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 .
Amendments
Claim 1 has been amended to now recite a method for treating multiple sclerosis comprising administering to a subject a therapeutically effective amount of plasminogen.
Claims 2-5 have been canceled.
Claims 11 and 14 have been amended to replace “compound” with plasminogen in order to conform with the amendment to claim 1.
Claim 12 has been amended to remove the parenthetical language.
Claims 1 and 6-14 are currently pending and have been examined on their merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/06/2025 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Drawings
Previous objection to the drawings
The drawings were previously objected to because the partial figures presented in Figures 1-9 were not labeled properly. Applicant has made the appropriate correction and the objection to the drawings is therefore withdrawn.
Claim Objections
Previous objection to the claims
Claim 1 was objected to for minor informalities. Claim 1 has been amended such that the objection is moot.
Claim 4 has been canceled, rendering the objection moot.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112:
(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.
(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.
Previous rejections under 35 U.S.C. § 112
RE: Rejection of claims 1-14 under 35 U.S.C. 112(a) because the specification, while being enabling for treating multiple sclerosis with some compounds does not reasonably provide enablement for preventing and treating multiple sclerosis with every compound covered by the scope of the claim.
Claims 1-14 were previously rejected for scope of enablement. Claim 1 has been amended to be limited to a method for treatment by administration of plasminogen.
Accordingly, because the claim has been amended such that the scope is limited only to treatment of multiple sclerosis with plasminogen, the rejection is withdrawn.
RE: Rejection of claims 1-4 and 11-14 under 35 U.S.C. 112(a) as failing to comply with the written description requirement.
Claims 1-14 were previously rejected as failing to comply with the written description requirement. Because the claim has been amended such that the scope is limited only to treatment of multiple sclerosis with plasminogen, the rejection is withdrawn.
RE: Rejection of claims 2-3 and 12 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor, regards as the invention.
Claims 2-3 and 12 were previously rejected as being indefinite. Claims 2-3 are canceled, rendering their rejection moot. Applicant has amended claim 12 to remove the parenthetical language. According, the rejection of claim 12 is withdrawn.
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 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.
Previous rejection under 35 U.S.C. § 102(a)(1) and 102(a)(2)
Claims 1-2, 4, and 14 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Stringer et al. (US 6,497,877 B1).
Claims 1-2, 4, and 14 were rejected as being anticipated by Stringer et al., which teaches methods for treating multiple sclerosis by administering a plasminogen activator or derivative thereof. Because applicant has amended claim 1 such that the administered composition is not a plasminogen activator, the rejection under 35 U.S.C. § 102 has been withdrawn.
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.
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.
Previous rejections under 35 U.S.C. § 103
Claim 1 has been amended such that the administered composition is limited to plasminogen. Applicant argues that the amended claims overcome the prior art for the following reasons.
First, applicant asserts that nothing in Stringer, Goldenberg, or Li alone or in combination would have led a person of ordinary skill in the art to the subject matter of the amended claims. Specifically, applicant asserts that Goldenberg does not teach or suggest administering plasminogen to treat multiple sclerosis and Li is directed towards methods of repairing diabetic nerve injury, which has distinct etiology from multiple sclerosis.
Second, applicant asserts that the examples in the specification demonstrate that plasminogen is effective in treating multiple sclerosis by promoting myelin sheath regeneration, promoting the expression of neurofilament protein, and promoting an increase in myelin basic protein levels in the corpus callosum.
Applicant’s arguments have been fully considered but are not sufficient to overcome the teachings of the prior art.
With respect to the first argument, as discussed in the rejection of record, Goldenberg teaches that multiple sclerosis is a chronic autoimmune, inflammatory neurological disease and goals of multiple sclerosis therapies include providing symptomatic relief, which is aimed at maintaining function and improving quality of life (p. 175, left col., par. 1 and p. 176, left col., par. 4-5). Therefore, because Li teaches that plasminogen can treat neuroinflammation, it would have been obvious to have used plasminogen for the treatment of multiple sclerosis. And although Stringer is directed to treating multiple sclerosis with a “plasminogen activator”, that does not mean that Stringer does not suggest the use of plasminogen per se. To the contrary, a person having ordinary skill in the art would have recognized plasminogen to be a suitable composition for treatment of multiple sclerosis because Stringer’s methods chiefly concern activating plasminogen. Nonetheless, the prior art provides sufficient motivation to make such a modification because 1) Li directly teaches the capability of plasminogen to treat a specific symptom which is shared between the two conditions (neuroinflammation) and 2) Goldenberg teaches that the goals of multiple sclerosis therapies involve providing symptomatic relief.
