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 .
Status of the Application
Applicant’s remarks and amendment submitted on 01/12/2026 are acknowledged.
Claims 1-12 and 14-20 are pending.
Claims 1-8, 10-12, and 14-20 are amended.
Claim 13 is canceled.
Claims 3, 10, 12, 14-17, and 19 are withdrawn.
Claims 1-2, 4-9, 11, 18, and 20 have been examined on the merits.
It is acknowledged that Applicant elects without traverse in the 01/12/2026 response the species: (1) a method of treating a patient by administering Glu-plasminogen, and (2) a thrombotic event along with a subspecies of deep vein thrombosis, respectively, in response to the two species requirements set forth in the prior office action.
Upon searching and further consideration, Examiner has rejoined the subspecies of disseminated intravascular coagulation to be examined together with the elected subspecies of deep vein thrombosis in the elected species (2). The remaining of the species election requirement is still maintained.
Claims 3, 10, 12, 14-17, and 19 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Specification
The abstract of the specification is objected to as it contains legal phraseology. The form and legal phraseology often used in patent claims, such as "said", should be avoided. Appropriate correction is required.
The disclosure of the specification is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 40/line 29 and page 41/line 8). References to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code.
Priority
This application, U.S. Application number 18/360612, is a DIV of U.S. Application number 16/491408 filed on 09/05/2019, now issued as U.S. Patent number 11759505, which is a national stage entry of International Application NO. PCT/EP2018/055984, filed on 03/09/2018, which claims for foreign priority under 35 U.S.C. 119(a)-(d) to foreign application EP 17160106.5, filed on 03/09/2017.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/27/2023, 12/04/2023, and 10/24/2025 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97., and have been considered by the examiner.
Claim Rejections - 35 USC § 112(b), or 112, Second Paragraph
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 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.
Claim 1 is indefinite because of the recited limitation “a sufficient amount of Glu-plasminogen”. Given that the claim is directed to a method of treatment, one of skill in the art should be provided with clear indication about the dosage. However, the term “sufficient amount” is not defined in the specification. In the absence of a clear definition as to what is considered as “sufficient amount”, the recited limitation is just descriptive or a term of degree of the dosage, and the scope of the limitation is not clear. Thus, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the subject matter for which Applicants seek patent protection.
Claim 2 is indefinite due to the recitation “the same species”. The claim does not recite any comparison phrase. It is unclear which specific animal the recited species is same as. For the purpose of examination, it is assumed that the species is the same as the patient. The claim also recites the limitations: “the ratio of alpha-2-antiplasmin vs. Glu-plasminogen”, “the blood of the patient”, “the average ratio”, “the level of Glu-plasminogen”, and “the average level”. It is unclear what specific ratio, level, or blood sample these recited limitations refer to.
Claim 8 is indefinite due to the recitation of “thrombotic event is … an acute or chronic inflammation causing a local or generated imbalance of the fibrinolytic system like acute transplant rejection”. It is unclear whether the recited thrombotic event is referred as “an acute or chronic inflammation”, or as “generated imbalance of the fibrinolytic system” caused by the inflammation. Furthermore, the limitation “like acute transplant rejection” renders the claim indefinite because it is unclear whether the limitation following the term “like” is a part of the claimed invention. See MPEP § 2173.05(d).
The remaining claims are rejected for depending from an indefinite claim.
Claim Rejections - 35 USC § 112(a) or 112, First Paragraph
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claim 2 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(s), at the time the application was filed, had possession of the claimed invention.
The claim 2 is directed to a method for treating a patient suffering from a thrombotic event by administering a sufficient amount of Glu-plasminogen to the patient, with the following limitations to define the patient: (a) a ratio of alpha-2-antiplasmin vs. Glu-plasminogen in the patient’s blood is at least 1.1-fold higher than an average ratio found throughout a population of the same species; and/or (b) a level of Glu-plasminogen in the patient’s blood is at least 1% lower than an average level found throughout a population of the same species. It is noted that the “species” and “population” recited in the claim can be any animal species and any population having any age or any physical or healthy status. As such, the average ratio and average level used for comparison with the patient in the claimed method are variables from all species and populations encompassed by the claim.
