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 .
Restriction/Election
Applicant’s election of Group I (Claims 1-6 and 9-18), as well as Applicant’s election of Species 1F (motor neuron disease), Species 3C (plasminogen), and Subspecies 3C1 (SEQ ID NO.: 2 or 6 or 8 or 10 or 12), is acknowledged.
Claims 7 and 8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Group II, there being no allowable generic or linking claim. In addition, Claim 17 is withdrawn as being drawn to nonelected plasminogen subspecies; all limitations relating to said nonelected species are also withdrawn from further consideration at this time. Election was made without traverse, in the timely reply filed on 17 September 2025 to the Restriction/Election Office Action mailed on 17 July 2025.
Status of Claims
Claims 7, 8 and 17 show incorrect status identifiers. Applicant is reminded that claims 7, 8 and 17 should be labeled: “(Withdrawn)”; remaining claims should be identified appropriately (MPEP 714 (II)(C)(A)) (See 37 CFR 1.121 (c)).
Appropriate correction is required.
Applicant is required to provide a new claim set showing correct status identifiers in the response to this Office Action.
Claims 1-11 and 16-18 are pending.
Claims 1-6, 9-11, 16 and 18 are rejected.
Claims 5-6 and 18 are objected to.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. §119(e) or under 35 U.S.C. §120, §121, or §365(c) is acknowledged. This application is a 371 of PCT/CN2021/131185, filed on 11/17/2021.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. §119 (a)-(d). The certified copy of CHINA PCT/CN2020/129459, filed on 11/17/2020, was submitted on 16 May 2023.
Applicant has complied with all of the conditions for receiving the benefit of an earlier filing date under 35 U.S.C. §120 or §365(c).
However, it is noted that the number of figures (3) filed with foreign priority document CN PCT/CN2020/129459 is short of the number of drawings filed with the 371 document which contains 15 figures. Because the foreign priority document is not in English, it is not clear if this document contains the text or data which describes those figures that appear in the PCT document, but not in the foreign priority document. Applicant should submit an English translation of the foreign priority document in order for the Office to be able to determine which of the instant claims have written support in said foreign priority document.
Therefore, claims 1-6, 9-11, 16 and 18 have the effective filing date of the 371 document which is 17 November 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 17 September 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
Drawings
The drawings were received on 16 May 2023. These drawings are accepted.
Claim Objections
Claims 5-6 and 18 are objected to because of the following informalities:
(1) Claim 5 recites: "The method according to claim 1, wherein the plasminogen has one or more uses or activities selected from the group consisting of:...", which should read: "The method according to claim 1, wherein the plasminogen has one or more activities selected from the group consisting of:..."
That is, the term 'uses' in the phrase 'one or more uses' is akin to so-called 'use claim' language which is subject to rejection under 35 USC §112(b) and/or 35 USC §101, and, therefore, the term should be removed.
(2) Claim 6 recites: "The method according to claim 1, wherein the subject is a subject suffering from injury of nerve or brain tissue caused by one or more diseases or conditions...", which should read: "The method according to claim 1, wherein the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions..."
(3) Claim 18 recites: "..., wherein the plasminogen is selected from Glu-plasminogen,..., micro-plasminogen, or delta-plasminogen, or a variant thereof retaining...", which should read: "..., wherein the plasminogen is selected from Glu-plasminogen,..., micro-plasminogen, delta-plasminogen, and a variant thereof retaining..."
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
35 U.S.C. § 112(b)
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.
Claim 5 is 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 5 is indefinite because the metes and bounds of the claimed subject matter are not clear.
(1) Claim 5 recites: "..., wherein the plasminogen has one or more uses or activities selected from the group consisting of: nourishing nerves, protecting nerves, promoting nerve regrowth, inhibiting nerve injury, promoting repair of wound tissue, and promoting wound healing."
Claim 5 recites the terms "nourishing nerves" and "protecting nerves".
However, it is not clear, for the purpose of prior art determination, what biophysiological or biochemical properties are exhibited by the plasminogen in order determine that nerve nourishment or protection has taken place. The terms are not explained, defined or described in the specification.
On the other hand, the terms appear to be (broad) genus limitations which would be considered to encompass other species limitations in the claim. For example, 'inhibiting nerve injury' could be considered to protect nerves. Similarly, 'promoting nerve regrowth' could be considered to be a way that nerves are nourished. Therefore, it is not clear which species would be covered by either of the genus terms (MPEP 2173.02 (I) and MPEP 2173.05 (h)).