With respect to the second argument, although it is accepted that applicant may have characterized how administration of plasminogen elicits changes in vivo, there is no requirement that the prior art provided these teachings because these are merely scientific explanations for how the plasminogen elicits its effects. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999)(MPEP § 2112(I)). As discussed above, it was previously known that plasminogen could be administered to treat neuroinflammation and it was also previously known that activation of the plasminogen pathway could treat multiple sclerosis. Accordingly, it is obvious to have arrived at a method of treating multiple sclerosis by administering plasminogen.
For at least these reasons, the amended claims are obvious over the prior art. In the interest of being fully responsive to applicant’s amendments, the rejections of record are withdrawn and new grounds of rejection are set forth below.
New grounds of rejection under 35 U.S.C. § 103
Claims 1 and 6-14 are rejected under 35 U.S.C. 103 as being unpatentable over Stringer et al. (US 6,497,877 B1) in view of Goldenberg (Pharmacy and Therapeutics, 2012, vol. 37(3), pages 175-184) and Li et al. (US 2018/0369345 A1; cited in IDS filed on 07/27/2023).
Regarding claim 1, Stringer teaches a method of treating an organism (i.e., a subject) afflicted by an inflammatory disease (col. 2, lines 64-65). Stringer teaches that inflammatory diseases include diseases such as multiple sclerosis (col. 9, lines 50-64). Accordingly, Stringer teaches a method for treating multiple sclerosis.
With respect to the method comprising administration of plasminogen, although Stringer teaches administration of plasminogen activators, it does not teach the administration of plasminogen per se.
Nonetheless, Li et al. (hereinafter Li) teaches methods for preventing or repairing diabetic nerve injury (e.g., nerve tissue injury or neuroinflammation) comprising administering a therapeutically effective amount of plasminogen or plasmin to a subject ([0010]-[0011]). Li teaches that plasmin is a key component of the plasminogen activation system and plasmin is formed by the proteolysis of plasminogen by plasminogen activators ([0005]). Finally, Li teaches that plasminogen has significant effects in nerve repair ([0009]).
Goldenberg reviews multiple sclerosis and teaches that multiple sclerosis is a chronic autoimmune, inflammatory neurological disease and goals of multiple sclerosis therapies include providing symptomatic relief, which is aimed at maintaining function and improving quality of life (p. 175, left col., par. 1 and p. 176, left col., par. 4-5).
Accordingly, because Stringer teaches the treatment of multiple sclerosis by administering a component of the plasminogen activation pathway (plasminogen activator) and because Li teaches that nerve tissue injury and neuroinflammation can be treated by administering plasminogen as “plasminogen has significant effects in nerve repair” ([0009]), it would have been obvious to have modified Stringer’s method such that Stringer’s plasminogen activator is substituted with plasminogen. There would have been a reasonable expectation of success when making this modification because Goldenberg teaches neuroinflammation to be a symptom of multiple sclerosis and Li teaches that plasminogen can be used to treat neuroinflammation. This obviousness is based upon the “Simple Substitution of One Known Element for Another to Obtain Predictable Results” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
With respect to the composition being administered to a subject in a therapeutically effective amount, Stringer teaches that the compounds of the invention will contain an effective amount of the plasminogen activator or derivative thereof in order to prepare pharmaceutically acceptable compositions suitable for administration to a human or animal (col. 8, lines 30-37). More specifically, Stringer teaches administration of a therapeutically effective amount of the composition (claim 1). Additionally, Li teaches that plasminogen is administered in a therapeutically effective amount to a subject ([0010]). As such, it would have been obvious to have administered a therapeutically effective amount of plasminogen in the modified method.
Thus, claim 1 is obvious over Stringer in view of Li and Goldenberg.
Regarding claim 6, as discussed above, Stringer in view of Li and Goldenberg makes obvious the administration of plasminogen for the purpose of treating multiple sclerosis.
