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
Claims 1-14 are pending and under examination.
Information Disclosure Statement
The information disclosure statements filed 06/13/2023, 06/26/2024, 12/12/2024, and 04/02/2025 fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. The references for which no legible copies have been supplied are marked with a strike through the reference.
Claim Objections
Claim 2 is objected to because of the following informalities: Line 4 states “said osmolality regulator is selected from sodium chloride” and Line 7 states “said surfactant is selected from polysorbate 80”. The phrase “selected from” should be deleted as it is followed by a single excipient and not a list of excipients from which to select.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 12 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because the claims are not directed toward a: (1) composition of matter; (2) machine; (3) manufacture; or (4) process, but rather the “use” of a formulation comprising a recombinant anti-PD-1 monoclonal antibody, wherein no active method steps are present to suggest a process is being claimed. "Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101 MPEP 2173.05(q).
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 1-2, 7-8, 10, and 12-13 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.
Regarding claims 1-2, 7-8, 10, and 12-13, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 12, the meets and bound of the claims are indefinite. MPEP 2173.05(q) states attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness. Recitation of a use without any active, positive steps delimiting how this use is actually practiced is indefinite.
Claim Rejections - 35 USC § 112(d)
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.
Claims 9 and 11 are 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.
Claim 9 states "the formulation of claim 7, which is a monoclonal antibody", however, claim 9 is ultimately dependent on claim 1, which discloses the formulation comprises anti-PD-1 monoclonal antibody. Therefore, claim 9 does not further limit the subject matter of the claims upon which it depends.
Claim 11 discloses the formulation according to claim 1 is in the form of an aqueous formulation or lyophilized form. Claim 11 is dependent on claim 1, which discloses the formulation excipients as concentrations in solution (i.e. a buffer of 10-50 mM). Therefore, the formulation cannot be lyophilized and claim 11 fails to include all the limitations of claim 1.
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.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 5-10 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
The teachings of the specification and the claimed invention
The instant invention is directed to a stable formulation comprising a recombinant anti-PD-1 monoclonal antibody. Claim 5 defines the sequences of the CDRs of the anti-PD-1 antibody, claim 6 defines the heavy and light chain variable regions, and claim 7 defines the light chain constant region and heavy chain constant region.
The specification teaches two antibody clones: (1) mouse antibody PD1-M944 with 6 CDRs set forth in claim 5 and (2) human antibody PD1-H944 with 6 CDRs set forth in claim 5, heavy and light variable regions set forth in claim 6, and heavy and light constant regions set forth in claim 7.
Importantly, both of these antibodies at a minimum require all 6 CDRs that define both heavy and light chain variable regions.
The state of the prior art
It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro et. al., Front. Immunol. 2018; 8:1751 (see Section “The IgG Molecule” in paragraph 1 and Figure 1). While affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody (page 3 “The IgG Molecule, second and third paragraphs), those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori. E.g., id., (page 6 ending paragraph onto page 7).
The prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. For example, the unpredictability of single amino acid changes in an antibody is underscored by Winkler (J Immunol. 2000 Oct 15;165(8):4505-14) who teaches that a single amino acid change in a CDR can result in unpredictable and substantial changes in antibody specificity; see entire document (e.g., the abstract).
Similarly, Herold et al. (Sci Rep. 2017 Sep 25;7(1):12276) performed single- and double-point mutations in exemplary antibodies and found that a single point mutation in the VH CDR region can completely abolish antigen binding (Page 8, Paragraph 1, Line 11).
In all, the art shows that in order to define an antibody requires the identification of all 6 CDRs that define the binding regions of both heavy and light chain variable regions.
Claim analysis
In light of the teachings of the specification and the state of the relevant art, the claims have the following written description issues:
Claim 5 states: “wherein said recombinant anti-PD-1 monoclonal antibody comprises a light chain variable region and/or a heavy chain variable region”, thus not requiring all 6 CDRs and incompletely defining the binding region of the antibody.
Claim 6 claims the light chain variable region and the heavy chain variable regions in the alternative (line 4, “and/or”) thus also not requiring all 6 CDRs and incompletely defining the binding region of the antibody.
