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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 2, 2026 has been entered.
Applicant's amendment and reply filed June 2, 2026 have been received and entered into the case. Claims 6 - 7 are canceled; claims 1, 8 - 16 and 48 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 1, 8 – 16 and 48 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 method for treating a chronic wound or ulcer, wherein a plasmin preparation is administered and "wherein Lys-plasmin constitutes more than 50%" and "Glu-plasmin is present in a lesser amount." This preparation is not described in the specification as originally filed. Applicant cites paragraph 0115 (of the published application) in support of the new limitations. However, this paragraph states "predominantly Lys-plasmin with minor amounts of Glu-plasmin" which is neither the same nor inherently supports the newly recited claim limitations. For example, the claimed phrase encompasses a preparation comprising 51% Lys-plasmin and 49% Glu-plasmin, which does not find support in the specification, particularly since the specification states "minor amounts" of Glu-plasmin.
This is a new matter rejection.
Claim Rejections - 35 USC § 102
Previous rejections under 35 U.S.C. 102a1 and 102a2 as being anticipated by Ny et al. (US 2003/0147879) are withdrawn due to the amendment requiring the administered composition to includes more than 50% Lys-plasmin and less than 50% Glu-plasmin.
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, 10 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Ny et al. (US 2003/0147879) in view of Zwaal (WO 2013/024074).
Regarding claim 1, Ny teaches a method for treating wounds in a patient (one in need thereof), the method comprising intravenous administration of effective amounts of plasmin (a fibrinogenase) (abstract, 0023 – 0024). Ny does not teach the method wherein the plasmin is a preparation of Lys-plasmin at more than 50% and Glu-plasmin is present in a lesser amount. However, Ny teaches the plasmin may include functionally active plasmin fragments and derivatives of plasmin, preferring more than one type to be administered (0032). At the time the claims were filed, the claimed fragments were known in the art as therapeutic equivalents that can be interchanged and substituted for one another and with a reasonable expectation for obtaining predictable results. In support, Zwaal teaches therapeutic plasmin variants and derivatives Glu-plasmin and Lys-plasmin as functional alternatives for each other (p.5, 9, 11). As such, at the time the claims were filed, it would have been obvious to use the claimed fragments/derivatives as the plasmin in the methods of Ny for the express direction thereby and since they were well known and used therapeutic equivalents. It would have been further obvious to optimize the amount of the plasmin since they are the recognized active, thus a result effective variable, and with a reasonable expectation for successfully treating wounds. This is supported by Ny which teaches dosages are administered in a therapeutically active amount, at dosages and for periods of time necessary to achieve the desired result, which may be adjusted for optimum therapeutic response (0061).
Regarding claim 10, the patient may have a diabetic ulcer or bed sores (pressure ulcer) (0022, 0023, 0029, 0054).
Regarding claim 15, Ny teaches the plasmin is administered as pharmaceutical in a pharmaceutical carrier (0024).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claims 1, 8 – 9, 10 – 15 and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Ny et al. (US 2003/0147879) as evidenced by Kazmi et al. (2012) in view of Zwaal (WO 2013/024074).
Regarding claim 1, Ny teaches a method for treating wounds in a patient (one in need thereof), the method comprising intravenous administration of effective amounts of plasmin (a fibrinogenase) (abstract, 0023 – 0024). Ny does not teach the method wherein the plasmin is a preparation of Lys-plasmin at more than 50% and Glu-plasmin is present in a lesser amount. However, Ny teaches the plasmin may include functionally active plasmin fragments and derivatives of plasmin, preferring more than one type to be administered (0032). At the time the claims were filed, the claimed fragments were known in the art as therapeutic equivalents that can be interchanged and substituted for one another and with a reasonable expectation for obtaining predictable results. In support, Zwaal teaches therapeutic plasmin variants and derivatives Glu-plasmin and Lys-plasmin as functional alternatives for each other (p.5, 9, 11). As such, at the time the claims were filed, it would have been obvious to use the claimed fragments/derivatives as the plasmin in the methods of Ny for the express direction thereby and since they were well known and used therapeutic equivalents. It would have been further obvious to optimize the amount of the plasmin since they are the recognized active, thus a result effective variable, and with a reasonable expectation for successfully treating wounds. This is supported by Ny which teaches dosages are administered in a therapeutically active amount, at dosages and for periods of time necessary to achieve the desired result, which may be adjusted for optimum therapeutic response (0061).
Regarding claims 8 – 9, Ny does not teach the method where in the patient’s plasma viscosity decreases as claimed. However, Ny teaches administering effective amounts that enhance wound healing and increase systemic levels of plasminogen 10, 50 or 100% more than prior to administration of the actives (0038). In this regard, increased levels of plasminogen (and plasmin) would inherently result in decreased plasma viscosity as it functions to break down fibrin (See Kazmi et al. for support). Moreover, at the time the claims were filed, it would have been obvious to one of ordinary skill in the art to optimize the amount of plasmin administered in the methods of Ny as a matter of routine experimentation and procedure, in order to obtain results effective to treat wounds and ulcers.
Regarding claim 10, the patient may have a diabetic ulcer or bed sores (pressure ulcer) (0022, 0023, 0029, 0054).