Li teaches that the plasminogen can be one which has at least 80% sequence identity with SEQ ID NO: 2 ([0036]). Applicant’s SEQ ID NO: 2 has 100% identity with Li’s SEQ ID NO: 2 (see attached “Sequence Comparison.pdf”). Thus, Li’s range (“at least 80%”) overlaps with the instantly claimed range (“at least 75%”). Because the sequences are identical, it is considered that Li’s composition has the proteolytic activity of plasminogen. This interpretation is supported by the fact that Li describes a human natural plasminogen and it therefore must have the activity of plasminogen ([0030]).
Regarding claim 7, as discussed above, Li teaches the same composition and therefore it must have the same activity (i.e., the lysine binding activity of plasminogen). This interpretation is supported by the fact that Li describes a human natural plasminogen and it therefore must have the activity of plasminogen ([0030]).
Regarding claim 8, Li teaches that the plasminogen of the present invention comprises a protein containing a plasminogen active fragment and still having plasminogen activity (i.e., the proteolytic activity of plasminogen)([0053]). Li defines this fragment as SEQ ID NO: 14 or an amino acid sequence having an amino acid sequence identity of at least 80% with SEQ ID NO: 14. Applicant’s SEQ ID NO: 14 has 100% identity with Li’s SEQ ID NO: 14 (see previously attached “Sequence Comparison.pdf”). Thus, Li’s range (“at least 80%”) overlaps with the instantly claimed range (“at least 75%”).
Regarding claim 9, as discussed above, Li envisions variants of SEQ ID NO: 2 such as those having at least 80% identity to SEQ ID NO: 2. Li teaches that the variant can be a conservatively substituted variant ([0020]).
Regarding claim 10, Li teaches that the plasminogen can be human natural plasminogen ([0020]). As discussed above, Li teaches variants of this natural plasminogen, which are considered to be synthetic human plasminogen.
Regarding claims 11-13, as discussed above, Stringer in view of Goldenberg and Li renders obvious the method of treating multiple sclerosis by administering plasminogen.
And although Stringer does not teach that the compound is used in combination with one or more other therapeutic methods or medicaments, Goldenberg reviews the therapeutic regimens typically employed in the treatment of multiple sclerosis and teaches that there are eight FDA-approved therapeutic agents to reduce disease activity and progression in patients with MS (p. 176, left col., par. 5). Among these are beta interferons, glatiramer acetate, mitoxantrone, natalizumab, and fingolimod (p. 176, Table 1). Goldenberg teaches that laquinimod, teriflunomide, BG-12, daclizumab, alemtuzumab, rituximab, and ocrelizumab may be potential medications for multiple sclerosis (p. 179, Table 2) and teaches the off-label use of azathioprine, methotrexate, and cyclophosphamide, mycophenolate mofetil, and cladribine (p. 179, left col., par. 1 through right col., par. 2). Finally, Goldenberg teaches that “a combination of drugs, and physical, speech, and occupational therapies” may relieve symptoms and promote a satisfactory quality of life (p. 183, left col., par. 1).
Since Stringer in view of Goldenberg and Li renders obvious the administration of plasminogen to treat multiple sclerosis and Goldenberg teaches a litany of therapeutic options which may be combined to relive symptoms and promote a satisfactory quality of life, it would have been obvious to have further modified the method of Stringer such that it involves the administration of one or more other therapeutic methods or medicaments (claim 11) such as physical therapy (claim 12) or an immunosuppressant (claim 13) such as azathioprine or methotrexate (p. 178, right col., par. 9 through p. 179, left col., par. 1). There would have been a reasonable expectation of success because Goldenberg teaches therapies as combinable and the modification would have been expected to more effectively treat the symptoms of multiple sclerosis. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Thus, claims 11-13 are obvious over Stringer in view of Goldenberg and Li.
Regarding claim 14, Stringer teaches administration of the composition through oral, topical, inhalation, or parental administration routes (claims 4-7). Stringer gives specific examples such as intravascular infusion (i.e., intravenous administration or intraarterial administration)(col. 9, lines 7-9), aerosol inhalation (col. 9, lines 17-19).
Li teaches that plasminogen can be administered intranasally (i.e., through nasal inhalation), through aerosol, intravenously, intraperitoneally, subcutaneously, intracranially, intrathecally, intraarterially, and intramuscularly ([0079]).
As such, it would have been obvious to have administered plasminogen through one of the routes listed above.
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.
Previous double patenting rejections
RE: Rejection of claims 1-2 and 4-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,400,142 B2 in view of Goldenberg (Pharmacy and Therapeutics, 2012, vol. 37(3), pages 175-184).
