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 .
Information Disclosure Statement
The information disclosure statements (IDS) filed 08/07/2023 and 05/29/2026 have been considered and the references therein are of record.
Response to Amendment
Applicant’s amendments and remarks filed 05/29/2026 are acknowledged. Claims 1 and 24 are amended. Claims 59-70 are new. Claims 2, 4, 7, 9, 11, 13, 25-46, and 48-51 were previously canceled. Claims 17-22 and 55-56 are newly canceled. Claims 1, 3, 5, 6, 8, 10, 12, 14-16, 23, 24, 47, 52-54, and 57-70 are under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Objections Withdrawn
Claim Objections
The objection to the claims for missing status identifiers is withdrawn in response to Applicant’s amendment to the claims, which added appropriate status identifiers to canceled claims 25-46 and 48-51.
Rejections Withdrawn
All previous rejections of claims 17-22 and 55-56 are hereby withdrawn in response to Applicant’s cancelation of claims 17-22 and 55-56.
Double Patenting
The non-statutory double patenting rejection of instant claims 1, 3, 5-6, 8, 10, 12, 14-24, 47, and 52-58 as being unpatentable over claim 24 of U.S. Patent No. 10308720B2 is withdrawn in response to Applicant’s arguments and upon further consideration.
The provisional non-statutory double patenting rejection of instant claims 53 and 54 as being unpatentable over claims 22-25 and 51-54 of co-pending application No. 18/853278 is withdrawn upon further consideration.
The provisional non-statutory double patenting rejection of instant claims 53 and 54 as being unpatentable over claims 22-25 of co-pending application No. 18/865854 is withdrawn upon further consideration.
Response to Arguments
In response to the non-statutory double patenting rejection over U.S. Patent No. 10308720B2 made in the Office Action mailed 03/02/2026, Applicant argues:
“Obviousness-type double patenting (ODP) analysis requires a determination of whether the later claims are anticipated by, or obvious over, the earlier claims. Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955, 967-72 (Fed.Cir. 2001). Obviousness-type double patenting can be found when the claims of the later patent or application are not patentably distinct (anticipated or obvious) in view of the claims of the first patent or application. For example, ODP may be found where a patented claim to a species "anticipates" a later genus claim encompassing that species. In re Metoprolol Succinate Patent Litig., 494 F. 3d 1011, 1019 (Fed. Cir. 2007) (finding ODP where a claim to a composition comprising metoprolol succinate rendered a later patent to "metoprolol succinate" invalid for ODP). But that is not the case here.
Similar to § 102 prior art, anticipation in ODP requires that all elements of the claimed invention must be present in a single prior art reference. For claim 24 to "anticipate" instant claims 1, 3, 5-6, 8, 10, 12, 14, 24, 47 and 52-58 as alleged, claim 24 would have to disclose each and every limitation of the rejected claims, e.g., claim 24 would need to disclose a pharmaceutical formulation comprising not only SEQ ID NO: 7, but also comprising 20-70 mg/mL DR5-binding polypeptide, 5-20 mM histidine, 7-10% w/v sucrose, and 0.1-0.8% poloxamer P188 at a pH of 5.3-6.7. Thus, claim 24 of the '720 patent does not anticipate any of the pending claims which all require those components.
It is improper to consult the specification of a reference cited in an ODP rejection beyond what is necessary to construe the claims. Here, only a cursory review of the sequence table in the specification is necessary. But even if it were proper to consult the '720 specification as a whole, the claimed formulation comprising SEQ ID NO: 7 and recited components are not disclosed anywhere in the '720 specification.
The rejected claims are also not obvious over the '720 claims, either. The normal § 103 analysis applies to determining whether the claims are patentably distinct over claim 24 of the '720 patent, namely, (i) determining the scope and content of a patent claim relative to a claim in the application at issue; (ii) determining the differences between the scope and content of the patent claim as determined in (i) and the claim in the application at issue; (iii) determining the level of ordinary skill in the pertinent art; and (iv) evaluating any objective indicia of non- obviousness.
Here, none of the '720 claims even recite a composition, let alone a formulation comprising the components recited in the specific concentrations as presently claimed. Cf In re Metoprolol Succinate Patent Litig., 494 F. 3d at 1019 ("Specifically, the earlier patent not only discloses but also claims a composition comprised-in-part of metoprolol succinate."). There is no rationale explaining how a person of ordinary skill (or even highly skilled) could arrive at the presently claimed formulation from claim 24 of the '720 patent. Like obviousness, ODP requires an articulated reason to modify prior art with a reasonable expectation of success. Eli Lilly and Co. et al. v. Teva Parenteral Medicines et al., 689 F3d 1368 (Fed. Cir. 2012).
