (particles were 37000 with no polysorbate after shaking, with reduction to 2500 with 0.1 mg/ml of polysorbate 20, and further reduction to 97 or 77, with 0.2 or 0.3 mg/ml of polysorbate 20, respectively).
This is not persuasive of unexpected results for several reasons.
Unexpected results requires a comparison of the claimed invention to the closest prior art, and Applicants have the burden of explaining proffered data, see MPEP 716.02 (b) and (e).
In the instant case, the closest prior art is Adler, however, Applicant has not explained how the data in Table 4 represent an unexpected result compared with Adler. Applicant asserts that the unexpected result occurs as a result of including 0.2 mg/ml of polysorbate, however, the compositions of Adler are taught to preferably have a concentration of 0.02% of surfactant such as polysorbate 20, which corresponds to a 0.2mg/ml concentration.
Furthermore, unexpected results must be commensurate in scope with the instant claims. The asserted unexpected results in Table 4 are with 160 mg/ml Veltuzumab, 40 mg/ml sorbitol, and polysorbate 20, while the present claims encompass any “antigen binding fragment thereof”, any polysorbate surfactant, and sorbitol or mannitol at any concentration.
Furthermore, the reduction in aggregation/particle formation is an expected beneficial result of including a surfactant like polysorbate. The instant specification on page 53 teaches that “as expected” the addition of polysorbate 20 influences formation of particles. The fact that there is a lower limit is not unexpected.
Adler teaches that polysorbate functions to reduce aggregation (i.e. formation of particles, see paragraph 105). See also paragraph 107 and pages 25-26, wherein Adler teach that the formulations are stable and free of particles. Likewise, the ‘689 patent teaches that polysorbate serves to decrease protein aggregation (See column 3). See also Andya which teaches adding polysorbate can reduce insoluble aggregate formation, such as occurs upon shaking, and teaches a most preferred concentration of 0.02%, i.e. 0.2 mg/ml, see claims and paragraph 376). Thus, reducing aggregation or particle formation by including polysorbate is an expected result already taught in the prior art.
Applicant further argues that the results of Table 4 demonstrate criticality of the claimed range.
However, the only concentration tested outside the claimed range was 0.1 mg/ml, which reduced particles after shaking, but to a lesser degree than a 0.2 mg/ml or 0.3 mg/ml concentration of polysorbate 20.
See MPEP 716.02 (d), to establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). The single tested concentration of 0.1 mg/ml merely serves to demonstrate that there is a lower limit on the concentration of polysorbate that might be completely effective, which is not unexpected and does not establish criticality as compared to the range of the prior art.
Applicant further argues that polysorbate was not recognized as a results effective variable, and optimization is therefore not obvious.
As noted above, the prior art recognized surfactants such as polysorbate as results effective variable for reducing aggregation and particle formation.
Applicant argues that the claimed invention satisfies a long felt need.
Establishing long-felt need requires objective evidence that an art recognized problem existed in the art for a long period of time without solution. The relevance of long-felt need and the failure of others to the issue of obviousness depends on several factors.
Second, the long-felt need must not have been satisfied by another before the invention by the inventor. Newell Companies v. Kenney Mfg. Co., 864 F.2d 757, 768, 9 USPQ2d 1417, 1426 (Fed. Cir. 1988).
Long-felt need is analyzed as of the date the problem is identified and articulated, and there is evidence of efforts to solve that problem, not as of the date of the most pertinent prior art references. Texas Instruments Inc. v. Int’l Trade Comm’n, 988 F.2d 1165, 1179, 26 USPQ2d 1018, 1029 (Fed. Cir. 1993).. See MPEP 716.04.
See also MPEP 716.01 (c), objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Examples of statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor.
Applicant asserts that obtaining highly concentrated liquid formulations of antibodies was a problem in the field and heretofore, no adequate solution has been found. However, Adler teaches highly concentrated liquid formulations of anti-CD20 antibodies. Andya also teaches pharmaceutical formulation of an antibody, such as veltuzumab (hA20, see [0365]) at a concentration of about 100 to 200 mg/ml, in a liquid formulation (i.e. high concentration). Applicant provides no evidence and only attorney argument.
Claims 12, 15, 17, 20-21, and 36 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over U.S. Pat. 9,468,689 (of record) in view of Yang et al. (WO 2004/001007 A2) and U.S. 2006/0088523 (Andya et al., of record).
