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 .
Election/Restrictions
Claims 9, 11-13, and 19-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/05/2026.
Applicant elected Group I, drawn to pharmaceutical formulations of anti-PD-1. Within Group I, applicant elected the following species:
Species 1: pembrolizumab comprising SEQ ID NOs: 1-8
Species 2: sucrose as a stabilizer
Species 3: surfactant-free for surfactant
Species 4: histidine for buffer
Claim Status
Claims 4-5 are cancelled. Claims 9, 11-13, and 19-22 are withdrawn. Claims 1-3, 6-8, 10, and 14-18 are pending in the instant application and currently under consideration for patentability under 37 CFR 1.104.
Priority
Applicant' s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The instant application is a 371 of International PCT/KR2021/001210 filed on 01/29/2021 and claims benefit under 35 U.S.C. 119(a)-(d) to foreign application KR10-2020-0011353 filed on 01/30/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant cannot rely upon the certified copy of the foreign priority application because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Because an English translation of the certified copy of the foreign priority application has not been made of the record, the examiner cannot establish whether or not what is claimed in the instant application was properly disclosed in the foreign priority application. Therefore, the benefit to the foreign priority application date is not granted.
Claims 1-3, 6-8, 10, and 14-18 have the effective filing date of 01/29/2021, corresponding to PCT/KR2021/001210.
Information Disclosure Statement
The information disclosure statements filed on 07/29/2022 and 02/27/2024 have been considered. Signed copies are enclosed.
Notably, the disclosure statements filed list Search Reports. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because it contains “the present disclosure relates to”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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 1-3, 6-8, 10, and 14-18are 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.
The term “about” in claims 1, 3, 10, and 15-18 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The use of “about” renders the pH of the pharmaceutical formulation (claim 1), concentration of pembrolizumab (claims 3 and 16-18), concentration of sucrose (claims 10 and 16), and concentration of histidine (claim 15-16) indefinite.
The specification states “numerical values described herein are considered to include the meaning of ‘about’, unless otherwise specified” (¶ 0008). However, pH values and concentrations of pembrolizumab, sucrose, and histidine provided are prefaced with the caveat that they “may be” those numerical values (¶ 0008, “pH of the pharmaceutical formulation may be…”; ¶ 0017, “concentration of the anti-PD-1 antibody, for example, a pembrolizumab, or an antigen binding fragment thereof, may be…”; ¶ 0019, “concentration of the sugar may be…”; ¶ 0029, “concentration of the buffer may be…”). Therefore, the term “about” is still indefinite despite the given definition as a person having ordinary skill in the art would not understand the metes and bounds of the claims and the rejection still applies.
For the purposes of claim interpretation, “about” will be considered as ±10% the given numerical value and/or range.
Claims 2, 6-8, and 14 are included in this rejection as they depend and/or incorporate claim 1.
Claim 2 recites the limitation "a pembrolizumab" in the last line. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 6-8, 10, and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Application No. US-20180339045-A1) in view of Sharma et al. (Application No. US-20200147213-A1).
Instant Application SEQ ID NO
Sharma et al. SEQ ID NO
1
6
2
7
3
8
4
1
5
2
6
3
7
10
8
5
Claim 1
With regard to claim 1, Li et al. teach an anti-PD-1 antibody pharmaceutical preparation comprising a histidine buffer (Pg. 4, ¶ 0056, “[p]referred pharmaceutically acceptable buffers include, but are not limited to, histidine-buffers”), a sucrose stabilizer (Pg. 2, ¶ 0017, “at least one stabilizer in a pharmaceutical” such as “sucrose”), and a pH between 4.5-6.0 (Pg. 2, ¶ 0018, “the pH of the formulation may range [from] 4.5 to 6.0”) that “optionally can further comprise a surfactant” (Abstract) in some embodiments, indicating a surfactant is not necessary for a stable pharmaceutical preparation.
Li et al. do not teach that the anti-PD-1 antibody is pembrolizumab with SEQ ID NOs: 1-8.
Sharma et al. teach a pharmaceutical formulation of anti-PD-1 antibody, specifically pembrolizumab, with SEQ ID NOs: 1-8 from the instant application (see above table for how sequences correspond; SEQ ID NOs: 1-3, 5, 6-8, and 10; Pg. 10-11, Table 2, ”Pembrolizumab Light Chain” and ”Pembrolizumab Heavy Chain”). SEQ ID NO: 7 from the instant application, defined as the variable region of the heavy chain of pembrolizumab, is encompassed by SEQ ID NO: 10 from Sharma et al., defined as the heavy chain of pembrolizumab. A variable region of a heavy chain exists by definition within a heavy chain of an antibody. All other listed sequences from Sharma et al. are exact matches.
Sharma et al. further teach in some embodiments that sucrose is a stabilizer and histidine is a buffer (Pg. 1, ¶ 0010, “sucrose” and “histidine buffer”) and a pH of 5.0 (Pg. 13, ¶ 0166, “the buffer has a pH of about 5.0” and “buffers that will control the pH in this range include… histidine”).
Sharma et al. do not teach a formulation that does not comprise a surfactant.
Anti-PD-1, specifically pembrolizumab, pharmaceutical formulations were known and used prior to the effective filing date of the application. The simple substitution of one known element for another (i.e. anti-PD-1 antibody for pembrolizumab) would be expected to obtain predictable results with a reasonable expectation of success (see MPEP 2141[III][B]). Here, use of pembrolizumab is an established and well-performing treatment for cancer (Sharma et al., Pg. 8, ¶ 0115), giving motivation for its use. Substitution of anti-PD-1 antibody for pembrolizumab is reasonable as pembrolizumab is a species of the genus anti-PD-1, having the same binding partner.
