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 .
Remarks
The amendments and remarks filed on 06/08/2026 have been entered and considered. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior office action. The rejections and/or objections presented herein are the only rejections and/or objections currently outstanding. Any previously presented objections or rejections that are not presented in this Office Action are withdrawn. Claims 1, 3-12, and 14-20 are pending; Claims 2 and 13 are cancelled; Claims 1 and 8 are amended; Claims 3, 10, 12, 14-17, and 19 are withdrawn; and Claims 1, 4-9, 11, 18, and 20 are under examination.
Withdrawal of Objections
The objection to abstract is withdrawn due to the amendment to the abstract filed on 6/8/2026.
The objection to the specification for containing an embedded hyperlink is withdrawn due to the amendment to the specification filed on 06/08/2026.
Withdrawal of Rejections
The rejection of Claim 2 under 35 U.S.C. 112(a), as failing to comply with the written description requirement, is withdrawn due to the cancellation of the claim filed on 06/08/2026.
The rejection of claims 1-2, 4-9, 11, 18 and 20 under 35 U.S.C. 112(b) in the previous office action is withdrawn due to the amendment to or cancellation of claims.
The rejection of Claims 1, 9, and 18 under 35 U.S.C. 102(a)(1) as being anticipated by Susilo et al. is withdrawn due to the amendment to the claims.
The rejection of claims 1, 5-6, 8-9, 18, and 20 under 35 U.S.C. 103 over Susilo et al. is withdrawn due to the amendment to the claims.
The rejection of claims 1, 5-9, 11, 18, and 20 under 35 U.S.C. 103 over Susilo et al. in view of Naeye is withdrawn due to the amendment to the claims.
Claim Rejections - 35 USC § 112(b), or 112, Second Paragraph
Claims 1, 4-9, 11, 18, and 20 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 pre-AIA the applicant regards as the invention. This rejection is maintained.
Claim 1 is indefinite due to the recitation: “the ratio of alpha-2-antiplasmin vs. Glu-plasminogen … in the blood of the patient … the average ratio found in a control population”, “the level of Glu-plasminogen in the blood of the patient … the average level found in the control population”. It is noted that the “control population” recited in the claim is not defined in the specification, and its scope encompasses any control population, such as a healthy population, an unhealthy population, and a population in a specific age group (e.g. adult, youth, or elderly population). Thus, the “average ratio” of alpha-2-antiplasmin vs. Glu-plasminogen and the “average level” of Glu-plasminogen are variable among different control populations. It is unclear which specific average ratio or average level the recited limitations “the average ratio” and “the average level” refer to, respectively. Furthermore, the claim recites the limitations: “the ratio of … in the blood of the patient” and “the level of Glu-plasminogen in the blood of the patient”. It is unclear which specific ratio, level of Glu-plasminogen, or blood sample these limitations refer to.
The remaining claims are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 103
Claims 1, 4-6, 8-9, 18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Susilo et al. (CN 1768138, 2006, Machine-translated English version of record), as applied to Claims, further in view of Laurin et al. (WO 2017/077380, 2017, filed on 11/3/2026, Derwent Abstract of record).
Susilo et al. teach a method for production of functional plasminogen in a genetically engineered microorganism, as well as the use of the plasminogen (a method of using the plasminogen) for treating or preventing thrombotic event in a patient, wherein the plasminogen is glutamic acid-plasminogen (Glu-plasminogen) or lysine-plasminogen (Lys-plasminogen), and the plasminogen is a human plasminogen; wherein the plasminogen is used as an antithrombotic and anticoagulant agent; wherein the plasminogen forms a part of a pharmaceutical composition comprising the plasminogen and a pharmaceutically acceptable carrier; and wherein the use of the plasminogen for treating thrombotic event comprises administering the plasminogen/pharmaceutical composition at an effective amount locally, orally, or parentally through injection or transfusion to the patient (claims 1, 3, 6, 26, 33, 40-44, and 50-55; page 4/paras 7-8, page 11/last para -page 13/para 1, page 13/para 6, page 14/para 1). Susilo et al.also teach administering Glu-plasminogen for treating patients having plasminogen deficiency conditions, wherein the conditions cause a thrombosis event (page 13/para 2: lines 1, 3, 5). Susilo et al. further teach various thrombotic events to be treated by the plasminogen, and list them in a Markush group, in which both deep vein thrombosis and disseminated intravascular coagulation are included (see Claims 43 and 55). Susilo et al. further teach the human plasminogen used for treating patients acts as a key player of the human fibrinolytic system for controlling breakdown of blood clots (pages 1-2), and Examiner notes it is well known in the art that the thrombotic events such as deep vein thrombosis treated by the method of Susilo et al. are human diseases. As such, patients of Susilo et al. comprise human patients.