The ‘689 patent teaches in a liquid pharmaceutical formulation of veltuzumab ( see claims 1-2,8,24 and column 3, 13-14 and 40, in particular). A surfactant such as polysorbate can be added to the formulation (see claim 1,7, and column 41). The formulation can contain mannitol or sorbitol for stabilization (see claim 1 and column 31, in particular). The formulation can have a pH of 5.2 or about 5.2 (see claim 6 and abstract). The ‘689 patent teaches that formulations of antibodies, including veltuzumab, wherein the antibodies can be formulated by the addition of a stabilizing agents such as mannitol and polysorbate, which protect antibodies against aggregation (see paragraph 126, 172, Table 3, and claim 24, in particular). For example, see Table 3 of the ‘689 patent which exemplifies a high concentration liquid formulation of veltuzumab at a concentration of 162 mg/ml (i.e. “about” 160 mg/ml), and containing polysorbate and mannitol at a pH of 5.2. Thus, the ‘689 patent teaches a liquid formulation consisting of 162 mg/ml veltuzumab, a buffering agent, polysorbate surfactant and mannitol.
The disclosure of the ‘689 patent differs from the claimed invention in that it does not teach use of pH 5.5 histidine as the buffer, or the claimed concentrations of polysorbate.
Yang et al. discloses the use of diafiltration and ultrafiltration with a buffering agent consisting of histidine to obtain an anti CD20 antibody at a concentration from 50 to 250 mg/ml, such as 200 or 225 mg/ml in liquid formulation (see claims 22-41, pages 4-6,12,10-13,15,21 ). Yang et al. teaches use of histidine in the range of 2 to 48 mM and at a pH of 5.5 (see page 9-12). Yang et al. teach that histidine buffer is advantageous, since it lowers viscosity and reduces antibody aggregation relative to what is obtained using other buffers (see page 15, in particular).
Additionally, Andya et al. teach a method of making a pharmaceutical formulation of an antibody, such as veltuzumab (see [0365]) at a concentration of about up to 250 mg/ml, in a liquid formulation with an amino acid (see pages 5 and 33). The amino acid (such as histidine) can be at a concentration of about 10 to about 40 mM, and have a pH of about 5.5 (see page 5 and 32-33). The formulation can comprise a surfactant such as polysorbate 20 (see pages 5 and 33) and a saccharide such sorbitol or mannitol (see [0102], [0375]). Andya teaches that said formulations are advantageous since they retard degradation of the antibody (see page 5 in particular). Andya teaches adding polysorbate can reduce insoluble aggregate formation, such as occurs upon shaking, and teaches a concentration of from 0.01% to about 0.1% (i.e. 0.1 mg/ml to 1 mg/ml, see claims and paragraph 376). Andya exemplifies a polysorbate concentration of 0.02%, i.e. 0.2 mg/ml, see examples.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to substitute a buffer consisting of histidine at pH 5.5, as taught by Yang et al. and Andya, for the citrate buffer in the antibody formulations produced by ultrafiltration in the ‘689 patent. The ordinary artisan at the time the invention was made would have been motivated to do so and have a reasonable expectation of success, since they teach that histidine buffer is advantageous, since it lowers viscosity and reduces antibody aggregation relative to what is obtained using other buffers. Additionally, one of ordinary skill in the art would have been also been motivated to formulate the resulting antibody by dilution and addition of polysorbate 20, and sorbitol/mannitol as taught by Andya, since the reference teaches that formulating with polysorbate and sorbitol results in a formulation that retards degradation of the antibody. Regarding the specific concentrations of histidine, polysorbate and sorbitol/mannitol recited in the present claims, it is noted that they could be obtained with only routine optimization. “[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). Furthermore, Andya teaches adding polysorbate at a concentration of from 0.01% to about 0.1% (i.e. 0.1 mg/ml to 1 mg/ml, see claims). Thus, the concentration in the instant claims fall within the range of concentrations taught in the prior art to be suitable for use as stabilizing agents in antibody formulations, rendering the instant claims obvious. Andaya also teaches the use of a saccharide such as sorbitol or mannitol to reduce aggregate formulation, and that exemplary concentrations can range from about 10 mM to about 1 M, for example from about 60 mM to 250 mM. Given the molecular weight of sorbitol (182), the recited concentration of 40 mg/ml is equivalent to 220 mM. Thus, Andaya teaches concentrations overlapping with the concentration recited in the present clams, an in fact teaches a preferred embodiment of using 240 mM. This is very close to 40 mg/ml recited in the present claims. However, Andaya teaches that concentrations as low as 10 mM can be effective in reduce aggregation. See also the ‘689 patent which exemplifies a 12 mg/ml concentration of mannitol (see Table 3). Thus, optimizing the formulations to have a 40 mg/ml concentration to achieve reduced aggregation would be well within the purview of the ordinary artisan.