Lastly, there is no improper extension of patent term for SEQ ID NO: 7 upon allowance of the instant claims. The claimed formulation comprising the polypeptide does not improperly extend the patent term for the polypeptide itself.”
This has been fully considered and is found to be persuasive. Claim 24 of the '720 patent does not directly anticipate the pending claims because the pending claims require the pharmaceutical formulation components. Since the instant pending claims require the antibody and the pharmaceutical formulation components, the '720 patent would have to also state the pharmaceutical formulation components to anticipate the instant pending claims. Therefore, the non-statutory double patenting rejection made over U.S. Patent No. 10308720B2 in the Office Action mailed 03/02/2026 is withdrawn.
In response to the provisional non-statutory double patenting rejection over co-pending application No. 18/853278 made in the Office Action mailed 03/02/2026, Applicant argues:
“The '278 application is not a proper reference to support a nonstatutory double patenting rejection because the effective filing date of the '278 application is after the effective filing date of the present application. The Examiner's allegation that the claims 53 and 54 anticipate the claims of the '278 is not a proper double patenting rejection of the instant claims which were filed earlier. MPEP § 804 states that where a provisional nonstatutory double patenting rejection is made, and one application has an earlier effective filing, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent. See MPEP § 804 (I)(B)(1)(b)(i). And again, there is no indication that a patent issuing from the present application would expire after the expiration of a patent issuing from the '278 application. Thus, there is no unjustified or improper timewise extension of the right to exclude if the present claims are allowed, which is the public policy behind the doctrine of double patenting. MPEP § 804.01.”
This has been fully considered, but is not found to be persuasive. The nonstatutory double patenting rejection is not improper because it is not the only rejection remaining. MPEP § 804 (I)(B)(1)(b)(i) states, “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent.” Since the 103 rejection is maintained (as outlined below), the new provisional nonstatutory double patenting rejection (also outlined below) is not the only rejection remaining.
The provisional non-statutory double patenting rejection over co-pending application No. 18/853278 made in the Office Action mailed 03/02/2026 is withdrawn upon further consideration because the '278 application does not directly anticipate the pending claims because the pending claims require the pharmaceutical formulation components. Since the instant pending claims require the antibody and the pharmaceutical formulation components, the '278 application would have to also state the pharmaceutical formulation components to anticipate the instant pending claims.
In response to the provisional non-statutory double patenting rejection over co-pending application No. 18/865854, Applicant argues:
“The '854 application is not a proper reference to support a nonstatutory double patenting rejection because the effective filing date of the '854 application is after the effective filing date of the present application. The Examiner's allegation that the claims 53 and 54 anticipate the claims of the '854 is not a proper double patenting rejection of the instant claims which were filed earlier. MPEP § 804 states that where a provisional nonstatutory double patenting rejection is made, and one application has an earlier effective filing, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent. See MPEP § 804 (I)(B)(1)(b)(i). And again, there is no indication that a patent issuing from the present application would expire after the expiration of a patent issuing from the later-filed '854 application. Thus, there is no unjustified or improper timewise extension of the right to exclude if the present claims are allowed, which is the public policy behind the doctrine of double patenting. MPEP § 804.01.”
This has been fully considered, but is not found to be persuasive. The nonstatutory double patenting rejection is not improper because it is not the only rejection remaining. MPEP § 804 (I)(B)(1)(b)(i) states, “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent.” Since the 103 rejection is maintained (as outlined below), the new provisional nonstatutory double patenting rejection (also outlined below) is not the only rejection remaining.
The provisional non-statutory double patenting rejection over co-pending application No. 18/865854 made in the Office Action mailed 03/02/2026 is withdrawn upon further consideration because the '854 application does not directly anticipate the pending claims because the pending claims require the pharmaceutical formulation components. Since the instant pending claims require the antibody and the pharmaceutical formulation components, the '854 application would have to also state the pharmaceutical formulation components to anticipate the instant pending claims.
