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 .
Claim Status
The amendments and arguments filed 9/29/25 are acknowledged. Claims 4, 7, 10-11, 13, 15, and 17-18 are cancelled. Claims 1-3, 5-6, 8-9, and 14 are amended. Claims 1-3, 5-6, 8-9, 12, 14, and 16 are pending. Claims 1-3, 5-6, 8-9, 12, 14, and 16 are currently under consideration for patentability under 37 CFR 1.104.
Objections Withdrawn
The objection to the abstract of the disclosure because the term “α4β7 antibody” does not clearly indicate the invention is withdrawn in light of Applicant’s amendments thereto.
The objection to the use of the term PLURONIC and TWEEN, which is a trade name or a mark used in commerce is withdrawn in light of Applicant’s amendments thereto.
The objection to claim 1 because of the following informalities: the phrase “antibody comprising, buffer…” should not have a comma after the term “comprising” is withdrawn in light of Applicant’s amendments thereto.
The objection to claim 1 because of the following informalities: the term “PEG-400” contains an acronym and/or abbreviation that should be spelled out upon first occurrence is withdrawn in light of Applicant’s amendments thereto.
Claim Rejections Withdrawn
The rejection of claims 1-3, 5-6, 8-9, 12, 14, and 16 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 4, 7, 10-11, 13, 15, and 17-18 is rendered moot by cancellation of the claims.
The rejection of claims 1-3, 5-6, 8-9, 12, 14, and 16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 4, 7, 10-11, 13, 15, and 17-18 is rendered moot by cancellation of the claims.
The rejection of claims 3 and 6 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 4, 7, and 10-11 is rendered moot by cancellation of the claims.
The rejection of claim(s) 1-3, 8-9, 12, and 16 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(1) as being anticipated by Shenoy et al (WO 02/072636 A2; filed 12/26/01; published 9/19/02) is withdrawn in light of Applicant’s amendments thereto. The rejection of claims 4 and 10-11 is rendered moot by cancellation of the claims.
Claim Rejections Maintained
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claims 1-3, 5-6, 8-9, 12, 14, and 16 under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(1) as being anticipated by Shenoy (US 2018/0333493 A1; filed 6/20/17; published 11/22/18) is maintained. The rejection of claims 4, 7, 10-11, 13, 15, and 17-18 is rendered moot by cancellation of the claims.
The instant claims are directed to a stable pharmaceutical formulation of vedolizumab. The formulation comprises a buffer, PEG-400, arginine, salt and surfactant, and the formulation can be free of sugar and anti-oxidant. The buffer can be histidine or histidine-phosphate buffer. The formulation can be a liquid or a lyophilized formulation. The claims are also drawn toa method of controlling aggregates and charge variants of the vedolizumab formulation, comprising adding a buffer comprising PEG, salt, arginine, and surfactant to an antibody formulation. The surfactant can be polysorbate 80.
Regarding the limitations of instant claim 1, Shenoy teaches stable form compositions of an antibody (see e.g. paragraph [0162], [0592]), wherein the formulations can be stable for at least 40 °C for up to a month (see e.g. paragraph [0162]), wherein the antibody can be an anti-α4β7 antibody such as Vedolizumab (see e.g. paragraph [0195], [0592], [0683], [0688],Example 37). The formulation can comprise a buffer such as histidine (see e.g. paragraph [0014], [0018],[0022], [0026], [0038]), a polyethylene glycol such as PEG-400 (see e.g. paragraph [0147]), excipients such as arginine (see e.g. paragraph [0039], [0043], [0045] ), salts (see e.g. paragraph [0044], [0214], [0218], [0255]), and surfactants such as polysorbates or poloxamer (see e.g. paragraph [0044], [0215], [0227], [0241], [0247], [0251]). A preferred embodiment includes protein concentration of 100, 150, 200 mg/ml (see e.g. paragraph [0010]). Shenoy teaches stable form compositions of an antibody (see e.g. paragraph [0162], [0592]), wherein the antibody can be an anti-α4β7 antibody such as Vedolizumab (see e.g. paragraph [0195], [0592], [0683], [0688], Example 37).
Regarding the limitations of instant claim 2, the formulation can comprise a buffer such as histidine (see e.g. paragraph [0014], [0018],[0022], [0026], [0038])
Regarding the limitations of claim 3, the functional properties as recited in the instant claims are inherent in a composition comprising identical components to those of claim 1, from which claims 3 and 4 depend. Shenoy teaches a composition comprising the same antibody concentration in the same formulation comprising the same components as compared to instant claim 1. The functional characteristics recited in the instant claims would therefore be inherently present in the composition of Shenoy.