The specification of the instant application (e.g. para 0401 of PGPUB US 2023/0381289) discloses only a single control population of 55 subjects without specifically defined species, used for detecting a range of average ratio of A2AP/PLG and a range of average level of PLG. However, There is no disclosure or guidance in the specification or in the prior art regarding how to effectively determine an average blood level of Glu-plasminogen and an average ratio of alpha-2-antiplasmin vs. Glu-plasminogen in any population for all of the species and populations encompassed by the claim.
In order for the written description provision of 35 USC 112, first paragraph to be satisfied, Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed. Adequate written description requires more than a mere statement that it is part of the invention.
Therefore, the full breadth of an average ratio of alpha-2-antiplasmin vs. Glu-plasminogen and an average level of Glu-plasminogen found throughout a population of the same species encompassed by the claim does not meet the written description provision of 35 USC 112, first paragraph.
Claim Rejections - 35 USC § 102
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.
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 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.
Claims 1, 9, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Susilo et al. (CN 1768138, 2006, Machine-translated English version is attached).
This is a rejection of the Generic claims with respect to the species of thrombotic event.
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).
Since the plasminogen species used for treating thrombotic event, taught by Susilo et al., are sufficiently limited, one would immediately envisage the use of Glu-plasminogen for treating thrombotic event.
Therefore, in view of the teachings of Susilo et al., the method of Claims 1, 9, and 18 is anticipated by the method of Susilo et al.
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 of this title, 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.
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 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.
Claims 1, 5-6, 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 is attached).
The teachings of Susilo et al. are described above.
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 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). 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 2 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Susilo et al. (CN 1768138, 2006, Machine-translated English version is attached), as applied to Claims 1, 5-6, 8-9, 18, and 20, further in view of Laurin et al. (WO 2017/077380, 2017, filed on 11/3/2026, Derwent Abstract is attached).
The teachings of Susilo et al. are described above.
Regarding the claims 2 and 4, Susilo et al. further 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. 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.
It would have been obvious to administer Glu-plasminogen to a patient suffered 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, 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).
Regarding the level of Glu-plasminogen in the patient recited in the claim 2, Laurin et al. teach the reduced plasmatic plasminogen activity in the plasminogen-deficient patient is ≤ 70% of the normal plasminogen activity (page 3/para 2/lines 10-11), and the patient’s plasminogen activity level is increased by at least 1% of the normal plasminogen activity after Glu-plasminogen administration, which either read or overlap with the claimed range “at least 1%”. It is noted that the normal plasminogen activity taught by Laurin et al. is a normalized/averaged level of Glu-plasminogen in a healthy population of the same species as the patient, which is an obvious variant of the average level recited in the claim. Thus, the teachings of the cited prior art render the claim to be obvious.
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 is attached), as applied to Claims 1, 5-6, 8-9, 18, and 20, further in view of Naeye (New England Journal of Medicine, 1961, 265(18): 867-871).
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 of Susilo 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
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-2, 4-8, 11, 18, and 20 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 31, 33-34, 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.
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 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 1-2, 4-8, 11, 18, and 20 of the instant application is anticipated by or deemed obvious over the method of claims 31, 33-34, 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, 33-34, 37-41, 44-46, 48-56, and 58-62 of copending Application No. 17422962, as applied to Claims 1-2, 4-8, 11, 18, and 20, further in view of Susilo et al. (CN 1768138, 2006, Machine-translated English version is attached).
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 1-2, 4-9, 11, 18, and 20 of the instant application is anticipated by or deemed obvious over the method of claims 31, 33-34, 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.
Conclusion
No claim is in condition for allowance.
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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