Because these claims do not require all 6 CDRs of the heavy and light chain binding domains, one of skill in the art would neither expect nor predict the appropriate functioning of the antibodies as broadly as is claimed. There is no disclosure of a correlation between structure and function that would allow those of skill in the art to recognize other members of the claimed genus from the disclosure.
That is, the specification provides neither a representative number of the encompassed antibodies, nor does it provide a descriptive of structural features that are common to the encompassed antibodies.
Since the disclosure fails to describe the common attributes or characteristics that identify members of the genus, and because the genus is highly variant, the artisan cannot envision the detailed structure of the encompassed antibodies and non-antibody proteins and therefore Applicant was not in possession of the instant claimed invention.
Claims 7-10 are also rejected under 35 USC § 112(a) for being dependent on claim 5 and not providing limitations that overcome the written description rejection.
Claim Rejections - 35 USC § 102
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.
Claims 1-3 and 11-14 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Sharma (US2020/0147213A1, published 05/14/2020, effectively filed 05/02/2017).
The disclosure of Sharma is directed to stable formulations of antibodies against PD-1 (see Abstract). Sharma provides antibody formulations for concentrations of antibody 5mg/mL to 200mg/mL ([0006], Line 1-3).
Regarding claims 1-3, pertaining to a stable formulation comprising a recombinant anti-PD-1 monoclonal antibody, Sharma teaches the following formulation:
25 mg/mL to 200 mg/mL of an anti-human PD-1 antibody (Sharma claim 9)
The antibody of the formulation is pembrolizumab, a recombinant, humanized IgG4 monoclonal antibody (Sharma claim 38, [0115], Lines 1-3)
5 to 20mM histidine buffer (Sharma claim 9)
Reconstitution of the formulation in 0.09% sodium chloride (osmolality regulator), which is equivalent to 154mM ([0271], Line 19)
1% to 3% w/v L-arginine salt (stabilizer) such as L-arginine HCl [0014], equivalent to 47.5 to 142.4 mM of arginine hydrochloride (Sharma claim 10), and teaches formulations with L-arginine HCl ranging from 15 mM to 427 mM (Pg. 31, Table 15)
0.01% to 0.04% w/v polysorbate 80 (Sharma claim 9)
The pH of the formulation is between 5.0 and 6.0 (claim 3)
Regarding claim 11, wherein the formulation is in the form of an aqueous formulation or lyophilized form, Sharma teaches anti-PD-1 antibody formulation is a reconstituted solution from a lyophilized formulation (Sharma claim 28)
Regarding claims 12 and 13, pertaining to the intended use of the formulation as a medicament for the treatment of a tumor or cancer, Sharma discloses a method of treating cancer in a human patient in need comprising administering an effective amount of the anti-human PD-1 antibody formulation (Sharma claim 40).
Regarding claim 14, wherein the formulation can be stored stably for 42 months at 2 to 8°C and for at least 12 months at 25°C, this claim recites an intended property that flows from the recited formulation and is thus anticipated by Sharma who teaches all of the instant invention limitations.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-4 and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over by Sharma (US2020/0147213A1, published 05/14/2020, effectively filed 05/02/2017) as applied to claims 1-3 and 11-14 above, and further in view of Whitaker ( J Pharm Sci. 2017 Nov;106(11):3230-3241, cited in IDS 12/12/2024).
The disclosure of Sharma discloses stable formulations of antibodies against PD-1 (see Abstract). Sharma’s teachings are set forth in the 35 U.S.C. 102 rejection above. Sharma teaches reconstitution of the formulation in 0.09% sodium chloride (osmolality regulator), which is equivalent to 154 mM ([0271], Line 19)
Sharma does not teach the concentration of sodium chloride is 120 mM.
This deficiency is taught by Whitaker.
The disclosure of Whitaker is directed to a study of various pharmaceutical excipients screened for viscosity-reducing effects on two different monoclonal antibodies (Abstract, Lines 5-7).
Regarding claim 4, wherein the concentration of sodium chloride is 120 mM, Whitaker teaches a range of sodium chloride antibody formulations ranging from 100 mM to 1 M NaCl. Whitaker shows that multiple antibodies formulated with 100 mM, 500 mM and 1 M NaCl have a “preferred range” low viscosity (Fig. 1, formulations 7-9).