Rejections Maintained
Claim Rejections - 35 USC § 103
The rejection of claims 1, 3, 5-6, 8, 10, 12, 14-16, 23-24, 47, 52-54, and 57-58 under 35 U.S.C. 103 as being unpatentable over Timmer et al. 2019 (US10308720B2) in view of Alder et al. 2011 (WO2011012637A2) is maintained and claims 59-70 are newly rejected. This is a modified rejection necessitated by Applicant’s amendments to the claims in the response filed 05/29/2026.
The instant claims are drawn to a pharmaceutical formulation composition comprising 50 mg/ml DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, and 0.2% poloxamer P188, and wherein the pH of the formulation is about 6. Some formulations also include 5 mM methionine, a lyophilized formulation formed by lyophilizing the pharmaceutical formulation, and a pharmaceutical formulation formed by reconstituting the lyophilized formulation in water. The instant claims also include a method of treating cancer with the composition, where the cancer is chondrosarcoma, mesothelioma, colorectal cancer, Ewing sarcoma, or pancreatic adenocarcinoma. The DR5-binding polypeptide has SEQ ID NO: 7, which as the structure of VHH-Linker1-VHH-Linker2-Hinge-Fc.
Timmer teaches a DR5-binding polypeptide with a structure of VHH-Linker1-VHH-Linker2-Hinge-Fc that has identical sequence to instant SEQ ID NOs: 7. Timmer SEQ ID NO: 113 teaches a VHH-Linker1-VHH-Linker2-Hinge and Timmer SEQ ID NO: 2 teaches a Fc domain, which collectively have an identical sequence to instant SEQ ID NO: 7. Timmer explicitly teaches SEQ ID NOs: 113 and 2 being joined together to make the DR5-binding polypeptide that’s claimed in instant SEQ ID NO: 7 (claim 24). Timmer teaches a method of treating a subject with cancer by administering the DR5-binding polypeptide, where the cancer is sarcoma, mesothelioma, colorectal cancer, or pancreatic cancer (column 43, lines 21-30). The alignment data between Timmer SEQ ID NOs: 113 and 2 and instant SEQ ID NO: 7 is shown below. Timmer SEQ ID NO: 113 spans from position 1Db to 265Db. Timmer SEQ ID NO: 2 spans from position 266Db to 480Db. Instant SEQ ID NO: 7 spans from position 1Qy to 480Qy and contains instant SEQ ID NOs: 1-6.
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Timmer does not explicitly teach the pharmaceutical formulation beyond the DR5-binding polypeptide.
Alder teaches an anti-HER2 antibody composition comprising 50 to 350 mg/ml anti-HER2 antibody, about 1 to 100 mM histidine/HCl, about 1 to 500 mM sucrose, 5 to 25 mM methionine, 0.01 to 0.1% polyethylene-polypropylene copolymer (specifically Poloxamer 188), with a pH ranging from 5.5 +/- 2 that can be administered to patients as a cancer treatment (page 4). Some formulations also include a lyophilized formulation formed by lyophilizing the pharmaceutical formulation (claim 18), and a pharmaceutical formulation formed by reconstituting the lyophilized formulation in water (page 11, line 29-33 to page 12, line 1-6).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention from the disclosures of Timmer and Alder. One with ordinary skill in the art would have found it obvious to combine the DR5-binding polypeptide of Timmer with the antibody formulation of Alder to make the claimed composition because Alder teaches that the combination of ingredients creates a stable formulation for pharmaceutically active antibodies for therapeutic use and that this stable formulation can be both effectively lyophilized and reconstituted in water. As Timmer does not teach a formulation for DR5-binding polypeptide, an ordinary artisan would be motivated to use the antibody formulation of Alder to create a stable and pharmaceutically acceptable antibody formulation so that the DR5-binding polypeptide can be used to treat cancer patients. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
The prior art only differs from the claimed invention with respect to the claimed concentration amounts and/or ranges of the ingredients in the formulation. The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention because an ordinary artisan would have found it obvious to optimize the formulation through routine experimentation. An ordinary artisan would have been motivated to optimize the formulation to make the most stable and effective composition. MPEP 2144 sets forth Applicant’s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because the specification teaches effective embodiments of the claimed invention with 20-70 mg/ml DR5-binding polypeptide, 5.3-6.7 pH, 5-20 mM histidine HCl, 7-10% sucrose, 0.1-0.8% poloxamer 188, and 1-10mM methionine (para[0095-0099]; embodiment 11), which is evidence of noncriticality to the claimed invention. Thus, the claims do not contribute anything non-obvious over the prior art.