The method of Susilo et al. differs from the method of the claims 1, 4, 9 and 18 in that Susilo et al. do not expressively teach an acquired plasminogen deficiency as the plasminogen deficiency condition, and Susilo et al. are silent about a specific level of the deficiency compared to a normal level of a control population.
It would have been obvious to administer Glu-plasminogen to a human patient suffering from acquired plasminogen deficiency in the method of Susilo et al. for treating thrombotic event caused by acquired plasminogen deficiency, because the plasminogen deficiency conditions taught by Susilo et al. encompasses the acquired plasminogen deficiency and Susilo et al. expressively teach the plasminogen deficiency conditions cause thrombotic event. Furthermore, it is well known in the art that the acquired plasminogen deficiency causes thrombotic event in human, as supported by Laurin et al., who teach a method of supplementing to a plasminogen-deficient patient an effective dose of Glu-plasminogen for increasing the patient’s plasminogen activity level by at least 1% of the normal plasminogen activity (Claim 1, page 3/para 2/lines 1-5), wherein the plasminogen-deficient subject has an acquired plasminogen-deficient which is related to a thrombotic event (page 3/para 2/lines 4-5); wherein a level of plasminogen activity in the plasminogen-deficient patient is ≤ 70% of the normal plasminogen activity (page 3/para 2/lines 10-11); and wherein the plasminogen-deficient patient is a human patient (page 3/para 2).
Regarding the level of Glu-plasminogen in the patient recited in the claim 1, Laurin et al. teach the reduced plasmatic plasminogen activity in the plasminogen-deficient patient is ≤ 70% of the normal plasminogen activity, and the patient’s plasminogen activity level is increased by at least 1% of the normal plasminogen activity after Glu-plasminogen administration. It is noted that the normal plasminogen activity taught by Laurin et al. is a normalized or averaged level of Glu-plasminogen in a healthy control population; and the reduced level, ≤ 70% of the normal/average level, taught by Laurin et al. meets the claimed reduced level of at least 1%. Thus, the teachings of the cited prior art render the claims to be obvious.
Regarding the specific thrombotic events “deep vein thrombosis” and “disseminated intravascular coagulation” recited in the claims 6, 8, and/or 20, Susilo et al. teach various thrombotic events including both deep vein thrombosis and disseminated intravascular coagulation. In view of the teachings of Susilo et al., it would have been obvious to one of ordinary skill in the art to administer a sufficient amount of Glu-plasminogen to a subject suffering from deep vein thrombosis or disseminated intravascular coagulation for treating the patient, because Susilo et al. specifically teach using the plasminogen for treating these thrombotic events.
Regarding the claim 5, disseminated intravascular coagulation treated by the method of Susilo et al. is caused by micro-coagulation disorder, as evidenced by the specification of the instant application (see para 242/last 4 lines of PGPUB US 2023/0381289 of the instant application). Therefore, the claim 5 would have been obvious over Susilo et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 7 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Susilo et al. (CN 1768138, 2006, Machine-translated English version of record) in view of Laurin et al. (WO 2017/077380, 2017, filed on 11/3/2026, Derwent Abstract of record), as applied to Claims 1, 4-6, 8-9, 18, and 20, further in view of Naeye (New England Journal of Medicine, 1961, 265(18): 867-871, of record).
The teachings of Susilo et al. are described above.