It would have been obvious to one having ordinary skill in the art to modify the formulation of Sharma by using 120 mM NaCl. One would have been motivated to do because Whitaker teaches a range of NaCl that includes 120 mM that is ideal for antibody pharmaceuticals. Doing so is obvious on the basis of overlapping, approaching, and similar ranges, amounts, and proportions (see MPEP 2144.05). There would be an expectation of success in using 120 mM in the formulation of Sharma because Sharma already teaches the use of a similar concentration (154 mM NaCl) and Whitaker provides evidence that the claimed 120 mM NaCl can help maintain low viscosity of antibody formulations.
Claims 1-3 and 5-14 are rejected under 35 U.S.C. 103 as being unpatentable over by Sharma (US2020/0147213A1, published 05/14/2020, effectively filed 05/02/2017) as applied to claims 1-3 and 11-14 above, and further in view of Xie (WO2020/125712A1, published 06/25/2020, effectively filed 12/21/2018, cited in IDS 06/13/2023).
The applied reference (WO2020/125712A1) has a common applicant (SinoCellTech Ltd.) and inventor (Sun, Chunyun) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The disclosure of Sharma discloses stable formulations of antibodies against PD-1 (see Abstract). Sharma’s teachings are set forth in the 35 U.S.C. 102 rejection above.
Sharma does not teach the antibody of the instant invention with sequences set forth in instant claims 5-7.
This deficiency is taught by Xie.
The disclosure of Xie is directed to a recombinant humanized antibody against PD-1, which can be used for tumor or cancer immunotherapy (Pg. 2, [0001].
Regarding claims 5-7, Xie discloses the antibody clone PD1-H944. The corresponding sequence identifiers are shown in the table below:
Instant
Xie Clone PD1-H944
Claim 5
VL CDRs
SEQ ID NOs: 1-3
VH CDRs
SEQ ID NOs: 4-6
VL CDRs
SEQ ID NOs: 10-12
VH CDRs
SEQ ID NOs: 13-15 (see Xie Table 1)
Claim 6
VL SEQ ID NO: 8
VH SEQ ID NO: 7
VL SEQ ID NO: 23
VH SEQ ID NO: 22 (see Xie Table 2)
Claim 7
Kappa light chain constant region
SEQ ID NO: 10
IgG4 heavy chain constant region
SEQ ID NO: 9
Kappa light chain constant region
SEQ ID NO: 25
IgG4 heavy chain constant region
SEQ ID NO: 24 (see Xie Table 2)
Regarding claim 8, wherein the antibody is an IgG antibody, Xie teaches SEQ ID NO:24 is the IgG4 heavy chain constant region.
Regarding claim 9, wherein antibody is a monoclonal antibody, Xie teaches the antibody is monoclonal (Pgs. 14-15, [0017].
Regarding claim 10, wherein the antibody binds PD-1 protein with an affinity in KD average of 20-200 pM, this feature flows from the claimed antibody structure and is anticipated by the identical structure disclosed by Xie. To this end, Xie teaches that the average KD of PD1-H944 is 68.4 pM (Pg. 89, [0168]).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to use the anti-PD-1 antibody of Xie in the anti-PD-1 antibody formulation of Sharma. One would have been motivated to do so because Sharma provides an optimized antibody formulation and Xie discloses a humanized anti-PD-1 antibody with proven PD-1 specificity. Modifying the reference of Sharma with the antibody of Xie constitutes substitution of one known element for another to obtain predictable results. There would be an expectation of success of using the antibody of Xie in the formulation of Sharma because the antibodies of Xie and Sharma are both IgG4 and thus highly similar structurally and readily interchangeable.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,275,790 in view of Sharma (US2020/0147213A1, published 05/14/2020, effectively filed 05/02/2017) and Whitaker ( J Pharm Sci. 2017 Nov;106(11):3230-3241, cited in IDS 12/12/2024).
Regarding instant claim 1, ‘790 teaches a pharmaceutical composition comprising the anti-PD-1 antibody of the instant invention.