Response to Arguments
Applicant argues:
“Applicant respectfully submits that the amended claims 1 and 24 are not obvious over Timmer and Alder for at least the following reasons. Timmer teaches isolated polypeptides that bind death receptor 5 (DR5); however, Timmer does not teach a pharmaceutical formulation comprising a DR5-binding polypeptide comprising 20-70 mg/mL DR5-binding polypeptide, 5- 20 mM histidine, 7-10% w/v sucrose, and 0.1-0.8% poloxamer P188, as presently claimed. The Examiner acknowledged that Timmer "does not explicitly teach the pharmaceutical formulation beyond the DR5-binding polypeptide." Action, page 5.
Applicant submits that Alder does not cure the deficiencies of Timmer. Alder discloses a highly concentrated formulation of a pharmaceutically active anti-HER2 antibody for subcutaneous injection. See e.g., Alder, abstract. Alder states that "[t]he preparation of high concentration protein formulations is rather challenging and there is a need to adapt each formulation to the particular proteins used because each protein has a different aggregation behavior." (Emphasis Added) See Alder, page 3. Alder states that "[w]hile antibodies have a very similar overall structure, such antibodies differ in the amino acid composition (in particular in the CDR regions...and the glycosylation pattern" suggesting the need to adapt each formulation to the particular protein. Id. Alder addresses the problem of high viscosity of antibody formulations at high concentrations. See e.g., Alder, page 3. Alder is completely silent regarding formulations for VHH domain polypeptides, such as those presently claimed, which are significantly smaller in size as compared to antibodies.
Moreover, as disclosed in the present application, a Phase I formulation of INBRX-109, which contained 20 mg/ml polypeptide (significantly less than the Alder's concentration of 50- 350 mg/ml antibody), was unexpectedly "found to develop visible proteinaceous particles after 6months at oC." See paragraph [0118] of specification. The presently claimed invention solvesan unrecognized problem that is, the presently claimed DR5-binding polypeptide is not stable in all formulations composed of ingredients drawn from generally suitable lists of excipients, such as those disclosed in Alder.
A person having ordinary skill in the art would not have arrived at the claimed pharmaceutical formulation from Timmer alone or in combination with Alder, as there is no recognition of the problem in either Timmer or Alder, and even arguendo, a problem was recognized, a person of ordinary skill would not have predicted from Alder or from routine experimentation or "mere optimization", which conditions would work to reduce aggregation of the 1NBRX-109 formulation.
Moreover, the Examiner has not articulated how a person of ordinary skill in the art would arrive at the specific concentrations of components even if the references could be combined. "Whether a rejection is based on combining disclosures from multiple references, combining multiple embodiments from a single reference, or selecting from large lists of elements in a single reference, there must be a motivation to make the combination and a reasonable expectation that such a combination would be successful, otherwise a skilled artisan would not arrive at the claimed combination." In re Stepan Co., 868 F.3d 1342 (Fed. Cir. 2017)(emphasis added). Obviousness requires a motivation to do more than simply vary all parameters or try all possible choices until success is achieved. Id. at 1345 (Fed. Cir. 2017). In Stepan, the Federal Circuit reversed a determination that a formulation comprising a specific combination of components to result in a formulation having a "cloud point" above 700 C would have been obvious, stating that it is not the Applicant who must demonstrate the criticality of a specific parameter in the claims, absent evidence that a person of ordinary skill would have legitimate reason to "optimize" the prior art in the way the Office alleges. Id. at 1345.
Here, there is no articulation why a skilled artisan would, for example, specifically select 5-20 mM histidine from the broad 1 to 100 mM range Alder discloses, or 0.1% to 0.8% Poloxamer from the 0.01% to 0.1% Poloxamer Alder discloses. Very broad disclosures fail to provide the required motivation to narrow to a specific range. In Stepan, supra, the Federal Circuit held conclusory allegations of "routine optimization" was insufficient to support a conclusion of obviousness.
Additionally, the specification demonstrates that the claimed pharmaceutical formulation yields superior technical advantages. It was found, for example, that the claimed formulation comprising "sucrose was superior to [formulations comprising] trehalose," which is the preferred agent used in all 25 formulations in Alder. See, present specification, Table 1 and [00122]. See also, Table 4: Formulations A-Y, Examples 1 and 2 of Alder. The present specification also demonstrates that the final formulation differed in several other ways from the Phase I formulation, including the use of histidine rather than acetate, and a higher pH. These data show that the claimed formulation is not an arbitrary optimization but instead represents a non-obvious formulation of INBRX-109 suitable for long term storage.