Applicant argues that the claims, as amended, overcome the nonstatutory double patenting rejection over claims 1-20 of ‘142 in view of Goldenberg. Specifically, applicant argues that diabetic nerve injury is predominantly in the peripheral nerves and multiple sclerosis is a central nervous system disease having a different mechanism from those caused by diabetic nerve injuries. Thus, one of ordinary skill in the art would allegedly not have been led to the subject matter of the amended claims with a reasonable expectation of success.
Applicant’s argument has been fully considered but is not sufficient to overcome the rejection of record. As discussed in the rejection of record, ‘142 teaches the administration of an effective amount of plasminogen including by treating nerve injury including neuroinflammation or nerve tissue damage. Thus, because the method of ‘142 is for treating the injured nerve (i.e., is not directed to treating diabetes), a person having ordinary skill in the art would have recognized that if plasminogen is useful for repairing “nerve tissue injury or neuroinflammation”, it would be reasonably expected to be able to treat the neuroinflammatory component of multiple sclerosis.
For at least this reason, the teachings of Goldenberg are directly applicable to the ‘142 patent and the instant claims must be rejected for nonstatutory double patenting over ‘142 in view of Goldenberg. The rejection of record has been maintained but modified in order to address the amendments to the claims.
RE: Rejection of claims 1-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,400,142 B2 in view of Goldenberg (Pharmacy and Therapeutics, 2012, vol. 37(3), pages 175-184) and Pelisch et al. (PLOS ONE, 2015, vol. 10(4), pages 1-17; cited in IDS filed on 07/27/2023).
As discussed above, the rejection over ‘142 in view of Goldenberg has been maintained. The instant rejection (i.e., the use of Pelisch) was made in order to address the administration of an antagonist of fibrinolysis inhibitor. Because claim 3 is canceled, the rejection of record is withdrawn.
RE: Provisional rejection of claims 1-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 17/793,371 in view of Shaw et al. (Journal of Neuroscience, 2017, vol. 37(14), pages 3776-3788; cited in IDS filed on 07/27/2023) and Goldenberg (Pharmacy and Therapeutics, 2012, vol. 37(3), pages 175-184).
Applicant has requested abeyance on this provisional rejection. As the application is not in condition for allowance and the provisional rejection cannot be held in abeyance, the provisional rejection must be maintained but has been modified in order to address the new amendments to the claims.
RE: Provisional rejection of claims 1-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/037,299.
Applicant has requested abeyance on this provisional rejection. As the application is not in condition for allowance and the provisional rejection cannot be held in abeyance, the provisional rejection must be maintained but has been modified in order to address the new amendments to the claims.
RE: Provisional rejection of claims 1-14 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/037,300.
Applicant has requested abeyance on this provisional rejection. As the application is not in condition for allowance and the provisional rejection cannot be held in abeyance, the provisional rejection must be maintained but has been modified in order to address the new amendments to the claims.
Maintained but modified double patenting rejections
Claims 1 and 6-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,400,142 B2 in view of Goldenberg (Pharmacy and Therapeutics, 2012, vol. 37(3), pages 175-184).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Regarding claim 1, claims 1 and 5 of ‘142 are directed to methods of repairing diabetic nerve injury comprising administering an effective amount of plasminogen. Although the claims of ‘142 do not teach that the method is for treating multiple sclerosis, claim 18 of ‘142 teaches that the nerve injury is neuroinflammation or nerve tissue injury.
Goldenberg reviews multiple sclerosis and teaches that multiple sclerosis is a chronic autoimmune, inflammatory neurological disease and goals of multiple sclerosis therapies include providing symptomatic relief, which is aimed at maintaining function and improving quality of life (p. 175, left col., par. 1 and p. 176, left col., par. 4-5).
Since the claims of ‘142 teach that plasminogen is suitable for the treatment of nerve tissue injury and neuroinflammation and Goldenberg teaches that multiple sclerosis is a chronic neuroinflammatory disease, it would have been obvious to have modified the method of ‘142 such that it was instead directed to treating multiple sclerosis. There would have been a reasonable expectation of success because the etiology of multiple sclerosis (neuroinflammation) is the mechanism of treatment of the methods of ‘142. This obviousness is based upon the “Some Teaching, Suggestion, or Motivation in the Prior Art That Would Have Led One of Ordinary Skill To Modify the Prior Art Reference or To Combine Prior Art Reference Teachings To Arrive at the Claimed Invention” rationale set forth in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007). See MPEP 2143(I)(G).
