DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on February 19 and March 19, 2026 have been entered.
Claim 53 is canceled; claims 23 – 27, 30 – 52 and 54 are pending and have been considered on the merits. All arguments have been fully considered.
Claim Rejections - 35 USC § 112
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 23 – 27, 30 – 52 and 54 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.
The claims are drawn to a formulation of ADAMTS13 comprising 0.5 – 5% sugar and/or sugar alcohol and 100 – 200 mM of a pharmaceutically acceptable salt having a pH between 6.5 and 9.0, that is stable for at least 24 hours at 4°C, such that the ADAMTS13 activity measured before and after a 24 hour period are substantially the same. The specification as originally filed fails to describe a composition comprising ADAMTS13, sugar and salt that exhibits the claimed stability parameters. Instead, the specification discloses a formulation stabile for the claimed period of time and temperature includes ADAMTS13 and a buffer containing histidine and NaCl (example 7 and figure 14). This is a new matter rejection.
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.
Previous rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph are withdrawn due to removing trademark names and replacing with their respective chemical names; clarifying dependency; cancelation of claim 53 and clarification of product characteristics in claim 54.
Claims 23 – 27, 30 – 52 and 54 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 23 and its dependents are drawn to a formulation of ADAMTS13, however the claims fail to recite any amount or inclusion of ADAMTS13. Clarification is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claims 23, 25 – 27, 30 – 32, 36 – 41, 43, 46 – 50, 52 and 54 are rejected under pre-AIA 35 U.S.C. 102b and 102e as being anticipated by Ginsburg et al. (US 2006/0233784, IDS filed 11.19.2024, USPAP #3) as evidenced by “Hank’s Salts” (Wikipedia entry).
Regarding claims 23, 30 – 31, 40, 48 and 50, Ginsburg teaches aqueous formulations comprising ADAMTS13 in combination with stabilizing compounds and pharmaceutical carriers (0303), wherein the carriers include 2% sucrose, 2% mannitol (0315, 0319) and buffered saline such as Hank’s solution or physiologically buffered saline (e.g., a buffer comprising 0.1465M or 146.5mM salts to maintain physiological pH of about 7.0 – 7.4, See Wikipedia “Hank’s Salts” and “pH,” p.5) (0309). Since the buffered saline is intended to maintain physiological pH, the formulation is interpreted to have a pH of 7.0 – 7.4, which falls within the claimed range. Although Ginsburg does not teach the formulation is stable for at least 24 hours at 4°C such that the ADAMTS13 activity is substantially the same before and after the storage period, the compositions taught by Ginsburg are the same as that claimed. In this regard, the compositions must inherently exhibit the same result when stored at the same temperature and time period.
Regarding claims 25 – 27, 49, Hank’s salt solution includes sodium chloride, potassium chloride, calcium chloride and magnesium chloride, and about 1mM calcium which falls within the claimed range (see Wikipedia “Hank’s Salts”).
Regarding claim 32, the compositions may further include vehicles such as fatty oils, acid esters, ethyl oleate or triglycerides (non ionic surfactants) (0314).
Regarding claim 36 – 39, Ginsburg teaches the formulations may further include 1 – 50 mM histidine (a buffer).
Regarding claim 41, Ginsburg teaches the concentration of ADAMTS13 is from 0.1 to 100,000 micrograms, up to a total dose of about 1 g, depending upon the route of administration (0323), or about 0.01mg/mL or higher.
Regarding claims 43 and 46 – 47, Ginsburg teaches the formulations are administered for treating thrombocytopenic purpura, stroke and heart attack (myocardial infarction) (0009 – 0010, 0019, 0134, 0307).
Regarding claim 54, although Ginsburg does not teach the claimed intended result of the formulation, Ginsburg does teach that the formulations are stabile during storage and retain activity levels (0292). Moreover, since the compositions are the same, the intended results must also occur in the formulation of the prior art.
The reference anticipates the claimed subject matter.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 23 – 24, 32 – 36, 43 – 45 and 51 – 52 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Ginsburg et al. (US 2006/0233784, IDS filed 11.19.2024, USPAP #3) as evidenced by “Hank’s Salts” (Wikipedia entry).
Regarding claim 23, Ginsburg teaches aqueous formulations comprising ADAMTS13 in combination with stabilizing compounds and pharmaceutical carriers (0303), wherein the carriers include 2% sucrose, 2% mannitol (0315, 0319) and buffered saline such as Hank’s solution or physiologically buffered saline (e.g., a buffer comprising 0.1465M or 146.5mM salts to maintain physiological pH of about 7.0 – 7.4, See Wikipedia “Hank’s Salts” and “pH,” p.5) (0309). Since the buffered saline is intended to maintain physiological pH, the formulation is interpreted to have a pH of 7.0 – 7.4, which falls within the claimed range. Although Ginsburg does not teach the formulation is stable for at least 24 hours at 4°C such that the ADAMTS13 activity is substantially the same before and after the storage period, the compositions taught by Ginsburg are the same as that claimed. In this regard, the compositions must inherently exhibit the same result when stored at the same temperature and time period.