A person of ordinary skill in the art would not have arrived at the particular formulation presently claimed with an expectation of success on the basis of Timer alone, or in combination with Alder, because Alder does not recognize the problem that DR5-binding polypeptide comprising VHH domains, is not stable in all formulations.
Accordingly, for at least the reasons stated above, claims 1, 24, and their dependent claims would not have been obvious over Timmer and Alder.”
This has been fully considered, but is not found to be persuasive.
First, the specification teaches that effective embodiments of the claimed invention overlap with those taught by Alder. The concentration of 20-70 mg/ml DR5-binding polypeptide overlaps with the 50 to 350 mg/ml anti-HER2 antibody concentration taught by Alder. The concentration of 5-20 mM histidine HCl overlaps with the about 1 to 100 mM histidine/HCl concentration taught by Alder. The concentration of 7-10% sucrose (w/v; which converts to about 204 mM to 292 mM) overlaps with the about 1 to 500 mM sucrose concentration taught by Alder. The concentration of 0.1-0.8% poloxamer 188 overlaps with the about 0.01 to 0.1% poloxamer 188 concentration taught by Alder. The concentration of 1-10mM methionine overlaps with the about 5-25 mM methionine concentration taught by Alder. The pH of 5.3-6.7 overlaps with the 5.5 +/- 2 pH taught by Alder. MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists.”
In regards to Applicant’s arguments that Alder teaches a “highly concentrated” antibody formulation and not a VHH domain polypeptide formulation, both antibodies and VHH domains are binding polypeptides and the ‘high concentration’ that Applicant alleges overlaps with the concentrations that Applicant has disclosed as functional embodiments of there claimed invention.
In regards to Applicant’s arguments that the claimed invention solves the problem of visible proteinaceous particles after 6 months at 5 degrees Celsius, there would be no expectation of reasonable success, and that there would be no motivation to optimize the formulation for the DR5-binding polypeptide, it would be obvious to an ordinary artisan that the formulation taught by Alder would require routine optimization to make the most stable composition. Applicant explicitly cites a direct teaching of Alder (“there is a need to adapt each formulation to the particular proteins used because each protein has a different aggregation” [Alder, page 3]) that would motivate an ordinary artisan to try various alternations to the formulas concentrations that would make the most stable composition. Yet, even without this explicit teaching by Alder, an ordinary artisan would have found it obvious to optimize the concentrations of the components in the formulation, and would have a reasonable expectation of success in doing so, because Alder teaches effective ranges for the components and an ordinary artisan would find it logical that these concentrations could be readily altered to specific amounts in the pursuit of making the most stable composition. Said another way, the broad ranges would motivate an ordinary artisan to optimize each range to work best for their specific binding polypeptide.
In regards to Applicant’s arguments that the instant specification demonstrates the finding that sucrose was superior to trehalose and to use histidine instead of acetate, neither of these results are unexpected because Alder already teaches both of these in an effective pharmaceutical formulation of a binding polypeptide. It is not “unexpected” to show that a known embodiment (one that is already taught by the prior art to be effective) is effective. Altering the concentrations in a way that still overlaps with the concentrations that are taught to be effective is neither novel or non-obvious, especially when the prior art does not teach the particular amount/range is critical and doesn’t teach away from the particular amount/range.
For all of these reasons, it would be obvious to an ordinary artisan to optimize the formulation taught by Alder to be used with the binding polypeptide taught by Timmer and an ordinary artisan would have had a reasonable expectation of success in doing so.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
New claim 23 is rejected 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. Upon the amendment of claim 1 to recite SEQ ID NO: 7, claim 23 fails to further limit claim 1 because claim 23 only requires the limitation of SEQ ID NO: 7. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Double Patenting
Claims 1, 3, 5-6, 8, 10, 12, 14-16, 23-24, 47, 52, 57-58, 63-64, and 67-68 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 24 of U.S. Patent No. 10308720B2 in view of Alder et al. 2011 (WO2011012637A2). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claims recite a DR5-binding polypeptide in a pharmaceutical composition, comprising SEQ ID NOs: 7.
Patented claim 24 recites an isolated polypeptide that binds DR5, comprising SEQ ID NO: 113 fused to SEQ ID NO: 2.