Regarding the limitations of instant claim 5, the formulation can comprise 150 mg/ml of a protein agent such as the antibody (see e.g. paragraph [0010]). The instant specification does not define the term “about”, but states that “The term "about" refers to a range of values that are similar to the stated reference value and includes a range of values that fall within 20 % or less, of the stated reference value.” The 150 mg/ml of Shenoy would fall within 20% or less variation from the recited 160 mg/ml of antibody of instant claim 5. The formulation can comprise a buffer such as histidine (see e.g. paragraph [0014], [0018],[0022], [0026], [0038]). The formulation can comprise a polyethylene glycol such as PEG-400 (see e.g. paragraph [0147]), which can be a viscosity reducing agent (see e.g. paragraph [0044]), wherein viscosity reducing agents can be present at about 10% w/v (see e.g. paragraph [0119]). The formulation can comprise viscosity reducing agents such as arginine (see e.g. paragraph [0039], [0043], [0045] ), wherein the viscosity reducing agents can be present at about 100 mM (see e.g. paragraph [0049]). The 100 mg/ml of Shenoy would fall within 20% or less variation from the recited 120 mg/ml of arginine in instant claim 5. The formulation can comprise viscosity reducing agents such as salts like sodium chloride paragraph (see e.g. paragraph [0044], [0214], [0218], [0255]), wherein the viscosity reducing agents can be present at about 50 mM (see e.g. paragraph [0049]). Shenoy teaches a composition that can comprise a detergent such as polysorbate 80 (see e.g. paragraph [0044], [0215], [0241]).
Regarding the limitations of claim 6, the functional properties as recited in the instant claims are inherent in a composition comprising identical components to those of claim 5, from which claims 6-7 depend. Shenoy teaches a method for manufacturing a composition comprising the same antibody concentration in the same formulation comprising the same components as compared to instant claim 5. The functional characteristics recited in the instant claims would therefore be inherently present in the composition and method of manufacture described in Shenoy.
Regarding the limitations of instant claim 8 and 14, the formulation can be in aqueous or lyophilized form (see e.g. paragraph [0168], [0286], [0287]).
Regarding the limitation of instant claim 9, the disclosure of Shenoy also includes methods of making (see e.g. paragraph [0002], [0062], [0174]). he functional properties as recited in the instant claims are inherent in a composition comprising identical components to those of claim 9. Shenoy teaches a method for manufacturing a composition comprising the same antibody concentration in the same formulation comprising the same components as compared to instant claim 9. The functional characteristics recited in the instant claims would therefore be inherently present in the composition and method of manufacture described in Shenoy.
Regarding the limitation of instant claim 12 and 16, Shenoy teaches a composition that can comprise a detergent such as polysorbate 80 (see e.g. paragraph [0044], [0215], [0241]).
Applicant’s Arguments
Applicant argues:
1. Applicant recites two passages from Shenoy that Applicant argues shows that “it is clear that the formulations disclosed in Shenoy must include sugars, sugar alcohols, and antioxidants”. Therefore Applicant argues that Shenoy teaches away from the instant invention, which discourages use of sugars and anti-oxidants.
2. Vedolizumab is only one of many products listed in Shenoy, and the Examiner picks isolated passages that are inconsistent with the reference’s broader teachings.
3. Shenoy fails to provide sufficient guidance on how to make and use the compound, and fails to provide specific data or examples using vedolizumab. Therefore the reference is not enabling.
Applicant’s arguments have been fully considered and are not persuasive for the following reasons:
1. Shenoy does not teach away from the instant invention. Shenoy provides alternative possible species, but does not require that every formulation that is encompassed must have sugars, sugar alcohols or antioxidants. Even the Shenoy passages identified by Applicant refer to the components in the alternative, for example claim 3 of Shenoy recites the phrase “comprising one or more excipients, including…” This means that the formulation could have one of the species, or more of the species. In other words, Shenoy specifically allows for combinations of components that do not include sugars, sugar alcohols or anti-oxidants. The terminology used by Shenoy does not require that all of the listed species are present simultaneously. In claim 20 of Shenoy, the selected passage states “wherein the excipients or additives are chosen from a group consisting of…and combinations thereof”. This indicates a Markush grouping, where the listed species are alternatives (see MPEP 803.02 for guidance on Markush groupings, which lists the appropriate language for such a grouping as including “selected from the group consisting of,” which is similar to the language of Shenoy). The Shenoy language very clearly refers to alternatives of species, which refers to a genus of compositions, which each contain different combinations of components. In paragraph [0295], Shenoy also presents the same type of Markush language, identifying possible alternatives for the formulation. MPEP 2123 states that 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). 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). MPEP 2141.02 also states that "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).