Regarding claim 24, Ginsburg does not teach the composition comprising the claimed activity of ADAMTS13. However, since the ADAMTS13 is identified as the active component, it is considered a result effective variable. Thus, it would have been obvious to one of ordinary skill in the art to optimize the amount of salt in the solutions of Ginsburg as a matter of routine practice and experimentation and with a reasonable expectation for successfully obtaining an effective ADAMTS13 formulation.
Regarding claims 32 and 33, the compositions may further include vehicles such as fatty oils, acid esters, ethyl oleate or triglycerides (non ionic surfactants) (0314). Although the reference does not teach the claimed amount of surfactant, it would have been obvious to one of ordinary skill in the art to optimize the amount of surfactants in the solutions of Ginsburg as a matter of routine practice and experimentation and with a reasonable expectation for successfully obtaining an effective ADAMTS13 formulation.
Regarding claims 34, 35 and 51, Ginsburg does not teach the formulation further comprising Polysorbate 80. However, Ginsburg teaches stabilizers are included in the compositions (0314). At the time the claims were filed, Polysorbate 80 was a well known and commonly used stabilizer in the art. In support, applicant’s specification states “Pharmaceutically acceptable nonionic surfactants that may be used in the formulations of the present invention are known in the art of pharmaceutical science, and include, without limitation, Polysorbate 80(Tween 80)…” Thus, at the time the claims were filed, it would have been obvious to one of ordinary skill in the art to include the instant components as a buffer in the formulation of Ginsburg as a matter of common practice.
Regarding claims 43 – 45, Ginsburg teaches the formulations are administered for treating thrombocytopenic purpura (TTP) (0009 – 0010, 0019, 0134, 0307). Although treatment is not specified for hereditary or acquired, Ginsburg does teach the ADAMTS13 will help in treating familial and acquired forms of TTP (0151), suggesting that one in the art could expect to treat both types of TTP with a reasonable expectation for success. Thus, in following the teachings of Ginsburg, one of ordinary skill in the art would have been motivated to administer the composition to treat familial and acquired forms of TTP with a reasonable expectation for success.
Regarding claim 52 (and 36), Ginsburg teaches the formulations may further include 1 – 50 mM histidine (a buffer). Ginsburg does not teach the formulation further comprising both histidine and arginine. However, Ginsburg teaches physiological buffering agents can be used in the formulations (0309). At the time the claims were filed, mixtures of arginine and histidine were well known and commonly used buffers in the art. In support, applicant’s specification states “Pharmaceutically acceptable buffering agents are well known in the art, and include without limitation…histidine…arginine…and mixtures thereof.” Thus, at the time the claims were filed, it would have been obvious to one of ordinary skill in the art to include the instant components as a buffer in the formulation of Ginsburg as a matter of common practice.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claims 23 and 42 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Ginsburg et al. (US 2006/0233784, IDS filed 11.19.2024, USPAP #3) as evidenced by “Hank’s Salts” (Wikipedia entry); in view of Anderson et al. (2006, IDS filed 11.19.2024, NPL #2).
Regarding claim 23, Ginsburg teaches aqueous formulations comprising ADAMTS13 in combination with stabilizing compounds and pharmaceutical carriers (0303), wherein the carriers include 2% sucrose, 2% mannitol (0315, 0319) and buffered saline such as Hank’s solution or physiologically buffered saline (e.g., a buffer comprising 0.1465M or 146.5mM salts to maintain physiological pH of about 7.0 – 7.4, See Wikipedia “Hank’s Salts” and “pH,” p.5) (0309). Since the buffered saline is intended to maintain physiological pH, the formulation is interpreted to have a pH of 7.0 – 7.4, which falls within the claimed range. Although Ginsburg does not teach the formulation is stable for at least 24 hours at 4°C such that the ADAMTS13 activity is substantially the same before and after the storage period, the compositions taught by Ginsburg are the same as that claimed. In this regard, the compositions must inherently exhibit the same result when stored at the same temperature and time period.
Regarding claim 42, Ginsburg does not teach the compositions further including zinc in the claimed amounts. However, Anderson teaches ADAMTS13 including zinc in ADAMTS13 formulations results in enhanced ADAMTS13 activity by 3 and 2-fold, respectively, while 6 fold when added with calcium (abstract). In this regard, at the time the claims were filed, one of ordinary skill in the art would have been motivated by Anderson to include calcium and/or zinc in the formulations of Ginsburg for the disclosed effects of enhancing ADAMTS13 activity at synergistic levels.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
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 23 – 27, 30 – 52 and 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims
1 – 50 of U.S. Patent No. 8623352;
1 – 27 of U.S. Patent No. 9351935;
1 – 19, 24 – 46, 51 – 54 of U.S. Patent No. 9572778;
1 – 15, 23 – 30 of U.S. Patent No. 9937244;
1 – 16, 23 – 28 of U.S. Patent No. 10238720;
1 – 15, 23 – 28 of U.S. Patent No. 10758599;
1 – 15, 23 – 26 of U.S. Patent No. 11564979; and
1 – 13, 17, 19 – 20 of U.S. Patent No. 12178861.