Instant SEQ ID NO: 7 has the identical sequence to the fusion protein of SEQ ID NOs: 113 and 2 in patented claim 24. However, patented claim 24 does not explicitly teach the pharmaceutical formulation beyond the DR5-binding polypeptide.
Alder teaches an anti-HER2 antibody composition comprising 50 to 350 mg/ml anti-HER2 antibody, about 1 to 100 mM histidine/HCl, about 1 to 500 mM sucrose, 5 to 25 mM methionine, 0.01 to 0.1% polyethylene-polypropylene copolymer (specifically Poloxamer 188), with a pH ranging from 5.5 +/- 2 that can be administered to patients as a cancer treatment (page 4). Some formulations also include a lyophilized formulation formed by lyophilizing the pharmaceutical formulation (claim 18), and a pharmaceutical formulation formed by reconstituting the lyophilized formulation in water (page 11, line 29-33 to page 12, line 1-6).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention by formulating the antibody of patented claim 24 in the pharmaceutical composition of Alder. One with ordinary skill in the art would have found it obvious to combine the DR5-binding polypeptide with the antibody formulation of Alder to make the claimed composition because Alder teaches that the combination of ingredients creates a stable formulation for pharmaceutically active binding polypeptides for therapeutic use and that this stable formulation can be both effectively lyophilized and reconstituted in water. As U.S. Patent No. 10308720B2 does not teach a formulation for DR5-binding polypeptide, an ordinary artisan would be motivated to use the antibody formulation of Alder to create a stable and pharmaceutically acceptable antibody formulation so that the DR5-binding polypeptide can be used to treat cancer patients. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Further, regarding the specific concentrations for all of the components of the composition, these are art recognized variables and therefore, one would engage in routine optimization to obtain the desired result of a stable formulation for the composition, thus arriving at these specific concentrations as claimed. See MPEP 2144.05 (II). The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention because an ordinary artisan would have found it obvious to optimize the formulation through routine experimentation. An ordinary artisan would have been motivated to optimize the formulation to make the most stable and effective composition. MPEP 2144 sets forth Applicant’s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because the specification teaches effective embodiments of the claimed invention with 20-70 mg/ml DR5-binding polypeptide, 5.3-6.7 pH, 5-20 mM histidine HCl, 7-10% sucrose, 0.1-0.8% poloxamer 188, and 1-10mM methionine (para[0095-0099]; embodiment 11), which is evidence of noncriticality to the claimed invention.
Claims 53, 54, 59-62, 66, and 70 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-25 and 51-54 of co-pending application No. 18/853278 in view of Alder et al. 2011 (WO2011012637A2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to a method of treating cancer using the DR5-binding polypeptide in a pharmaceutical composition, comprising SEQ ID NOs: 7, recited above.
The co-pending claims recite a DR5 agonist administered with a PLK1 inhibitor or a CDK inhibitor to treat cancer, where the DR5 agonist has SEQ ID NO: 7, and specifies that the DR5 agonist can be administered separately from the PLK1 inhibitor or CDK inhibitor. Therefore, the co-pending claims are drawn to the DR5 agonist with SEQ ID NO: 7 being administered alone to treat cancer.
Instant SEQ ID NO: 7 has identical sequence to co-pending SEQ ID NO: 7. However, the co-pending claims do not explicitly teach the pharmaceutical formulation beyond the DR5-binding polypeptide.
