DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-32 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on February 4, 2026 is acknowledged. Applicant’s election without traverse of the species, adalimumab is acknowledged. Claims 11-20 and 28-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-10, 21-27 and 32 are under examination.
Claim Objections
Claim 32 is objected to because they depend on a non-elected claim. For purposes of this Office Action, the limitations of claim 1 are included for the examination of claim 32. However, this treatment does not relieve applicant the burden of responding to this objection.
Claim Rejections - 35 USC § 112
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.
Claim 1-10, 21-27 and 32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites a pharmaceutical composition comprising methotrexate or a pharmaceutically acceptable salt, hydrate or derivative thereof. Claims 1-10, 21-27 and 32 are indefinite for reciting “derivative” in claim 1because the exact meaning of the term is not clear. The term “derivative” is not one, which has a universally accepted meaning in the art nor is it one which has been adequately defined in the specification. The primary deficiency in the use of this phrase is the absence of an ascertainable meaning for said phrase. Since it is unclear how the methotrexate is derivatized to yield the class of methotrexate derivatives referred to in the claims, there is no way for a person of skill in the art to ascribe a discrete and identifiable class of compounds to said phrase. In addition, since the term “derivative” does not appear to be clearly defined in the specification, and the term can encompass many compounds which are only slightly related to methotrexate. In the absence of a single defined art recognized meaning for the phrase and lacking a definition of the term “derivative” in the specification, one of skill in the art could not determine the metes and bounds of the claims.
Claim 32 recites a kit comprising a first injection device having a fluid reservoir containing the methotrexate or the pharmaceutically acceptable salt, hydrate or derivative thereof, and a second injection device separate from the first injection device" having a fluid reservoir containing the pharmaceutically active biopharmaceutical.
However, claim 1 which it ultimately depends from recites a pharmaceutical composition comprising methotrexate and at least one pharmaceutically active biopharmaceutical which is at least partially dissolved in the solvent in combination with the methotrexate. It is not clear how a single pharmaceutical composition comprising methotrexate and a pharmaceutically active biopharmaceutical can be present in the two injection devices.
Claim Rejections - 35 USC § 102
(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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 6-9, 21-23, 25-27 and 32 is/are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Dave et al (US 2013/0058930, March 7, 2013, IDS).
The claims are drawn to a pharmaceutical composition comprising methotrexate or a pharmaceutically acceptable salt, hydrate or derivative thereof, and at least one pharmaceutically active biopharmaceutical which is at least partially dissolved in the solvent in combination with the methotrexate or the pharmaceutically acceptable salt, hydrate or derivative thereof.
Dave disclose a pharmaceutical composition comprising a combination of methotrexate and infliximab (paragraph 76). Dave disclose injectable solutions comprising 20 mg methotrexate per 0.4 ml (50 mg/ml) (paragraphs 120, 121). Dave disclose an injection device for subcutaneous or intramuscular administration of a medicament comprising methotrexate (paragraphs 74-87). Dave discloses methods of treating autoimmune and inflammatory disorders with methotrexate and infliximab (paragraphs 2, 11-15, 76, claim 25).
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim(s) 1-10, 21-26 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dave et al (US 2013/0058930, March 7, 2013, IDS, cited previously) in view of Lazar et al (2017/0252437, published September 7, 2017, IDS).
Dave does not disclose that the biopharmaceutical is adalimumab.
Lazar discloses pharmaceutical compositions of adalimumab at 1-150 mg/ml (paragraph 25). Lazar disclose that the pharmaceutical adalimumab formulation is designed for subcutaneous administration for use in the treatment of an autoimmune
disorder (paragraph 26).
One of ordinary skill in the art would have been motivated to apply Lazar’s biopharmaceutical, adalimumab with Dave’s pharmaceutical composition comprising methotrexate because both adalimumab and methotrexate are used to treat autoimmune and inflammatory disorders. The court has held that it is obvious to combine two compositions, in order to form a third composition, when each of the two compositions is taught by the prior art to be useful for the same purpose. (In re Kerkhoven, 626, F.2s 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to combine Dave’s pharmaceutical composition comprising methotrexate with Lazar’s biopharmaceutical, adalimumab because the prior art teaches that both are useful for the treatment of autoimmune and inflammatory disorders. It would have been prima facie obvious to substitute Lazar’s biopharmaceutical, adalimumab for Dave’s pharmaceutical composition comprising infliximab because both infliximab and adalimumab are anti-TNF antibodies that have been shown to treat autoimmune and inflammatory disorders.
Claim(s) 1-10, 21-27 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Dave et al (US 2013/0058930, March 7, 2013, IDS, cited previously) in view of Lazar et al (2017/0252437, published September 7, 2017, IDS, cited previously) in further view of Murphy et al (US 2020/0164087, published May 28, 2020, IDS).
Neither Dave nor Lazar disclose a drug-loaded nanoparticle or microparticle comprising the pharmaceutical composition comprising methotrexate and an active pharmaceutical.