Applicant’s arguments filed 9/12/25 have been fully considered, but they are not persuasive.
Applicant argues that that the claims are not obvious for the reasons set forth above.
The claims stand rejected for the same reasons set forth above.
Claims 12, 15, 17, 20-21, and 36 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Yang et al. (WO 2004/001007 A2) in view of Goldenberg et al. (WO 2010/011697 A1), U.S. Pat. 9,468,689, and U.S. 2006/0088523 (Andya et al), all of record
Yang et al. discloses a method for producing a pharmaceutical composition comprising antibodies have the steps of: a) providing an initial antibody preparation in a histidine buffer, b) subjecting the antibody preparation to membrane filtration to produce an antibody preparation having a higher concentration of antibodies than the initial antibody preparation, and c) combining the concentration antibody preparation of step b) with one or more pharmaceutically acceptable carriers to produce a pharmaceutical composition (see claim 62 and page 7, in particular). Yang teaches preparing anti-CD20 antibodies (see page 14, in particular). Yang et al. teaches the use of histidine at ranges of pH and concentrations encompassed by those recited in the present claims (see pages 10-12, 12, histidine from 5 to about 40 mM, and pH range of 5.5-6). Yang et al. teach that therapeutic antibodies can be used at a variety of concentrations between 100-300 mg/ml (see page 2, penultimate paragraph) and that antibodies can be prepared at about 150 mg/ml or 200 mg/ml (see page 13 and 20). Yang teaches the antibody formulations are advantageous since they have lower viscosity and reduced aggregation (see page 13). Yang et al. teach that the concentrated antibody can be used to prepare pharmaceutical compositions containing antibody used at a variety of dilutions (see pages 17 and 18). Yang et al. teaches on page that:
“Concentrated antibody preparations prepared according to the present invention may be used to prepare pharmaceutical formulations by combining a concentrated antibody preparation consisting essentially of an aqueous solution of antibodies and histidine or acetate buffer at a concentration in the range of from about 2 mM to about 48 mM produced according to the disclosed invention with one or more pharmaceutically acceptable carriers to produce a pharmaceutical composition.”.
Yang teaches that said pharmaceutical compositions may be prepared to include one or more pharmaceutically acceptable carriers or pharmaceutically acceptable auxiliary substances as required, and that the pH of the compositions can be adjusted (see pages 17-18, in particular). Thus, the concentrations of the instant claims, such as about 160mg/ml, 30 mM histidine and a 5.5.pH fall entirely within the specific ranges taught by Yang.
Yang differs from the claimed invention in that it does not explicitly using sorbitol, mannitol, and a polysorbate surfactant as pharmaceutical carriers/auxiliary substances, nor does it teach veltuzumab as the anti-CD20 antibody.
Goldenberg et al. teaches the antibody veltuzumab and its wondrous and amazing properties (see Example 14 and [0049]).
The ‘689 patent teaches a method of preparing a therapeutic antibody comprising concentrating the antibody by diafiltration and ultrafiltration to at least 250 or l, and using the concentrated antibody to prepare a high concentration formulation of the antibody comprising polysorbate, said antibody formulation being used for administration to a patient in a solution (see claims 1-2, and abstract in particular). The ‘689 patent teaches that formulations of antibodies, including veltuzumab, wherein the antibodies can be formulated by the addition of a stabilizing agents such as mannitol and polysorbate, which protect antibodies against aggregation (see paragraph 126, 172, Table 3, and claim 24, in particular). For example, see Table 3 of the ‘689 patent which exemplifies a high concentration liquid formulation of veltuzumab at a concentration of 162 mg/ml (i.e. “about” 160 mg/ml), and containing polysorbate and mannitol at a pH of 5.2. The ‘689 patent teaches adding polysorbate after antibody concentration, and using a 0.1% concentration of polysorbate (i.e. 1 mg/ml, see the claims).