Alder teaches an anti-HER2 antibody composition comprising 50 to 350 mg/ml anti-HER2 antibody, about 1 to 100 mM histidine/HCl, about 1 to 500 mM sucrose, 5 to 25 mM methionine, 0.01 to 0.1% polyethylene-polypropylene copolymer (specifically Poloxamer 188), with a pH ranging from 5.5 +/- 2 that can be administered to patients as a cancer treatment (page 4). Some formulations also include a lyophilized formulation formed by lyophilizing the pharmaceutical formulation (claim 18), and a pharmaceutical formulation formed by reconstituting the lyophilized formulation in water (page 11, line 29-33 to page 12, line 1-6).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention by formulating the antibody of patented claim 24 in the pharmaceutical composition of Alder. One with ordinary skill in the art would have found it obvious to combine the DR5-binding polypeptide with the antibody formulation of Alder to make the claimed composition because Alder teaches that the combination of ingredients creates a stable formulation for pharmaceutically active antibodies for therapeutic use and that this stable formulation can be both effectively lyophilized and reconstituted in water. As U.S. Patent No. 10308720B2 does not teach a formulation for DR5-binding polypeptide, an ordinary artisan would be motivated to use the antibody formulation of Alder to create a stable and pharmaceutically acceptable antibody formulation so that the DR5-binding polypeptide can be used to treat cancer patients. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Further, regarding the specific concentrations for all of the components of the composition, these are art recognized variables and therefore, one would engage in routine optimization to obtain the desired result of a stable formulation for the composition, thus arriving at these specific concentrations as claimed. See MPEP 2144.05 (II). The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention because an ordinary artisan would have found it obvious to optimize the formulation through routine experimentation. An ordinary artisan would have been motivated to optimize the formulation to make the most stable and effective composition. MPEP 2144 sets forth Applicant’s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because the specification teaches effective embodiments of the claimed invention with 20-70 mg/ml DR5-binding polypeptide, 5.3-6.7 pH, 5-20 mM histidine HCl, 7-10% sucrose, 0.1-0.8% poloxamer 188, and 1-10mM methionine (para[0095-0099]; embodiment 11), which is evidence of noncriticality to the claimed invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 53, 54, 59-62, 66, and 70 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-25 of co-pending application No. 18/865854 in view of Alder et al. 2011 (WO2011012637A2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are drawn to a method of treating cancer using the DR5-binding polypeptide in a pharmaceutical composition, comprising SEQ ID NOs: 7, recited above.
The co-pending claims recite a DR5 agonist administered with an IAP antagonist to treat cancer, where the DR5 agonist has SEQ ID NO: 1-7, and specifies that the DR5 agonist can be administered separately from the IAP antagonist. Therefore, the co-pending claims are drawn to the DR5 agonist with SEQ ID NO: 7 being administered alone to treat cancer.
Instant SEQ ID NO: 7 has identical sequence to co-pending SEQ ID NO: 7. However, the co-pending claims do not explicitly teach the pharmaceutical formulation beyond the DR5-binding polypeptide.
Alder teaches an anti-HER2 antibody composition comprising 50 to 350 mg/ml anti-HER2 antibody, about 1 to 100 mM histidine/HCl, about 1 to 500 mM sucrose, 5 to 25 mM methionine, 0.01 to 0.1% polyethylene-polypropylene copolymer (specifically Poloxamer 188), with a pH ranging from 5.5 +/- 2 that can be administered to patients as a cancer treatment (page 4). Some formulations also include a lyophilized formulation formed by lyophilizing the pharmaceutical formulation (claim 18), and a pharmaceutical formulation formed by reconstituting the lyophilized formulation in water (page 11, line 29-33 to page 12, line 1-6).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention by formulating the antibody of patented claim 24 in the pharmaceutical composition of Alder. One with ordinary skill in the art would have found it obvious to combine the DR5-binding polypeptide with the antibody formulation of Alder to make the claimed composition because Alder teaches that the combination of ingredients creates a stable formulation for pharmaceutically active antibodies for therapeutic use and that this stable formulation can be both effectively lyophilized and reconstituted in water. As U.S. Patent No. 10308720B2 does not teach a formulation for DR5-binding polypeptide, an ordinary artisan would be motivated to use the antibody formulation of Alder to create a stable and pharmaceutically acceptable antibody formulation so that the DR5-binding polypeptide can be used to treat cancer patients. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Further, regarding the specific concentrations for all of the components of the composition, these are art recognized variables and therefore, one would engage in routine optimization to obtain the desired result of a stable formulation for the composition, thus arriving at these specific concentrations as claimed. See MPEP 2144.05 (II). The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention because an ordinary artisan would have found it obvious to optimize the formulation through routine experimentation. An ordinary artisan would have been motivated to optimize the formulation to make the most stable and effective composition. MPEP 2144 sets forth Applicant’s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because the specification teaches effective embodiments of the claimed invention with 20-70 mg/ml DR5-binding polypeptide, 5.3-6.7 pH, 5-20 mM histidine HCl, 7-10% sucrose, 0.1-0.8% poloxamer 188, and 1-10mM methionine (para[0095-0099]; embodiment 11), which is evidence of noncriticality to the claimed invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Advisory Information
This action is Non-Final.
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/JOSEPH D. CESARE/ Examiner, Art Unit 1675 /JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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