Regarding the claims 7 and 11, Susilo et al. do not specifically teach the thrombotic event is caused by an acquired increase of a plasmin inhibitor/alphs2 antiplasmin. However, Susilo et al. teach administering Glu-plasminogen for treating the thrombotic event. Regardless of what causes a thrombotic event, all thrombotic events involve the formation of blood clots (thrombi) within vessels. Given Susilo et al. teach the plasminogen/Glu-plasminogen is used as an antithrombotic and anticoagulant agent for treating thrombotic events (page 11/last 2 lines, page 12/lines 5-9), it would have been obvious to apply the method suggested by Susilo et al. and Laurin et al. for treating the thrombotic event caused by an acquired increase of a plasmin inhibitor/alphs2 antiplasmin. Furthermore, it is well known in the art that alpha2 antiplasmin is an plasmin inhibitor that inhibits plasmin, and an increase of plasmin inhibitor in patients leads to a significant decrease at levels of plasmin and plasminogen, which are consequently related to thrombotic events in the patients, as supported by Susilo et al. (page 2/para 5 and page 6/para 4) and by Naeye (title; page 871/left col/last full para; page 868: left col/lines 2-4 and right col/lines 3-7; page 869/right col: para 2/lines 9-12 and para 3/lines 7-9). Thus, it would have been obvious to apply the method of Susilo et al. for providing the plasminogen to the patient for treating the thrombotic event caused by an acquired increase of plasmin inhibitor/alphs2 antiplasmin.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
Claims 1, 4-8, 11, 18, and 20 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 31, 34, 37-41, 44-46, 48-56, and 58-62 of copending Application No. 17/422962. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. This rejection is maintained.
The claims of the copending ‘926 application are directed in part to a method for treating thrombotic events in a human patient with an acquired Glu-plasminogen deficiency, comprising: administering to the patient with a composition comprising sufficient amount of Glu-plasminogen, wherein the acquired Glu-plasminogen deficiency is caused by increased Glu-plasminogen consumption, decreased biosynthesis of Glu-plasminogen, or a combination of both; wherein the patient has developed microthrombi resulting in a thrombosis or embolization of blood vessels; wherein the patient suffers from at least one ischemic region; wherein the patient suffers from deep vein thrombosis, pelvic vein thrombosis, pulmonary embolism, an infarction of any organ, retinal vein occlusion, disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), an angiopathy coincidence with thrombotic events in capillary flow path, diabetic angiopathy, thrombophlebitis, or a combination of two or more thereof; wherein the patient suffers from disseminated intravascular coagulation (DIC), acute kidney/renal injury (AKI), sepsis, or a combination of two or more thereof; wherein the patient has a lower blood level of Glu- plasminogen than the average blood level of Glu-plasminogen found throughout a healthy human population of the same species as the patient; wherein a level of Glu-plasminogen in the patient's blood is determined prior to the administration of Glu-plasminogen is at least 10% (mol/mol) lower in comparison to the average level of Glu-plasminogen found throughout a healthy human population of the same species as the patient; wherein the administration is conducted if the level of Glu-plasminogen in the patient is at least 10% (mol/mol) lower in comparison to the average level found throughout a healthy human population; and wherein the patient is administered with the Glu-plasminogen at least once with a dose in the range of 0.01 to 100 mg/kg body weight.
Regarding the claims 7 and 11, the claims of the ‘926 application do not specifically teach the thrombotic event is caused by an acquired increase of a plasmin inhibitor/alphs2 antiplasmin. However, the claims of the ‘926 application teach administering Glu-plasminogen for treating thrombotic events involved with thrombi formation. Regardless of what causes a thrombotic event, all thrombotic events involve the formation of blood clots (thrombi) within vessels. Thus, it would have been obvious to modify the claimed method of the ‘926 application by administering Glu-plasminogen for treating a thrombotic event caused by an acquired increase of a plasmin inhibitor or alphs2 antiplasmin.
Therefore, the method of Claims 1, 4-8, 11, 18, and 20 of the instant application is anticipated by or deemed obvious over the method of claims 31, 34, 37-41, 44-46, 48-56, and 58-62 of copending Application No. 17422962.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claim 9 is provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 31, 34, 37-41, 44-46, 48-56, and 58-62 of copending Application No. 17422962, as applied to Claims 1, 4-8, 11, 18, and 20, further in view of Susilo et al. (CN 1768138, 2006, Machine-translated English version of record). This rejection is maintained.
The subject matter of the claims of the copending ‘926 application is described above.
The teachings of Susilo et al. are described above.