Regarding instant claims 5-10, ‘790 discloses the anti-PD-1 antibody identical to the instant invention. The corresponding sequence identifiers are shown in the table below:
Instant
Pat. No. 12,275,790
Claim 5
VL CDRs
SEQ ID NOs: 1-3
VH CDRs
SEQ ID NOs: 4-6
VL CDRs
SEQ ID NOs: 10-12
VH CDRs
SEQ ID NOs: 13-15 (‘790 claim 1)
Claim 6
VL SEQ ID NO: 8
VH SEQ ID NO: 7
VL SEQ ID NO: 23
VH SEQ ID NO: 22 (‘790 claim 2)
Claim 7
Kappa light chain constant region
SEQ ID NO: 10
IgG4 heavy chain constant region
SEQ ID NO: 9
Kappa light chain constant region
SEQ ID NO: 25
IgG4 heavy chain constant region
SEQ ID NO: 24 (‘790 claim 3)
Patent ‘790 does not teach the specific antibody formulation of the instant invention with the disclosed excipients and concentrations.
These deficiencies are taught by Sharma and Whitaker.
Sharma:
The disclosure of Sharma is directed to stable formulations of antibodies against PD-1 (see Abstract). Sharma provides antibody formulations for concentrations of antibody 5mg/mL to 200mg/mL ([0006], Line 1-3).
Regarding instant claims 1-4, pertaining to a stable formulation comprising a recombinant anti-PD-1 monoclonal antibody, Sharma teaches the following formulation:
25 mg/mL to about 200 mg/mL of an anti-human PD-1 antibody (Sharma claim 9)
The antibody of the formulation is pembrolizumab, a recombinant, humanized IgG4 monoclonal antibody (Sharma claim 38, [0115], Lines 1-3)
5 to 20mM histidine buffer (Sharma claim 9)
Reconstitution of the formulation in 0.09% sodium chloride (osmolality regulator), which is equivalent to 154mM ([0271], Line 19)
1 to 3% w/v L-arginine salt (stabilizer) such as L-arginine HCl [0014], equivalent to 47.5 to 142 mM of arginine hydrochloride (Sharma claim 10)
0.01% to 0.04% w/v polysorbate 80 (Sharma claim 9)
The pH of the formulation is between 5.0 and 6.0 (claim 3)
Regarding instant claim 11, wherein the formulation is in the form of an aqueous formulation or lyophilized form, Sharma teaches anti-PD-1 antibody formulation is a reconstituted solution from a lyophilized formulation (Sharma claim 28)
Regarding instant claims 12 and 13, pertaining to the intended use of the formulation as a medicament for the treatment of a tumor or cancer, Sharma discloses a method of treating cancer in a human patient in need comprising administering an effective amount of the anti-human PD-1 antibody formulation (Sharma claim 40).
Regarding instant claim 14, wherein the formulation can be stored stably for 42 months at 2 to 8°C and for at least 12 months at 25°C, this claim recites an intended result of the formulation and is thus anticipated by Sharma who teaches all of the instant invention limitations.
Whitaker:
The disclosure of Whitaker is directed to a study of various pharmaceutical excipients screened for viscosity-reducing effects on two different monoclonal antibodies (Abstract, Lines 5-7).
Regarding instant claim 4, wherein the concentration of sodium chloride is 120 mM, Whitaker teaches a range of sodium chloride antibody formulations ranging from 100 mM to 1 M NaCl. Whitaker shows that two different antibodies formulated with 100 mM, 500 mM and 1 M NaCl have a “preferred range” low viscosity (Fig. 1, formulations 7-9).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to one having ordinary skill in the art at the time of filing to formulate the antibody of ‘970 with the antibody formulation of Sharma and NaCl concentration of Whitaker. One would have been motivated to do so because ‘970 teaches the antibody in a pharmaceutical composition, but does not teach the specific formulation. There would be an expectation of success in modifying the invention of ‘970 with the formulations of Sharma and Whitaker because Sharma provides an optimized formulation for an IgG4 anti-PD-1 antibody suited for use with the instant antibody and Whitaker provides evidence that the claimed 120 mM NaCl can help maintain low viscosity of antibody formulations.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROL ANN CHASE whose telephone number is (571)270-0934. The examiner can normally be reached Monday-Friday 9:00am-6:00pm.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646