Regarding claims 11 – 14 and 48, Ny does not teach the method wherein administration dose and regimen is as claimed. However, Ny states that the plasmin may be formulated into pharmaceutical compositions for administration to subjects in an amount effective, at dosages and for periods of time necessary to achieve the desired result. Specifically, that a therapeutically active amount of a substance may vary according to factors such as the disease state, age, sex, and weight of the individual; dosage regimen may be adjusted to provide the optimum therapeutic response; and that more than one divided dose may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation (0061). Moreover, Ny specifically teaches one practicing the methods to optimize the therapeutic amount, dosage and dosage administrations when practicing the methods of treating wounds and ulcers.
Regarding claim 15, Ny teaches the plasmin is administered as pharmaceutical in a pharmaceutical carrier (0024).
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Claims 1, 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Ny et al. (US 2003/0147879) in view of Zwaal (WO 2013/024074) and further in view of Novokhatny et al. (2003).
Regarding claim 1, Ny teaches a method for treating wounds in a patient (one in need thereof), the method comprising intravenous administration of effective amounts of plasmin (a fibrinogenase) (abstract, 0023 – 0024). Ny does not teach the method wherein the plasmin is a preparation of Lys-plasmin at more than 50% and Glu-plasmin is present in a lesser amount. However, Ny teaches the plasmin may include functionally active plasmin fragments and derivatives of plasmin, preferring more than one type to be administered (0032). At the time the claims were filed, the claimed fragments were known in the art as therapeutic equivalents that can be interchanged and substituted for one another and with a reasonable expectation for obtaining predictable results. In support, Zwaal teaches therapeutic plasmin variants and derivatives Glu-plasmin and Lys-plasmin as functional alternatives for each other (p.5, 9, 11). As such, at the time the claims were filed, it would have been obvious to use the claimed fragments/derivatives as the plasmin in the methods of Ny for the express direction thereby and since they were well known and used therapeutic equivalents. It would have been further obvious to optimize the amount of the plasmin since they are the recognized active, thus a result effective variable, and with a reasonable expectation for successfully treating wounds. This is supported by Ny which teaches dosages are administered in a therapeutically active amount, at dosages and for periods of time necessary to achieve the desired result, which may be adjusted for optimum therapeutic response (0061).
Regarding claim 15, Ny teaches the plasmin is administered as pharmaceutical in a pharmaceutical carrier (0024).
Regarding claim 16, Ny does not teach the pharmaceutical composition having an acidic pH. However, Novokhatny teaches acidification of plasmin formulations remarkably stabilize the plasmin against auto-degradation, is equivalent to neutral pH formulations (abstract, p. 1037 right col.) and exhibits efficacy for long term activity in vivo (p.1037 right col). At the time the claims were filed, one of ordinary skill in the art would have been motivated to acidify the compositions of Ny for the advantages of long term stability and efficacy in vivo, as disclosed by Novokhatny, and with a reasonable expectation for successfully treating wounds and ulcers.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues that Ny refers to a broad class of "plasmin" and fails to teach more than 50% of Lys-plasmin with Glu-plasmin in a lesser amount and the secondary references fail to remedy this deficiency. Specifically, that Zwaal and Novokhatny do not teach Lys-plasmin at more than 50% or administering intravenously for chronic wounds or ulcers; but only that various homologs were known in the art and formulation stability, respectively. Finally, applicant argues that the various truncated forms are not equivalent as shown by applicant's data.
However, these arguments fail to persuade.
Initially, regarding applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
As it pertains to Ny, the reference specifically teaches that “plasmin” includes functionally active plasmin fragments wherein a plasmin composition may contain more than one type, derivative, or homolog of plasmin (0032). It is noted that applicant’s own specification construes “plasmin” to include wild type, functional mutants, functional fragments and combinations thereof (paragraph 0058 of the published application), revealing an equivalence in scope and teachings. As evidenced by Zwaal, Lys-plasmin and Glu-plasmin were well known examples of these fragments, and would have been immediately recognized as an effective plasmin to one of ordinary skill in the art. Further, since the plasmin is a recognized active, or result effective variable, it would have been obvious to one practicing the method obtained by the combined teachings to optimize the amount as a matter of routine practice and because Ny specifically teaches one to do so (0061).
Regarding secondary references, it is maintained that Ny teaches administering intravenous plasmin and the secondary references are relied upon to demonstrate increased levels of plasminogen and plasmin inherently result in decrease plasma viscosity; that the claimed plasmin fragments were known equivalents in the art; and acidifying plasmin formulations was known to stabilize the plasmin. Since applicant fails to rebut these points, they are considered points of agreement.
Regarding applicant’s argument that the various truncated forms are not equivalent as shown by applicant's data, while the data may reflect a variance in effectiveness, this alone is insufficient to demonstrate what is known in the art and acknowledged by applicant. That is, that plasmin and its functional fragments and derivatives were well known in the art to perform as substitutes for each one another to obtain predictable results, particularly tied to treating wounds and ulcers (see Ny 0032; Zwaal pages 5, 9, 11; applicant’s specification at paragraphs 0058 – 0072).
Thus, absent evidence of an unexpected result, the invention as a whole is prima facie obvious over the references.
No claims are allowed.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/RUTH A DAVIS/ Primary Examiner, Art Unit 1699
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