Regarding the claim 9, the claims of the copending ‘926 application do not expressively teach that Glu-plasminogen is a part of a pharmaceutical composition comprising the Glu-plasminogen and at least one pharmaceutically acceptable carrier. It would have been obvious to combine the Glu-plasminogen with a pharmaceutically acceptable carrier to form a pharmaceutical composition to be administered to a patient in the claimed method of the copending ‘926 application for treating thrombotic events, because it is well known to combine Glu-plasminogen with a pharmaceutically acceptable carrier to form a pharmaceutical composition for treating thrombotic events, and it is a common practice in the art to add one pharmaceutically acceptable to a pharmaceutical composition for treating patients, as supported by Susilo et al. described above.
Therefore, in view of cited prior art, the method of Claims 1, 4-9, 11, 18, and 20 of the instant application is anticipated by or deemed obvious over the method of claims 31, 34, 37-41, 44-46, 48-56, and 58-62 of copending Application No. 17/422962.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Response to Arguments
Applicant's arguments about the objections to the specification/abstract as well as the rejection of claim 2 under 35 USC 102(a) in the response filed on 06/08/2026 (pages 6-8) have been fully considered but they are moot because the objections and rejection have been withdrawn as indicated above.
Applicant's arguments about the rejection of claims 1, 4-9, 11, 18, and 20 under 35 USC 102(b) in the 06/08/2026 response (pages 6-7) have been fully considered. Applicant’s arguments based on the disclosure of the specification/para [0461] is not persuasive. It is noted that the features (i.e. A2AP/PLG ratios in a healthy control group and a patient group) upon which Applicant relies are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As indicated above, the amended claim 1 still has indefinite issues (see pages 3-4 of this action for details). With regard to Applicant’s remaining arguments in the response, they are moot because the rejection has been withdrawn as indicated above.
Applicant's arguments about the rejections of Claims 1, 5-9, 11, 18, and/or 20 under 35 USC 102(a)(1) or 103 as being anticipated by or over Susilo et al. alone or in combination with Naeye in the 06/08/2026 response (pages 8-11) have been fully considered but they are moot, because the rejections have been withdrawn, as indicated above.
Applicant's arguments about the claim rejection under 35 USC 103 over Susilo et al. in view of Laurin in the 06/08/2026 response (pages 9-10) have been fully considered. Applicant's arguments about Susilo et al. and Laurin in page 10 of the response are not persuasive for the following reasons.
Examiner first notes that the limitation (a) (a ratio being at least 1.1 fold higher than a control population) in the newly amended claim 1 is an optional limitation. The combined teachings of Susilo et al. and Laurin suggest the limitation (b) (a level being at least 1% lower than a control population) in the amended claim 1, thus meeting the claimed limitation and rendering the amended claim 1 to be obvious as indicated in the 103 rejection above. With regard to the teachings of the cited prior art, Susilo et al. teach a method of treating a thrombosis event in a patient having plasminogen deficiency by administering Glu-plasminogen to increase a level of Glu-plasminogen in the patient; and patients having plasminogen deficiency treated by the method of Susilo encompass those patients having Glu-plasminogen at levels of at least 1% lower than an average/normal level of a healthy control population. Laurin et al. teach administering Glu-plasminogen to a patient having Glu-plasminogen at ≤ 70% of normal level of healthy population for treating plasminogen-deficiency, which results in at least 1% increase of the patient’s plasminogen activity level. Examiner notes that the ≤ 70% of normal/average level taught by Laurin et al. meets the claimed limitation about a level of Glu-plasminogen being at least 1% lower than an average level of a control population. One of ordinary skill in the art would have been motivated to treat patients having plasminogen at levels of at least 1% lower than a normal level of a healthy/control population in the method of Susilo et al. and has a reasonable expectation of success for increasing Glu-plasminogen levels and treating a thrombotic event in the patients, because it is well known in the art that administering Glu-plasminogen to a plasminogen-deficient patient at the levels of at least 1% lower than a normal level effectively increases the patient’s plasminogen activity level, as supported by Laurin et al.
Overall, the conclusion of the obviousness of the newly amended claims 1, 4-9, 11, 18, and 20 has been established for all the reasons indicated above.
Applicant’s comments about the double patenting rejections in the 06/08/2026 response (page 11) are acknowledged.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600.
/Qing Xu/
Patent Examiner
Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656 (p.r)
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