2. Regarding the “cherry pick[ing]” argument, the instant claims recites the same components that are listed as possible alternative components in Shenoy, as indicated in the rejection. MPEP 2131.02 states that when the species is clearly named in a reference, the species claim is anticipated no matter how many other species are additionally named. Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that “the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is ‘described’ as that term is used in 35 U.S.C. § 102(a), in that publication.”). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982) (The claims were directed to polycarbonate containing cadmium laurate as an additive. The court upheld the Board’s finding that a reference specifically naming cadmium laurate as an additive amongst a list of many suitable salts in polycarbonate resin anticipated the claims. The applicant had argued that cadmium laurate was only disclosed as representative of the salts and was expected to have the same properties as the other salts listed while, as shown in the application, cadmium laurate had unexpected properties. The court held that it did not matter that the salt was not disclosed as being preferred, the reference still anticipated the claims and because the claim was anticipated, the unexpected properties were immaterial.). The formulation components in the Shenoy reference are identical to those listed in the instant claims, and they have a similar intended purpose. Therefore the compositions of the instant claims are anticipated.
3. As stated in MPEP 2152.02(b), while the conditions for patentability of AIA 35 U.S.C. 112(a) require a written description of the claimed invention that would have enabled a person skilled in the art to make as well as use the invention, the prior art provisions of AIA 35 U.S.C. 102(a)(1) and (a)(2) require only that the claimed invention is “described” in a prior art document (patent, published patent application, or printed publication). The two basic requirements that must be met by a prior art document in order to describe a claimed invention such that it is anticipated under AIA 35 U.S.C. 102 are the same as those under pre-AIA 35 U.S.C. 102. First, “each and every element of the claimed invention” must be disclosed either explicitly or inherently, and the elements must be “arranged or combined in the same way as in the claim.” See In re Gleave, 560 F.3d 1331, 1334, 90 USPQ2d 1235, 1237-38 (Fed. Cir. 2009), citing Eli Lilly & Co. v. Zenith Goldline Pharms., Inc., 471 F.3d 1369, 1375, 81 USPQ2d 1324,1328 (Fed. Cir. 2006); Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1370, 88 USPQ2d 1751, 1759 (Fed. Cir. 2008); In re Bond, 910 F.2d 831, 832-33, 15 USPQ2d 1566, 1567 (Fed. Cir. 1990). The facts of the Shenoy reference meet this test, because the components of the instant compositions are described in the Shenoy reference, and are combined into one formulation for the same purpose, which is to stabilize a protein formulation. Second, a person of ordinary skill in the art must have been enabled to make the invention without undue experimentation. See Gleave, 560 F.3d at 1334, 90 USPQ2d at 1238 (citing Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312, 1314, 88 USPQ2d 1381, 1383 (Fed. Cir. 2008), and In re LeGrice, 301 F.2d 929, 940-44, 133 USPQ 365, 372 (CCPA 1962)). Thus, in order for a prior art document to describe a claimed invention such that it is anticipated under AIA 35 U.S.C. 102(a)(1) or (a)(2), it must disclose all elements of the claimed invention arranged as they are in the claim, and also provide sufficient guidance to enable a person skilled in the art to make the claimed invention. There is, however, no requirement that a prior art document meet the “how to use” requirement of 35 U.S.C. 112(a) in order to qualify as prior art. See Gleave, 560 F.3d at 1334, 90 USPQ2d at 1237-38. As described above, Shenoy specifically describes the creation of a formulation that can include vedolizumab, wherein all of the same components are anticipated for combining into a single protein formulation. Shenoy specifically discloses the intention of the composition to address “high viscosity and/or… aggregation” of a “highly concentrated protein-agent formulation[]” (see e.g. paragraph [0002]). The elements of the instant claimed composition are all described and can be combined using conventional methods. Therefore Shenoy has provided both the description of the components, and has described how to make the compositions.
Further, there is no requirement for the reference to have a specific example or data in order to fully describe the claimed invention. As stated in MPEP 2131.02, a reference disclosure can anticipate a claim when the reference describes the limitations but "'d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting Tool Co., 780 F.3d 1376, 1381, 114 USPQ2d 1250, 1254 (Fed. Cir. 2015) (quoting In re Petering, 301 F.2d 676, 681(CCPA 1962)). The species of components for the instant formulation are specifically identified in Shenoy, and Shenoy displays a specific intention to combine components to achieve stability for a protein formulation. One of skill in the art could immediately envisage the possible combinations, and therefore the disclosure of Shenoy anticipates all of the encompassed combinations of disclosed component species. Additionally, Applicant is reminded, as stated in MPEP 2123, that "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
New Claim Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3 and 6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3 and 6 have been amended to read “vedolizumab is stored” which recites a method step. However, the claim preamble is directed to a formulation, which is a composition. It is therefore unclear whether the invention encompasses a composition or a method. It is recommended that Applicant consider amending the claim to remove the active method step language, such as “vedolizumab has been
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANDREA K MCCOLLUM/Examiner, Art Unit 1674
/BRIAN GANGLE/Primary Examiner, Art Unit 1645