Although the claims at issue are not identical, they are not patentably distinct from each other because each of the claim sets are drawn to the same varied formulations of ADAMTS13 and method for treating the same conditions of TTP, stroke and/or myocardial infarction.
Response to Arguments
Applicant argues that the amended claims recite a stability limitation wherein Ginsburg does not teach the claimed formulation; that Ginsburg does not teach the claimed ingredients, amounts or pH as claimed and therefore cannot inherently exhibit the claimed stability features; that Ginsburg teaches adding a buffer to lyophilized ADAMTS13 powder prior to use, not an aqueous formulation that remains stable for at least 24 hours at 4°C; and that that Ginsburg does not inherently teach the claimed composition since the reference fails to teach any aqueous formulation.
Regarding the argument that Ginsburg does not teach the claimed stability limitation, these limitations do not further define the claimed composition but instead recite an intended use of the composition (e.g., storage conditions, testing conditions) that do not materially change the claimed composition itself. Moreover, the stability limitations are recited as a result of the claimed combination of ADAMTS13, 0.5 – 5% sugar/sugar alcohol and 100 – 200 mM pharmaceutical salt with a pH of 6.5 – 9.0, which are disclosed by Ginsburg.
Regarding the argument that Ginsburg does not teach the claimed ingredients, amounts or pH and can therefore not inherently exhibit the claimed stability features, it is reiterated that Ginsburg expressly teaches preparations comprising ADAMTS13, 2% sucrose and physiological buffer such as Hank’s (0309, 0319) which includes the claimed amount of salts and pH. In this regard, it is maintained that the reference teaches the composition claimed by applicant and also the compositions disclosed in the specification, which are lyophilized compositions of ADAMTS13, buffer, sucrose, polysorbate and histidine that is reconstituted in water or buffer (examples, figures, 0319).
Regarding the argument that Ginsburg teaches adding a buffer to lyophilized ADAMTS13 powder prior to use, not an aqueous formulation that remains stable for at least 24 hours at 4°C, it is reiterated that adding a buffer to lyophilized ADAMTS13 is also what applicant discloses in the specification. Thus, the teachings of the prior art and applicant’s disclosure are comparable in scope. Regarding the claimed composition, it is maintained that the composition is disclosed by Ginsburg even if reconstituting from a lyophilized ADAMTS13 as the claims do not exclude any compositions made from previously lyophilized components or require any other additional components. As such, the composition disclosed by Ginsburg would inherently exhibit the claimed stability features.
Regarding the argument that Ginsburg does not inherently teach the claimed composition since the reference fails to teach any aqueous formulation, Ginsburg clearly and repeatedly teaches aqueous compositions (0127, 0309, 0314, 0319).
Thus, the arguments fail to persuade.
Applicant argues that Ginsburg is not enabled for the claimed composition; is sufficiently generic to result in extensive trial and error to arrive at the claimed invention; and places undue experimentation to obtain an aqueous solution of ADAMTS13 well beyond routine experimentation.
Initially, it is maintained that Ginsburg teaches and suggests the claimed components in the claimed amounts, which is 2% sucrose (sugar) mixed with Hank’s buffer solution (0319, 0309) as discussed in the rejection above. In this regard, no routine experimentation is required by one practicing the invention of Ginsburg to combine ADAMTS13 sucrose and buffer (aqueous formulation). Notwithstanding, including buffers in a pharmaceutical composition of ADAMTS13 does not rise to the level of extensive trial and error processes or undue experimentation. MPEP 3164.01 states “A patent need not teach, and preferably omits, what is well known in the art.” In this regard, Ginsburg is not required to teach all well known and used buffers that might be used in the compositions. Despite this directive, Ginsburg expressly teaches various and specific buffers that might be included, e.g., Hank’s solution (0309), which is more specific than applicant’s recitation of a generic “sodium phosphate buffer.” As such, it is maintained that Ginsburg clearly teaches and enables the claimed aqueous solution.
Regarding applicant’s argument that the specification is “sufficiently generic” to aqueous solutions, it should be noted that the instant specification recites “aqueous” exactly 3 times. In addition, all disclosures of a formulation “reconstituted with sterile water” is in the context of reconstituting a lyophilized formulation of ADAMTS13, sucrose, polysorbate and buffer (figures, examples). In fact, the only disclosure of a formulation stabile for the claimed period of time and temperature includes ADAMTS13 and a buffer containing histidine and NaCl (example 7 and figure 14), which is also “sufficiently generic” and not commensurate in scope with the claimed invention. Moreover, the teachings of the prior art are comparable to those of the instant application.
Applicant argues that since claim 53 was not previously rejected under 35 U.S.C. 103(a), incorporation of the limitations to claim 23 renders the rejection moot.
However, as the limitations of claim 53 were and are rejected under 102 and no other arguments are presented, the claims remain rejected for the reasons of record.
Applicant acknowledges the obvious double patenting rejections and requests they be held in abeyance.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUTH A DAVIS whose telephone number is (571)272-0915. The examiner can normally be reached Monday - Friday (8am - 4pm).
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RUTH A DAVIS/ Primary Examiner, Art Unit 1699
Prosecution Insights