Murphy disclose mineral coated microparticles for sustained delivery of biologically active molecules (paragraphs 9-14). Murphy discloses that suitable biologically active molecules include adalimumab and infliximab (paragraph 111).
One of ordinary skill in the art would have been motivated to apply Murphy’s mineral coated microparticles to Dave and Lazar’s pharmaceutical composition comprising methotrexate and adalimumab because Murphy discloses suitable active agents include infliximab, adalimumab and methotrexate (paragraphs 9-16, 51, 87) and recites that the microparticle would provide sustained delivery and/or local delivery of biologically active molecules and could be used to treat autoimmune and inflammatory disease (Id). It would have been prima facie obvious to combine Dave and Lazar’s pharmaceutical composition comprising methotrexate and adalimumab with Murphy’s mineral coated microparticles comprising adalimumab and methotrexate to have a drug-loaded microparticle comprising methotrexate and adalimumab.
Claims 1, 4-10, 21-26 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (US 2023/0312700, published October 5, 2023, effective filing date June 19, 2019).
Jones disclose a pharmaceutical composition comprising a combination of methotrexate and adalimumab (paragraphs 67-77, 86, 89). Jones disclose that adalimumab is present in the formulation at a concentration of 100 mg/mL (paragraph 74, 2725). Jones disclose an injection device and vial for subcutaneous administration of a medicament comprising adalimumab (paragraphs 89, 321, 3248, 1665-1669, 1949-2008, 2725).
Claims 1-10, 21-26 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (US 2023/0312700, published October 5, 2023, effective filing date June 19, 2019, cited previously) in view of Dave et al (US 2013/0058930, March 7, 2013, IDS, cited previously) and Meyers et al (US 2021/0213201, published July 15, 2021, effective filing date August 7, 2020).
Jones does not specifically disclose methotrexate at a concentration of 5 milligrams per milliliter to 25 milligrams per milliliter or at a concentration of from 25 milligrams per milliliter to 50 milligrams or two injection devices.
Dave disclose injectable solutions comprising 20 mg methotrexate per 0.4 ml (50 mg/ml) (paragraphs 120, 121).
Myers disclose injectable solutions comprising methotrexate and adalimumab (paragraphs 9, 54, 241-254). Myers disclose that the medical injector may comprise one or two containers that can include either the same medicament or two different medicaments paragraphs.
One of ordinary skill in the art would have been motivated to apply Dave’s methotrexate concentrations and Myers’s dual container devices to Jones’s injection device comprising a pharmaceutical composition comprising a combination of methotrexate and adalimumab because Jone, Dave and Myers all disclose injection devices comprising methotrexate and an anti-TNF antibody. It would have been prima facie obvious to combine Jones’s injection device comprising a pharmaceutical composition comprising a combination of methotrexate and adalimumab with Dave’s methotrexate concentrations and Myers’s dual container devices to have an injection device for subcutaneous administration comprising a fluid reservoir containing a pharmaceutical composition comprising methotrexate at a concentration of 5 milligrams per milliliter to 50 milligrams per milliliter and adalimumab at a concentration of 20 milligrams per milliliter to 100 milligrams per milliliter.
Claims 1-10, 21-27 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (US 2023/0312700, published October 5, 2023, effective filing date June 19, 2019, cited previously) in view of Dave et al (US 2013/0058930, March 7, 2013, IDS, cited previously) and Meyers et al (US 2021/0213201, published July 15, 2021, effective filing date August 7, 2020, cited previously) in further view of Murphy et al (US 2020/0164087, published May 28, 2020, IDS, cited previously).
Neither Jones, Dave nor Myers disclose a drug-loaded nanoparticle or microparticle comprising the pharmaceutical composition comprising methotrexate and an active pharmaceutical.
Murphy disclose mineral coated microparticles for sustained delivery of biologically active molecules (paragraphs 9-14). Murphy discloses that suitable biologically active molecules include adalimumab and infliximab (paragraph 111).
One of ordinary skill in the art would have been motivated to apply Murphy’s mineral coated microparticles to Jones, Dave and Myers injection device comprising a pharmaceutical composition comprising methotrexate and adalimumab because Murphy discloses suitable active agents include infliximab, adalimumab and methotrexate (paragraphs 9-16, 51, 87) and recites that the microparticle would provide sustained delivery and/or local delivery of biologically active molecules and could be used to treat autoimmune and inflammatory disease (Id). It would have been prima facie obvious to combine Jones, Dave and Myers injection device comprising a pharmaceutical composition comprising methotrexate and adalimumab with Murphy’s mineral coated microparticles comprising adalimumab and methotrexate to have a drug-loaded microparticle comprising methotrexate and adalimumab.
Summary
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark Halvorson whose telephone number is (571) 272-6539. The examiner can normally be reached on Monday through Friday from 9:00 am to 6:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Gregory Emch, can be reached at (571) 272-8149. The fax phone number for this Art Unit is (571) 273-8300.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARK HALVORSON/ Primary Examiner, Art Unit 1646
Prosecution Insights