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 . 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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 17 March, 2026 has been entered.
Election/Restrictions
Applicant elected plasminogen of SEQ ID 2 to treat a spinal cord nerve injury in the reply filed on 21 July, 2025.
Claims Status
Claims 1, 12-15, and 18-26 are pending.
Claims 25 and 26 are new.
Claims 13 and 14 have been withdrawn from consideration due to an election/restriction requirement.
Withdrawn Rejections
The provisional rejection of claims 1, 12, 15, and 18-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 12, and 13 of copending Application No. 18/037,299 (US 20240000903) (reference application) in view of Boussios et al (Anticanc. Res. (2018) 38 p4987-4997) is hereby withdrawn due to the abandonment of the competing application.
The provisional rejection of claims 1, 12, 15, and 18-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 15 of copending Application No. 17/802,280 (US 20230139956) (reference application) in view of Kalb et al (World Neurol. (2015) 84(2) p351-357) is hereby withdrawn due to the abandonment of the competing application.
Maintained/Modified Rejections
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.
Claim(s) 1, 12, 15, and 18-25 are rejected under 35 U.S.C. 103 as being unpatentable over Davies et al (J. Neurotrauma (2006) 23(3/4) p397-408) in view of Cooper et al (Neurobiol Dis. (2018) 116 p60-68).
Davies et al discuss decorin induction of plasminogen in acute spinal injuries (title). Plasmin, which is produced from plasminogen by plasminogen activators, has a number of effects that are expected to be beneficial to promoting recovery in an injured CNS, such as degradation of scar tissue (p398, 1st column, 3d paragraph, continues to 2nd column, 1st paragraph), degradation of axon growth inhibitors (p402, 1st column, 2nd paragraph), increased cell motility (p402, 2nd column, 2nd paragraph), induction of increased levels of growth factors (p403, 1st column, 1st paragraph), and decreased apoptosis of neurons (p403, 1st column, 2nd paragraph). Note that plasmin itself is rapidly inactivated in the blood (p403, 2nd column, 3d paragraph), making it a poor choice as a therapeutic.
The difference between this reference and the examined claims is that this reference uses human decorin to induce plasminogen production, and does not specify compression injury.
Cooper et al discusses formation of scar tissue after contusive spinal cord injury (title). The pathway to fibrotic scarring goes through the fibronectein Extra Domain A domain, but eliminating this protein did nothing to glial scarring (abstract). This reference teaches that compressive spinal cord injury, a subset of the spinal cord injury of Davies et al, is similar in forming scar tissue.
Therefore, it would be obvious to use the methods of Davies et al to treat the compressive spinal cord injury of Cooper et al, as Cooper et al discuss many of the same issues as Davies et al does. As this is a genus (the spinal cord injury of Davies et al) species (the compressive injury of Cooper et al) relationship between the two papers, an artisan in this filed would attempt this therapy with a reasonable expectation of success.
However, as the effects of the therapy of Davies et al are mediated via plasminogen, it is obvious to use plasminogen instead of decorin, to avoid off target effects from decorin and to better control the plasminogen levels. As Davies et al describes the benefits of decorin therapy that run through plasminogen and plasmin, an artisan in this field would attempt this modification with a reasonable expectation of success.
Davies et al renders obvious plasminogen treatment for acute spinal cord injury. Cooper et al renders obvious compression spinal injuries, rendering obvious claim 1.
Davies et al uses human decorin, and the therapy would reasonably be used on human patients, rendering obvious human plasminogen and claims 12 and 15.
Davies et al discusses healing the damage, rendering obvious claims 19-24.
There is no mention of needing a second active ingredient, rendering obvious claim 25.
response to applicant’s arguments
Applicant argues that there is no teaching or suggestion to administer plasminogen, that decorin is different than plasminogen, and so is not interchangeable, that local administration of two plasminogen variants does not produce thrombolysis, and that plasmin activity can be harmful.
Applicant's arguments filed 17 March, 2026 have been fully considered but they are not persuasive.
Applicant argues that there is no teaching or suggestion to administer plasminogen. Davies et al teaches that plasminogen will provide a benefit. While the reference does not administer that protein, it is clear that the effects are mediated by it, rendering it an obvious variant.
Applicant argues that decorin is different than plasminogen, and not interchangeable. However, Davies et al makes clear that plasminogen will provide a benefit.
Applicants argue that two plasminogen variants do not produce thrombolysis without a plasminogen activator. This is not exactly correct. The reference clearly shows that adding a plasminogen activator is helpful, and that the two plasminogen variants without the plasminogen activator are less helpful (abstract). In any event, this is a reference discussing treatment of a very different disorder; it is not clear that the benefits described by Davies et al are applicable to the experiment described by the reference cited by applicants.