Regarding claims 6-8, the claims of ‘142 encompass administration of plasminogen having at least 80% sequence identity with SEQ ID NO: 2 (claims 4 and 16-17). As discussed above in the rejection under 35 U.S.C. § 103 (applied to the pre-grant publication of this patent), applicant’s SEQ ID NO: 2 is 100% identical to the prior art SEQ ID NO: 2.
Regarding claim 9, although the claims of ‘142 do not directly teach a “conservative substitution”, a person having ordinary skill in the art would be prompted to experiment with various “variants” of SEQ ID NO: 2 and would have arrived at a plasminogen having a conservative substitution with a reasonable expectation of success.
Regarding claim 10, SEQ ID NO: 2 is the natural human plasminogen (see the sequence listing for SEQ ID NO: 2 in col. 37-38 of the ‘142 patent).
Regarding claims 11-13, claims 1 and 5 of ‘142 teach that the method further comprises additional therapy such as physical therapy or drugs including neurotrophic drugs, anti-infective drugs (e.g., antibiotics or antivirals).
Regarding claim 14, claim 2 of ‘142 teaches intravenous administration.
Claims 1 and 6-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-10, and 12-17 of copending Application No. 17/793,371 in view of Shaw et al. (Journal of Neuroscience, 2017, vol. 37(14), pages 3776-3788; cited in IDS filed on 07/27/2023) and Goldenberg (Pharmacy and Therapeutics, 2012, vol. 37(3), pages 175-184).
Although the claims at issue are not identical, they are not patentably distinct for the following reasons.
Regarding claim 1, claim 1 of ‘371 is directed to a method for treating nerve injury comprising administering to a subject a therapeutically effective amount of plasminogen.
Copending claim 1 differs because it is not directed to a method of treating multiple sclerosis.
Nevertheless, Shaw teaches that multiple sclerosis is a chronic demyelinating disease of the central nervous system characterized by autoreactive CD4+ T cells causing microglial- and macrophage-mediated destruction and phagocytosis of the myelin sheath (p. 3776, left col., par. 1 through right col., par. 2). Additionally, fibrin is “the premier” proteolytic target of plasmin, has been documented in demyelinating plaques of MS patients, and fibrin matrices appear to drive microglial and macrophage migration, leading to demyelination and loss of motor function (p. 3784, left col., par. 3 through right col., par. 1).
Accordingly, because the copending application is directed to a method for treating nerve injury, such as by promoting the repair of damaged nerve (claim 4) or regeneration of the myelin sheath (claim 5), it would have been obvious to have modified the method of treating nerve injury such that the method is instead for treating multiple sclerosis because (i) it was known that myelin sheath damage is the causative factor for multiple sclerosis and (ii) it was known that the fibrinolytic pathway could alleviate demyelination.
Regarding claims 6-8, claims 12-14 of ‘371 limit the plasminogen to one having at least 75% similarity to the natural plasminogen sequence (SEQ ID NO: 2) or the active fragment (SEQ ID NO: 14).
Regarding claim 9, claim 13 of ‘371 teaches that the variant is a conservative substitution variant.
Regarding claim 10, claim 15 of ‘371 teaches that the plasminogen is natural or synthetic human plasminogen.
Regarding claims 11-13, as discussed above, it would have been obvious to have arrived at a method of treating multiple sclerosis. The copending claims do not teach that the compound is administered in combination with one or more other therapeutic method or medicaments.
Goldenberg reviews the therapeutic regimens typically employed in the treatment of multiple sclerosis and teaches that there are eight FDA-approved therapeutic agents to reduce disease activity and progression in patients with MS (p. 176, left col., par. 5). Among these are beta interferons, glatiramer acetate, mitoxantrone, natalizumab, and fingolimod (p. 176, Table 1). Goldenberg teaches that laquinimod, teriflunomide, BG-12, daclizumab, alemtuzumab, rituximab, and ocrelizumab may be potential medications for multiple sclerosis (p. 179, Table 2) and teaches the off-label use of azathioprine, methotrexate, and cyclophosphamide, mycophenolate mofetil, and cladribine (p. 179, left col., par. 1 through right col., par. 2). Finally, Goldenberg teaches that “a combination of drugs, and physical, speech, and occupational therapies” may relieve symptoms and promote a satisfactory quality of life (p. 183, left col., par. 1).