For the purpose of compact prosecution, prior art which describes the biochemical or biophysical properties of plasminogen (or tPA or plasmin) as including the activities of nourishing nerves or protecting nerves, in general, or which include the activities of promoting nerve regrowth, inhibiting nerve injury, promoting repair of wound tissue, and/or promoting wound healing- or any other activity that would be considered to nourish or protect nerves- will be considered to be applicable prior art.
35 U.S.C. § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. §112(d) or pre-AIA 35 U.S.C. §112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 recites: "The method according to claim 1, wherein the plasminogen further increases the expression and level of neurotrophic factors in the nerve tissue of the subject."
Claim 1 recites: "A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen."
The specification recites: "Nerve growth factor (NGF) is an important member of the neurotrophic factor family" (clean copy specification filed on 16 May 2023, pg. 39, para. [0101]).
Claim 3 does not further limit claim 1, because claim 1 describes increasing the level of NGF which is a neurotrophic factor and claim 3 describes increasing the expression and level of neurotrophic factors (which include NGF); i.e., claim 3 is broader than the parent claim.
Applicant may cancel the claim, amend the claim so as to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
For the purpose of examination, prior art which addresses the limitations of claim 1 will also be considered to address the limitations of claim 3.
Claim Rejections - 35 U.S.C. § 103
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.
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.
Claims 1-3, 5-6, 10-11 and 18 are rejected under 35 U.S.C. §103 as being unpatentable over Li (Pub. No. WO 2018/233604 A1; see English machine translation (EngMT) as NPL for page/para. numbers) in view of Bruno et al. ( PNAS, 2006, 103(17): 6735-6740).
Li addresses some of the limitations of claim 1.
Regarding claim 1, pertaining to a method comprising administering to a subject a therapeutically effective amount of plasminogen,
Li shows a method of treating a disease by modulating GLP-1/GLP-1R comprising administering to the subject an effective amount of plasminogen (pg. 5, para. #1). 'Therapeutically effective amount' or 'effective amount' refers to an amount of plasminogen sufficient to effect such prevention and/or treatment of a disease when administered to a mammal or other subject to treat the disease. The 'therapeutically effective amount' will vary depending on the plasminogen used, the severity of the disease and/or its symptoms of the subject to be treated, and the age, weight, and the like (pg. 19, para. 3).
Li does not explicitly show: 1) promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level [Claim 1]; and 2) wherein the plasminogen further increases the expression and level of neurotrophic factors in the nerve tissue of the subject [Claim 3].
Bruno et al. provides information from which one of ordinary skill in the art of administering plasminogen (or tPA (tissue type plasminogen activator) or plasmin) to a subject in order to treat a disease or condition, as shown by Li, would have expected that said plasminogen would have promoted the formation of mature NGF (and/or increased the level of NGF), by way of addressing the limitations of claims 1 and 3.
[See 35 USC §112(d) rejection above.]
Regarding claims 1 and 3, Bruno et al. shows a study which provides direct demonstration that the neurotrophin nerve growth factor (NGF) is released in the extracellular space in an activity-dependent manner in its precursor form (proNGF) and that it is in this compartment that its maturation takes place because of the coordinated release and the action of proenzymes and enzyme regulators. This converting protease cascade and its endogenous regulators (including tissue plasminogen activator, plasminogen, neuroserpin, precursor matrix metalloproteinase 9, and tissue inhibitor metalloproteinase 1) are colocalized in neurons (pg. 6735, column 1, Abstract). That is, it was investigated how proNGF is converted to mNGF (mature NGF) in the extracellular milieu upon its stimulus-coupled neuronal release. A mechanism involving plasminogen and the tissue plasminogen activator (tPA) was suspected (pg. 6736, column 1, para. 1). tPA converts plasminogen into the active protease plasmin, which ultimately cleaves proNGF into mNGF (pg. 6736, column 2, lines 6-8).
That is, promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF appears to be an inherent property of plasminogen as it is associated with tPA and plasmin.
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have expected that the method for treating a disease by administering to a subject a therapeutically effective amount of plasminogen, as shown by Li, would have also have promoted the formation of mature nerve growth factor (NGF) and/or increased the level of NGF [Claims 1 and 3], with a reasonable expectation of success, because Bruno et al. shows that plasminogen, in coordination with tissue type plasminogen activator (tPA) and plasmin, promotes the conversion of precursor form NGF (proNGF) to mature NGF (mNGF) (MPEP 2143 (I)(G)).