Applicants argue that plasminogen can be harmful. The evidence for this is a reference discussing the harmful effects of plasmin in a different disorder. There are two issues with this argument. First, it is not clear that the fact that a compound can be detrimental for a different disorder means it will be detrimental for the disorder claimed by applicants. Chemotherapy is, famously, associated with hair loss (Wikramanayake et al, Curr. Oncol. (2023) 30 p3609-3626, abstract). It is clear that it would be counterproductive to treat male pattern balding with chemotherapy. Yet that does not mean that chemotherapy would be useless to treat cancer. Second, the fact that a therapeutic has detrimental effects in addition to beneficial effects is a side effect. The courts have ruled that side effects, and the tradeoff of efficacy and side effects, is the purview of the FDA, not the patent office (MPEP2107.03 (I)(V)). In other words, side effects of a therapy do not play a role in the patentability determination.
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.
first rejection
Claims 1, 12, 15, and 18-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 19/127,079 (reference application) in view of Franz et al (J. Neurophysiol. (2019) 122 p1174-1185).
Competing claim 1 is a method of promoting degradation of TDP-43, comprising administering any of a number of compounds in the plasminogen pathway. Competing claim 2 specifies a Markush group of therapeutics, including plasminogen.
The difference between the competing claims and the examined claims is that the competing claims do not discuss compressive spinal cord injury.
Franz et al discusses TDP-43 in the context of TBI and ALS (p1177, 1st column, 1st paragraph). This protein is postulated to be related to the pathology of the disorders (p1179, 2nd column, 2nd paragraph), with some evidence that the protein itself is the problem (p1180, 2nd column, 1st paragraph). Note that it also shows up in the spinal cords of athletes that have had impact injuries (p1175, 2nd column, 2nd paragraph).
Therefore, it would be obvious to use the method of the competing claims to treat the compressive spinal injuries of Franz et al, to remove the TDP-43 in the spine which is suggested to be pathological. As this is the purpose of the competing claims, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
second rejection
Claims 1, 12, 15, and 18-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 15 of copending Application No. 19/127,091 (reference application) in view of Franz et al (J. Neurophysiol. (2019) 122 p1174-1185).
Competing claim 1 describes a means of removing a pathological protein, comprising administering a compound in the plasminogen pathway. Competing claim 3 lists a Markush group of compounds, including human plasminogen. Competing claim 15 lists a Markush group of proteins that can be removed, including TDP-43.
The difference between the competing claims and the examined claims is that the competing claims do not discuss compressive spinal cord injury.
Franz et al discusses TDP-43 in the context of TBI and ALS (p1177, 1st column, 1st paragraph). This protein is postulated to be related to the pathology of the disorders (p1179, 2nd column, 2nd paragraph), with some evidence that the protein itself is the problem (p1180, 2nd column, 1st paragraph). Note that it also shows up in the spinal cords of athletes that have had impact injuries (p1175, 2nd column, 2nd paragraph).
Therefore, it would be obvious to use the method of the competing claims to treat the compressive spinal injuries of Franz et al, to remove the TDP-43 in the spine which is suggested to be pathological. As this is the purpose of the competing claims, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
third rejection
Claims 1, 12, 15, and 18-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/022,084 (US 20230302102) (reference application) in view of Boussios et al (Anticanc. Res. (2018) 38 p4987-4997).
Competing claim 1 describes a method of treating tumors, comprising administering plasminogen.
The difference between the competing claims and the examined claims is that the competing claims do not discuss compression of the spine.
Boussios et al discusses metastatic spinal cord compression (title). This is one of the most devastating complications of cancer, causing pain, paralysis, sensory loss, and loss of sphincter control (abstract). This reference discusses tumors causing compression injury to the spine.
Therefore, it would be obvious to treat the tumors of Boussios et al with the plasminogen of the competing claims, as a simple substitution of one known element (the tumor patients of the competing claims) for another (the patients of Boussios et al) yielding expected results (treatment of tumors). As this is a genus/subgenus relationship, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
fourth rejection
Claims 1, 12, 15, and 18-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16 and 17 of copending Application No. 17/595,113 (US 20220218799) (reference application) in view of Aundhakar et al (Adv. Biomed. Res (2017) 6 95)
Competing claim 16 describes a method of treating ALS, comprising administering plasminogen, specifically, SEQ ID 2 (identical to SEQ ID 2 of the examined claims) or a variant. Competing claim 17 lists repair of inflammation of the spinal cord as an effect of the therapy.
The difference between the competing claims and the examined claims is that the competing claims do not discuss spinal cord compression injury.
Aundhakar et al discuss a rare variant of ALS, Hirayama’s disease (title). At least part of the pathogenesis is considered due to spinal cord compression (3d pate, 1st column, 1st paragraph).