Since ‘372 in view of Shaw makes obvious the use of the components recited in claim 1 to treat multiple sclerosis, it would have been obvious to have further modified the method such that it further involves the administration of one or more other therapeutic methods or medicaments (claim 11) such as physical therapy (claim 12) or an immunosuppressant (claim 13) such as azathioprine or methotrexate (p. 178, right col., par. 9 through p. 179, left col., par. 1). There would have been a reasonable expectation of success because Goldenberg teaches therapies as combinable and the modification would have been expected to more effectively treat the symptoms of multiple sclerosis.
Regarding claim 14, although the copending claims do not teach any particular route of administration, it would have been obvious to have experimented with various administration routes to arrive at the most efficacious routes, such as those recited in the instant claim. There would have been a reasonable expectation of success because this claim is not particularly limited and encompasses dozens of potential routes of administration.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 6-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/037,299.
Although the claims at issue are not identical, they are not patentably distinct for the following reasons.
Regarding claim 1, claim 1 of ‘299 is directed to a method for promoting the formation of mature BDNF and/or increasing BDNF levels comprising administering to a subject a therapeutically effective amount of a plasminogen pathway activator. Claim 15 of ‘299 limits the activator to plasminogen.
Although copending claim 1 is not directed to a method of treating multiple sclerosis, claim 6 of ‘299 defines the method as being used in subjected having neuronal injuries from multiple sclerosis and instant claim 4 recites the increase in the level of BDNF. Moreover, claim 7 of ‘299 is for “preventing or treating a BDNF-associated disease or condition”, which can be multiple sclerosis (see claim 8). Accordingly, these claims encompass overlapping subject matter.
Regarding claims 6-8, claims 16-17 of ‘299 limit the plasminogen to one having at least 80% similarity to the natural plasminogen sequence (SEQ ID NO: 2) or the active fragment (SEQ ID NO: 14).
Regarding claim 9, claim 18 of ‘299 teaches that the plasminogen can be a “variant” of plasminogen. Paragraphs [0052]-[0053] of the specification of ‘299 defines “variant” as including proteins obtained by substitution of 1-100 conservative amino acids.
Regarding claim 10, as discussed above, SEQ ID NO: 2 is the natural synthetic human plasminogen.
Regarding claims 11-13, claim 10 of ‘299 teaches the use of one or more other drugs or therapies.
Regarding claim 14, claim 11 of ‘299 teaches intravenous, intramuscular, intrathecal, nasal, aerosol, nasal drop, or eye drop administration routes.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 6-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 16-18 of copending Application No. 18/037,300.
Although the claims at issue are not identical, they are not patentably distinct for the following reasons.
Regarding claim 1, claim 1 of ‘300 is directed to a method for promoting the formation of mature NGF and/or increasing NGF levels comprising administering to a subject a therapeutically effective amount of a plasminogen pathway activator. Claim 15 of ‘300 limits the activator to plasminogen.
Although copending claim 1 is not directed to a method of treating multiple sclerosis, claim 6 of ‘300 defines the method as being used in subjected having neuronal injuries from multiple sclerosis and instant claim 4 recites the increase in the level of NGF. Moreover, claim 7 of ‘300 is for “preventing or treating an NGF-associated disease or condition”, which can be multiple sclerosis (see claim 8). Accordingly, these claims encompass overlapping subject matter.
Regarding claims 6-8, claims 16-17 of ‘300 limit the plasminogen to one having at least 80% similarity to the natural plasminogen sequence (SEQ ID NO: 2) or the active fragment (SEQ ID NO: 14).
Regarding claim 9, claim 18 of ‘300 teaches that the plasminogen can be a “variant” of plasminogen. Page 23 of the specification of ‘300 defines “variant” as including proteins obtained by substitution of 1-100 conservative amino acids.
Regarding claim 10, as discussed above, SEQ ID NO: 2 is the natural human plasminogen.
Regarding claims 11-13, claim 10 of ‘300 teaches the use of one or more other drugs or therapies.
Regarding claim 14, claim 11 of ‘300 teaches intravenous, intramuscular, intrathecal, nasal, aerosol, nasal drop, or eye drop administration routes.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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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/GRANT C CURRENS/Examiner, Art Unit 1651
/MICHELLE F. PAGUIO FRISING/Primary Examiner, Art Unit 1651