Andya et al. teach a method of making a pharmaceutical formulation of an antibody, such as veltuzumab (hA20, see [0365]) at a concentration of about 100 to 200 mg/ml, in a liquid formulation with an amino acid (see [0372] ). The amino acid (such as histidine) can be at a concentration of about 10 to about 40 mM, and have a pH of about 5.5 (see page 5 and 32-33). The formulation can comprise a surfactant such as polysorbate 20 (see [0376]) and a saccharide such sorbitol or mannitol (see [0102], [0375]). Andya teaches that said formulations are advantageous since they retard degradation of the antibody (see page 5 in particular). Andya teaches adding polysorbate can reduce insoluble aggregate formation, such as occurs upon shaking, and teaches a concentration of from 0.01% to about 0.1% (i.e. 0.1 mg/ml to 1 mg/ml, see claims and paragraph 376). Andya exemplifies a polysorbate concentration of 0.02%, i.e. 0.2 mg/ml, see examples.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have created the claimed invention to perform the method of Yang et al., with veltuzumab, because Goldenberg et al. teaches the antibody veltuzumab and its wondrous and amazing properties (see Example 14 and [0049]), and it would be obvious to perform the method made obvious by Yang et al. with veltuzumab as the type of CD20 antibody. One of ordinary skill in the art would have been motivated to do the aforementioned to obtain antibody at different desired concentrations as per Yang et al. without having to perform separate purifications for every desired concentration.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to add sorbitol/mannitol, and a polysorbate surfactant as taught by Andya and the ‘689 patent, as pharmaceutical carriers in the final pharmaceutical formulations of Yang, and to dilute the high concentration antibody with polysorbate and sorbitol/mannitol to achieve a final high concentration antibody comprising said polysorbate and sorbitol/mannitol. As the ‘689 patent teaches a desired concentration of 160 mg/ml or 162 mg/ml for veltuzumab, selecting this as a final concentration would be obvious. Furthermore, the ordinary artisan at the time the invention was made would have been motivated to include mannitol/sorbitol and polysorbate in the final formulation, since Andya and the ‘689 patent teach that mannitol/sorbitol and polysorbate can be added to liquid formulations of veltuzumab and act as stabilizing agents to protect against aggregation and degradation. For example, see Table 3 of the ‘689 patent which exemplifies a high concentration liquid formulation of veltuzumab at a concentration of 162 mg/ml (i.e. “about” 160 mg/ml), and containing polysorbate and mannitol at a pH of 5.2. Thus, the ordinary artisan would have reasonable expectation of success that mannitol and polysorbate can be added to CD20 antibody formulation of Yang, including to a veltuzumab antibody formulation, to achieve the advantages taught by the cited references (i.e. protection from aggregation and degradation). Adjusting the final pH to a desired level as taught by Andya would be well within the purview of the ordinary artisan. Furthermore, a pH of 5.5 +/- 0.1 would be obvious. For example, the ‘689 patent teaches an example of a veltuzumab formulation at pH 5.2, which is very close the lower limit pH range of the instant claims (5.4). Furthermore, both Andya and Yang teach pH values in the range of 5.5 and optimization to a pH range of 5.5 +/- 0.1 would be well within the purview of the ordinary artisan. Furthermore, the ‘689 patent teaches 0.1%, i.e. 1 mg/ml of polysorbate and Andya teaches adding polysorbate at a concentration of from 0.01% to about 0.1% (i.e. 0.1 mg/ml to 1 mg/ml, see claims). Andaya also teaches the use of a saccharide such as sorbitol or mannitol to reduce aggregate formulation, and that exemplary concentrations can range from about 10 mM to about 1 M, for example from about 60 mM to 250 mM. Given the molecular weight of sorbitol (182), the recited concentration of 40 mg/ml is equivalent to 220 mM. Thus, Andaya teaches concentrations overlapping with the concentration recited in the present clams, an in fact teaches a preferred embodiment of using 240 mM. This is very close to 40 mg/ml recited in the present claims. However, Andaya teaches that concentrations as low as 10 mM can be effective in reduce aggregation. See also the ‘689 patent which exemplifies a 12 mg/ml concentration of mannitol (see Table 3). Thus, optimizing the formulations to have a 40 mg/ml concentration to achieve reduced aggregation would be well within the purview of the ordinary artisan. Thus, the concentration in the instant claims falls within the range of concentrations taught in the prior art to be suitable for use as stabilizing agents in antibody formulations, rendering the instant claims obvious.