Therefore, it would be obvious to treat the patients of Aundhakar et al with the therapy of the competing claims, to treat the ALS of those patients, as discussed by the competing claims. As this is a subset of the disease of the competing claims, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
fifth rejection
Claims 1, 12, 15, and 18-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of copending Application No. 17/797,504 (US 20230084586) (reference application) in view of Bashir et al (Neurosurg. (2000) 47 p637-643).
Competing claim 1 describes a method of treating MS, comprising administering plasminogen. Competing claim 6 specifies SEQ ID 2, identical with SEQ ID 2 of the examined claims, and variants.
The difference between the competing claims and the examined claims is that the competing claims do not discuss spinal cord compression injury.
Bashir et al discuss surgery for spinal cord compression in patients with MS (title). This provided some improvement in some patients (abstract).
Therefore, it would be obvious to treat the patients of Bashir et al with the therapy of the competing claims, as they both are treating the same disorder (MS). As this is the same disorder, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
sixth rejection
Claims 1, 12, 15, and 18-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1and 12 of copending Application No. 17/798,824 (US 20230081922) (reference application) in view of Agostinello et al (Spinal Coird (2019) 57 p41-48).
Competing claim 1 describes a method of treating pneumonia, comprising administering plasminogen. Competing claim 12 specifies natural or synthetic human plasminogen.
The difference between the competing claims and the examined claims is that the competing claims do not specify a nerve injury.
Agostinello et al discuss predictors of pneumonia in spinal cord injury patients (title). Pneumonia is the dominant complication following spinal cord injury, and profoundly affects morbidity (abstract). Some patients had spinal cord compression (p42, 1st column, 5th paragraph).
Therefore, it would be obvious to treat the patients of Agostinello et al with the therapy of the competing claims, to treat the pneumonia which often comes with spinal cord injury. As this is the same disorder as the competing claims are treating, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
seventh rejection
Claims 1, 12, 15, and 18-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 12, and 14 of copending Application No. 17/914,271 (US 20230346897) (reference application) in view of Aundhakar et al (Adv. Biomed. Res (2017) 6 95)
Competing claim 1 describes a method of promoting the degradation of a misfolded protein, comprising administering plasminogen. Competing claim 7 mentions using human plasminogen as the therapeutic. Competing claims 12 and 14 specify treatment of a neurodegenerative disorder, specifically, ALS.
The difference between the competing claims and the examined claims is that the competing claims do not discuss spinal cord compression injury.
Aundhakar et al discuss a rare variant of ALS, Hirayama’s disease (title). At least part of the pathogenesis is considered due to spinal cord compression (3d pate, 1st column, 1st paragraph).
Therefore, it would be obvious to treat the patients of Aundhakar et al with the therapy of the competing claims, to treat the ALS of those patients, as discussed by the competing claims. As this is a subset of the disease of the competing claims, an artisan in this field would attempt this therapy with a reasonable expectation of success.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
additional rejections
Claims 1, 3, 4, 12, 13, 15, and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/037,300 (US 20240000904), US 12,576,139, or US 11,007,253.
The rationale behind these rejections is similar to the previous rejections, and will not be restated here.
response to applicant’s arguments
Applicant requests this rejection be held in abeyance until the application is otherwise allowable. However, until it is overcome, it will remain valid.
New Rejections
Claim Rejections - 35 USC § 112(a)
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.
first rejection, new matter
Claim 25 is 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.
New claim 25 requires that the plasminogen be the only active ingredient. There is no support for this amendment. Paragraph 69 discusses not less than one active compound, but it is clear from the rest of the paragraph that it is talking about one or more additional compounds to the plasminogen. Thus, this amendment constitutes new matter.
second rejection, enablement
Claim 26 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The MPEP states “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue.’ These factors include, but are not limited to: 1) the breadth of the claims; 2) the nature of the invention; 3) the state of the prior art; 4) the level of one of ordinary skill; 5) the level of predictability in the art; 6) the amount of direction provided by the inventor; 7) the existence of working examples; and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure” (MPEP 2164.01(a).
1 and 2) the breadth of the claims and the nature of the invention: Claim 1, from which claim 26 depends, is a method for treating a spinal cord compression injury, comprising administering plasminogen. Competing claim 26 requires systemic dosing of the plasminogen.
3) the state of the prior art: Wu et al (Arch. Neurol. (1973) 28 p64-66) states that very little plasminogen will cross the blood brain barrier (p66, 3d column, 2nd paragraph).
4) the level of one of ordinary skill: The level of skill in the art is high.
5) the level of predictability in the art: The blood brain barrier has been studied (and cursed at) for a very long time, leading to a modest level of predictability.
6 and 7) the amount of direction provided by the inventor and the existence of working examples: There is a mention of systemic administration, but no examples are given.
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure: Plasminogen cannot cross the blood brain barrier. This means that treating a disorder behind the blood brain barrier, such as CNS injury, requires an administration route that is on the other side of the barrier, which systemic administration is not. Thus, it will take undue experimentation to use the method as claimed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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