One of ordinary skill in the art would have acknowledged this inherent property of plasminogen, because Bruno et al. teaches that pathological alterations of this cascade in the CNS might cause or contribute to a lack of proper neuronal trophic support in conditions such as cerebral ischemia, seizure and Alzheimer’s disease or, conversely, to excessive local production of neurotrophins as reported in inflammatory arthritis pain (pg. 6735, column 1, Abstract). The deregulation of the protease cascade controlling proNGF conversion and NGF degradation should open new vistas on trophic responses in the adult CNS and in pathological circumstances, such as seizure, cerebral ischemia, and Alzheimer’s disease, where an up-regulation of proNGF is well documented. This pathway might be also of relevance in chronic arthritic pain, where NGF production is a prominent proinflammatory factor (Bruno et al., pg. 6739, column 2, para. 2).
It is noted that the instantly-claimed method for promoting the formation of mature nerve growth factor (NGF) and/or increasing the level of NGF by administering to a subject a therapeutically effective amount of plasminogen is applied to treat subjects who are suffering from, minimally, Alzheimer's disease (instant claim 6, entry #5) (unelected species)).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Li in view of Bruno et al. further addresses the limitations of claims 2, 5-6, 10-11 and 18.
Regarding claim 2, pertaining to the plasminogen promotes cleavage of Pro-NGF to form mature NGF in the nerve tissue of the subject,
Bruno et al. shows that tPA converts plasminogen into the active protease plasmin, which ultimately cleaves proNGF into mNGF (pg. 6736, column 2, lines 6-8). Tissue plasminogen activator and plasminogen are colocalized in neurons (pg. 6735, column 1, Abstract; and pg. 6739, Fig. 7 and legend).
Regarding claim 5, pertaining to the plasminogen has the activities of protecting nerves and promoting nerve regrowth,
Li teaches that GLP-1 regulates various physiological processes of nerve cells, such as cell survival and neuronal axon growth; resists excitability, oxidative damage and death of cultured neurons in vitro; and protects neurons against a variety of apoptotic stimuli and induce differentiation of cultured neural cells in vitro (pg. 4, lines 3-7).
Regarding claim 6, pertaining to the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from a group which includes motor neuron diseases, such as, minimally, primary lateral sclerosis [species election],
Li shows that the disease that is modulated by GLP-1/GLP-1R is one or more diseases selected from a group which includes, minimally, lateral sclerosis and Alzheimer's disease (pg. 5, para. #3).
Regarding claim 10, Li teaches that said plasminogen is used in combination with one or more other drugs or treatment methods (pg. 143, para. 4).
Regarding claim 11, the described invention may be practiced in various ways, for example by intravenous, intraperitoneal, subcutaneous, intracranial, intrathecal, intraarterial (for example via carotid), intramuscular, intranasal, topical or intradermal administration or spinal cord or brain delivery (pg. 26, para. 1).
Regarding claim 18, Li teaches that said plasminogen is selected from the group consisting of Glu-plasminogen, Lys-plasminogen, small plasminogen, micro-plasminogen, delta-plasminogen or their variant that retains plasminogen activity (pg. 143, para. 3).
Claim 4 is rejected under 35 U.S.C. §103 as being unpatentable over Li in view of Bruno et al., as applied to claims 1-3, 5-6, 10-11, and 18 above, and further in view of Pang et al. ( Science, 2005, 306: 487-491).
Li in view of Bruno et al., as applied to claims 1-3, 5-6, 10-11and 18 above, do not show: 1) these neurotrophic factors include brain derived neurotrophic factor (BDNF) [Claim 4].
Regarding claim 4, Pang et al. shows that two secretory proteins, tissue plasminogen activator (tPA) and brain-derived neurotrophic factor (BDNF), have been implicated in the process of long-term memory (pg. 487, columns 1 and 2, Abstract). Although tPA has been implicated in proteolytic degradation of several extracellular matrix proteins, the only well-defined, direct target of tPA is plasminogen. This inactive zymogen is converted to the active form, plasmin, through proteolytic cleavage by tPA (pg. 488, column 1, para. 1). Plasmin is one of the few secreted extracellular proteases that effectively convert precursor proBDNF to mature mBDNF through proteolytic cleavage in vitro (pg. 489, column 2, para. 1).