Applicant’s arguments filed 9/12/25 have been fully considered, but they are not persuasive.
Applicant argues that that the claims are not obvious for the reasons set forth above.
The claims stand rejected for the same reasons set forth above.
Claim 35 is rejected under 35 U.S.C. 103(a) as being unpatentable over . 9,468,689 (of record), Yang et al. (WO 2004/001007 A2) and U.S. 2006/0088523 (Andya et al., of record) OR over Yang et al. (WO 2004/001007 A2) Goldenberg et al. (WO 2010/011697 A1) and U.S. 2006/0088523 (Andya et al., of record), as applied to claims 12, 15, 17, 20-21, and 36 above, each in further view of WO 2011/090088, as evidenced by the English translation in national stage entry of the same application (US 2013/0022625).
The combined teachings of the cited references are discussed above.
They do not explicitly teach one or more amino acids selected from glutamic acid and aspartic acid.
WO 2011/090088 teaches antibody formulations that achieve significantly higher stabilizing effects, wherein the antibody formulations contain histidine buffer, and further contain a counter ion species selected from aspartic acid or glutamic acid (see page 1 of the translation). WO 2011/090088 teaches that including another amino acid, such as glutamic acid or aspartic acid in histidine buffers acts as a stabilizer to provide a stable highly concentrated antibody containing liquid formulation (see page 1 of the translation). WO 2011/090088 teaches using histidine buffer in the concentration of 5 to 50 mM, and that the formulation can further contain sorbitol in amounts from 10 to 300 mM and polysorbates 20 in amounts from 0.0001% to 10% (see pages 6-7 of the translation, in particular). WO 2011/090088 teaches that the pH range is preferably 5.5 to 6.5 (see page 7 of the translation). WO 2011/090088 teaches that the formulations are for use in antibody formulations having 150 mg/ml or 250g mg/ml antibody and that the antibodies used in the formulations are not particularly limited, as long as they bind to an antigen of interest (see page 3 of the translation, in particular).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to apply the teachings of WO 2011/090088, to the antibody formulations made obvious by the ‘689 patent, Yang, and Andya or by Yang, Andya and Goldenberg. One of ordinary skill in the art at the time the invention was made would have been motivated further include aspartic acid or glutamic acid, since WO 2011/090088 teaches that doing so further stabilizes histidine containing antibody formulations acts, since it acts as a counter ion species. Furthermore, the ordinary artisan would have a reasonable expectation of success, since WO 2011/090088 teaches that said glutamic acid/aspartic acid suitable for use in formulations comprising 5-50 mM histidine buffers that also contain polysorbate 20 and 10-300mM sorbitol, and that they are particular suited for formulating highly concentrated antibodies of any type.
Applicant’s arguments filed 9/12/25 have been fully considered, but they are not persuasive.
Applicant argues that that the claims are not obvious for the reasons set forth above.
The claims stand rejected for the same reasons set forth above.
The non statutory 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 12, 15, 17, 20-21, and 35-36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable claims 1, 4-6, 8, 12-16, 18-20, 22-23, 26-32 of copending Application No. 14/068,074 (reference application), in view of WO 2011/090088 (of record).
The ‘074 application claims a method of producing a liquid formulation of veltuzumab at consisting of about 160mg/ml veltuzumab, and comprising a buffer consisting of histidine, polysorbate 20 surfactant at a concentration of 0.1-0.2 mg/ml, 220 mM sorbitol (i.e. 40mg/ml). The ‘074 application claims histidine at 30 mM and a pH of 5.45. The ‘074 publication also claims a liquid formulation of veltuzumab comprising at least 160 ng/ml antibody, 220 mM sorbitol (i.e. 40mg/ml), 30 mM histidine, and 0.1mg/ml to 0.3 mg/ml polysorbate 20, having a pH of 5-6. Including one or more amino acids selected from glutamic acid and aspartic acid would be obvious based on WO 2011/090088 for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s statement that the rejection be held in abeyance is acknowledged.
No claim is allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
Prosecution Insights