It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the application to substitute anti-PD-1 antibodies for pembrolizumab in a pharmaceutical formulation as taught in Li et al., wherein a surfactant is optional.
Claims 2-3
With regard to claims 2-3, Sharma et al. further teach the anti-PD-1 antibody is pembrolizumab (Pg. 2, ¶ 0018, “[i]n specific embodiments of the invention the anti-PD-1 antibody is pembrolizumab,” applicable to claim 2), wherein the concentration in some embodiments is about 25 mg/mL (Pg. 11, ¶ 0138, “the API [i.e. the anti-PD-1 antibody or antigen binding fragment thereof] is present in a concentration of about… 25 mg/mL,” applicable to claim 3).
Claims 6-8 and 10
With regard to claims 6-8 and 10, Sharma et al. further teach the stabilizer is a polyol, specifically sucrose, wherein the concentration in some embodiments is about 6% to about 8% w/v (Pg. 1, ¶ 0010, “about 6% to about 8% w/v sucrose”).
Claims 14-15
With regard to claims 14-15, Sharma et al. further teach histidine as a buffer, wherein the concentration in some embodiments is about 5 mM to less than about 20 mM (Pg. 1, ¶ 0010, “about 5 mM to about 20 mM histidine buffer”).
Claim 16
With regard to claim 16, Sharma et al. further teach:
the anti-PD-1 antibody is pembrolizumab (Pg. 2, ¶ 0018, “[i]n specific embodiments of the invention the anti-PD-1 antibody is pembrolizumab”), wherein the concentration in some embodiments is about 25 mg/mL (Pg. 11, ¶ 0138, “the API [i.e. the anti-PD-1 antibody or antigen binding fragment thereof] is present in a concentration of about… 25 mg/mL”);
the stabilizer is sucrose, wherein the concentration in some embodiments is about 6% to about 8% w/v (Pg. 1, ¶ 0010, “about 6% to about 8% w/v sucrose”), and;
the buffer is histidine, wherein the concentration in some embodiments is about 5 mM to less than about 20 mM (Pg. 1, ¶ 0010, “about 5 mM to about 20 mM histidine buffer”).
Claims 17-18
With regard to claims 17-18, Sharma et al. further teach in some embodiments that pembrolizumab has concentrations of about 25 mg/mL or about 150 mg/mL. (Pg. 11, ¶ 0138, “the API [i.e. the anti-PD-1 antibody or antigen binding fragment thereof] is present in a concentration of about… 25 mg/mL” or “about 150 mg/mL”).
Accordingly. Li et al. in view of Sharma et al. make obvious the instant claims 1-3, 6-8, 10, and 14-18.
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 1-3, 6-8, 10, and 14-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-7, 9, 11-13, and 20 of copending Application No. 17/784,251 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 1 of teaches a pharmaceutical formulation comprising:
an anti-PD-1 antibody,
a stabilizer,
a pH of about 4.5 to about 6.5, and
a buffer.
whereas
Claims 1 and 11 of Pat. ‘251 teach a pharmaceutical formulation comprising:
an anti-PD-1 antibody,
a stabilizer,
a pH of about 4.5 to about 6.5, and
does not include a buffer.
Instant claim 1 differs from claims 1 and 11 of Pat. ‘251. as it includes histidine as a buffer.
Pat. ‘251 states in its specification that “[t]he phrase ‘the pharmaceutical formulation not comprising an ingredient A’, as used herein may mean that the pharmaceutical formulation does not, or substantially not comprise, the ingredient A. The phrase ‘substantially not comprise an ingredient A’ may be interpreted to encompass a case where the ingredient A is not present at all, a case where the ingredient A is present in a trace amount, if any, so as not to substantially affect features of the pharmaceutical formulation, or a case where the ingredient A is present in an undetectable amount” (¶ 0027, emphasis added).
This definition allows for an undetermined amount of buffer to be present in the composition of claims 1 and 11 of Pat. ‘251. Therefore, instant claim 1 anticipates claims 1 and 11 of Pat. ‘251.
Instant claims 2-3, 6-8, 10, and 14-18 further teach a pharmaceutical formulation comprising:
an anti-PD-1 antibody, specifically pembrolizumab (claim 2), with a concentration of about 5 mg/mL to about 300 mg/mL (claim 3) OR about 5 mg/mL to about 200 mg/mL (claim 17)
sucrose as a stabilizer (claims 6-8) with a concentration of about 1.0% to about 15.0% w/v (claim 10);
does not comprise a surfactant (claims 14-18)
whereas
Claims 3-7, 9, 12-13, and 20 of Pat. ‘251 further teach a pharmaceutical formulation comprising:
an anti-PD-1 antibody, specifically pembrolizumab, with a concentration of about 5 mg/mL to about 200 mg/mL (claims 3-5);
a polyol, specifically sucrose, as a stabilizer with a concentration of about 1.0% to about 15.0% w/v (claims 6-7 and 9);
does not comprise a surfactant (claim 12-13, 20)
There is no difference in scope between instant claims 1-3, 6-8, 10, and 14-18 and claims 1, 3-7, 9, 11-13, and 20 of Pat. ‘251.
Consequently, the instant claims 1-3, 6-8, 10, and 14-18 are anticipated by claims 1, 3-7, 9, 11-13, and 20 of Pat. ‘251.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-3, 6-8, 10, and 14-18 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jessica M Priest whose telephone number is (571)272-8469. The examiner can normally be reached Mon-Fri 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.M.P./Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642