That is, because Pang et al. shows that proBDNF is converted to mBDNF (the active form of BDNF) by way of the conversion of plasminogen to plasmin via tPA, an increase in the level of plasminogen would increase the level of mBDNF and, therefore, its expression.
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have expected that the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen, as shown by Li in view of Bruno et al., as applied to claims 1-3, 5- 6, 10-11 and 18 above, would have also have promoted the expression and level of one or more neurotrophic factors, including brain-derived neurotrophic factor (BDNF) [Claims 3 and 4], with a reasonable expectation of success, because Pang et al. shows that plasminogen, which is converted to plasmin via tissue plasminogen activator (tPA) converts the inactive precursor form of BDNF (proBDNF) to the active mature form of BDNF (mBDNF) (MPEP 2143 (I)(G)).
Therefore, an increase in the levels of plasminogen resulting from its administration would result in the increase in the level of mBDNF and, therefore, its expression.
One of ordinary skill in the art would have been motivated to acknowledged this inherent property of plasminogen, because Pang et al. teaches that it has long been believed that L-LTP (late phase long-term potentiation with regard to nerve synaptic efficacy) and long-term memory requires new protein synthesis, but the specific product(s) mediating the long-term changes is not known. The described results imply that mBDNF is a key protein synthesis product, if not the only one, needed to carry on all the necessary functions for long-term modification of hippocampal synapses. BDNF elicits long-lasting enhancement of synaptic transmission, promotes dendritic arborization, and stimulates the growth of dendritic spines (pg. 491, column 1, para. 3).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim 9 is rejected under 35 U.S.C. §103 as being unpatentable over Li in view of Bruno et al., as applied to claims 1-3, 5-6, 10-11 and 18 above, and further in view of Gutierrez-Fernandez et al. ( J. Thromb. Haemost. 2007, 5: 1715-1725).
Li in view of Bruno et al., as applied to claims 1-3, 5-6, 10-11 and 18 above, do not explicitly show that: 1) the administered plasminogen increases the plasminogen level in the nerve tissue of the subject [Claim 9].
Regarding claim 9, Gutierrez-Fernandez et al. teaches that studies have documented a requirement for an intact plasminogen (Plg) activation system in
neurite outgrowth induced by nerve growth factor (NGF). Gutierrez-Fernandez et al. shows that NGF treatment increased Plg expression 3-fold and steady state levels of Plg mRNA were increased 6.82-fold (pg. 1715, column 1, Summary, Background & Results).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have expected that the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen, as shown by Li in view of Bruno et al., as applied to claims 1-3, 5-6, 10-11, and 18 above, would have also have increased the level of plasminogen [Claim 9], with a reasonable expectation of success.
Because Gutierrez-Fernandez et al. shows that NGF treatment increases plasminogen expression, and Bruno et al. shows that plasminogen increases the level of mNGF, then one of ordinary skill in the art would have expected that the plasminogen level would increase in a method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen (MPEP 2143 (I)(G)).
That is, a feedback loop related to an increase in plasminogen levels (via administration thereof) resulting in the increase in the level of mNGF resulting in the increase in plasminogen levels would be envisioned.
In addition, even in the absence of Gutierrez-Fernandez et al., it would have been obvious to one of ordinary skill in the art to have expected that plasminogen levels in the nerve tissue of the subject undergoing a method comprising the administration of plasminogen to said subject (MPEP 2144 (I)).
One of ordinary skill in the art would have been motivated to have acknowledged this inherent property of plasminogen, because Gutierrez-Fernandez et al. shows that in the described study, the first evidence that plasminogen (Plg) gene expression is regulated in neuroendocrine cells by a neurotrophin is provided. Because Plg and its activator, t-PA, are expressed in neuronal tissues, particularly within cells of the central nervous system, the response of the Plg gene to a neurotrophin has broad implications for regulation of remodeling of neuroendocrine tissues by increasing the proteolytic activity at local sites within these tissues (pg. 1723, column 1, para. 1). The broad distribution of both Plg and t-PA in neuroendocrine tissues provides a system in which both the activator and substrate zymogen are co-localized. Recent studies document key roles for proteins of the fibrinolytic system in neurite outgrowth and other neuroendocrine functions (pg. 1724, column 1, para. 3).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim 16 is rejected under 35 U.S.C. §103 as being unpatentable over Li in view of Bruno et al., as applied to claims 1-3, 5-6, 10-11, and 18 above, and further as evidenced by NCBI Blast Global Align/ABSS sequence search (SEQ ID NO.: 2; Datasheet [online]. Downloaded on 02 October 2025) .
Li in view of Bruno et al., as applied to claims 1-2, 5-6, 10-11 and 18 above, do not show: 1) the plasminogen comprises the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12.
Regarding claim 16, pertaining to the plasminogen comprises the amino acid sequence represented by SEQ ID NO: 2,
Li as evidenced by NCBI Blast Global Align/ABSS sequence search shows that the instantly-described plasminogen that is represented by SEQ ID NO.: 2 is 100% identical to the plasminogen described by Li that is also represented by SEQ ID NO.: 2.
Li shows that the described plasminogen has at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the sequence 2, 6, 8, 10 or 12 (pg. 10, para. #26; and NCBI Blast Global Align).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have expected that the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen, as shown by Li in view of Bruno et al., as applied to claims 1-3, 5-6, 10-11 and 18 above, could have incorporated a plasminogen, as shown by Li, with the amino acid sequence of SEQ ID NO: 2 [Claim 16], as evidenced by NCBI Blast Global Align/ABSS sequence search, with a reasonable expectation of success, because NCBI Blast Global Align/ABSS sequence search shows that the plasminogen shown by Li (i.e., SEQ ID NO.: 2) is 100% identical to instantly-claimed SEQ ID NO.: 2 (MPEP 2143 (I)(G)).
One of ordinary skill in the art would have been motivated to have made that modification, because one of ordinary skill in the art of promoting NGF in a subject would have preferred to have had a selection of different plasminogen proteins to choose from, depending on the level of efficacy of any given plasminogen protein for the specific disorder being experienced by said subject.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill 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 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.
(1) Claims 1, 2, 6, 10-11, 16 and 18 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 9-11 and 14 of copending Application No. 17/914,265.
The claimed subject matter of instant Application No. 18/037,300 is:
Claim 1. A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 2. the plasminogen promotes cleavage of Pro-NGF to form mature NGF and/or increases NGF expression in the nerve tissue of the subject.
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from the group consisting of:...5) neurodegenerative disease, selected from one or more of the following: Alzheimer's disease...
Claim 10. the plasminogen is administered in combination with one or more drugs or therapies.
Claim 11. the plasminogen is administered intravenously, intramuscularly, or intrathecally, or by nasal inhalation, aerosol inhalation, nasal drop or eye drop.
Claim 16. the plasminogen comprises the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12.
Claim 18. the plasminogen is selected from Glu-plasminogen, Lys-plasminogen, mini-plasminogen, micro-plasminogen, or delta-plasminogen, or a variant thereof retaining the proteolytic activity of plasminogen.
The claimed subject matter of copending Application No. 17/914,265 is:
Claim 1. A method for preventing and treating Alzheimer Alzheimer's disease, comprising administering a therapeutically effective amount of plasminogen to a subject with Alzheimer's disease.
Claim 4. the plasminogen has one or more effects on the subject selected from....promotion of the cleavage of nerve growth factor (NGF) precursor (Pro-NGF).
Claim 9. the plasminogen is selected from Glu-plasminogen, Lys-plasminogen, mini-plasminogen, micro-plasminogen, or delta-plasminogen, or a variant thereof retaining the proteolytic activity of plasminogen.
Claim 10. the plasminogen contains an amino acid sequence shown as sequence 2, 6, 8, 10 or 12.
Claim 11. the plasminogen is used in combination with one or more other treatment methods or drugs.
Claim 14. the plasminogen is administered by nasal inhalation, aerosol inhalation, nasal drops, eye drops, ear drops, an intravenous method,..., an intrathecal method,..., or an intramuscular method.
Although the claims are not identical, they are not patentably distinct from each other because, as demonstrated above in the claim sets from each application, the method for treating Alzheimer's disease comprising administering a therapeutically effective amount of plasminogen, described in copending Application No. 17/914,265 anticipates the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen which treats a subject with Alzheimer's disease, described in instant Application No. 18/037,300.
This is a provisional nonstatutory double patenting rejection because the patentably distinct claims have not been patented.
(2) Claims 1, 3, 4, 6, 9-11, 16 and 18 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 6, 9-11, 15, 16 and 18 of copending Application No. 18/037,299
The claimed subject matter of instant Application No. 18/037,300 is:
Claim 1. A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 3. the plasminogen further increases the expression and level of neurotrophic factors in the nerve tissue of the subject.
Claim 4. the neurotrophic factors include brain-derived neurotrophic factor (BDNF)...
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from the group consisting of:
1) infection, selected from one or more of the following: meningitis, encephalitis, poliomyelitis and epidural abscess;
2) vascular disease, selected from one or more of the following: stroke, transient ischemic attack (TIA), subarachnoid hemorrhage, subdural hemorrhage and hematoma, and epidural hemorrhage;
3) nerve structural damage disease, selected from one or more of the following: brain or spinal cord injury, Bell palsy, cervical spondylosis, carpal tunnel syndrome, brain or spinal cord tumor, peripheral neuropathy and Guillain-Barre syndrome;
4) dysfunction, selected from one or more of the following: headache, epilepsy, insomnia, neuralgia, anxiety and depression;
5) neurodegenerative diseases, selected from one or more of the following: Alzheimer's disease, Parkinson's disease, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinocerebellar ataxia, and Pick disease;
6) motor neuron diseases, selected from one or more of the following: spinal muscular atrophy (SMA), progressive bulbar palsy, progressive muscle atrophy, and primary lateral sclerosis;
7) tumors, selected from one or more of the following: brain tumor and brain cancer.
Claim 9. the plasminogen pathway activator increases plasminogen level in nerve tissue of the subject.
Claim 10. the plasminogen is administered in combination with one or more drugs or therapies.
Claim 11. the plasminogen is administered intravenously, intramuscularly, or intrathecally, or by nasal inhalation, aerosol inhalation, nasal drop or eye drop.
Claim 16. the plasminogen comprises the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12.
Claim 18. the plasminogen is selected from Glu-plasminogen, Lys-plasminogen, mini-plasminogen, micro-plasminogen, or delta-plasminogen, or a variant thereof retaining the proteolytic activity of plasminogen.
The claimed subject matter of copending Application No. 18/037,299 is:
Claim 1. A method for promoting the formation of mature BDNF and/or increasing BDNF level, comprising: administering to a subject a therapeutically effective amount of a plasminogen pathway activator.
Claim 3. the plasminogen pathway activator increases the gene transcription, protein expression and level additional neurotrophic factor in the nerve tissue of the subject.
Claim 4. the additional neurotrophic factor comprises nerve growth factor (NGF).
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from the group consisting of:
1) infection, selected from one or more of the following: meningitis, encephalitis, poliomyelitis and epidural abscess;
2) vascular diseases, selected from one or more of the following: stroke, transient ischemic attack (TIA), subarachnoid hemorrhage, subdural hemorrhage and hematoma, and epidural hemorrhage;
3) nerve structural injury diseases, selected from one or more of the following: brain or spinal cord injury, Bell palsy, cervical spondylosis, carpal tunnel syndrome, brain or spinal cord tumor, peripheral neuropathy and Guillain-Barre syndrome;
4) dysfunction, selected from one or more of the following: headache, epilepsy, insomnia, neuralgia, anxiety and depression;
5) neurodegenerative diseases, selected from one or more of the following: Alzheimer's disease, Parkinson's disease, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinocerebellar ataxia, and Pick disease;
6) motor neuron diseases, selected from one or more of the following: spinal muscular atrophy (SMA), progressive bulbar palsy, progressive muscle atrophy, and primary lateral sclerosis;
7) tumors, selected from one or more of the following: brain tumor and brain cancer.
Claim 9. the plasminogen pathway activator increases plasminogen level in nerve tissue of the subject.
Claim 10. the plasminogen pathway activator is administered in combination with one or more drugs or therapies.
Claim 11. the plasminogen pathway activator is administered by nasal inhalation, aerosol inhalation, nasal drops, eye drops, ear drops, intravenously, intramuscularly, intrathecally, by nasal inhalation, aerosol inhalation, by nasal drop or eye drop.
Claim 15. the plasminogen pathway activator is plasminogen.
Claim 16. the plasminogen comprises the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12.
Claim 18. the plasminogen is selected from Glu-plasminogen, Lys-plasminogen, mini-plasminogen, micro-plasminogen, or delta-plasminogen, or a variant thereof retaining the proteolytic activity of plasminogen.
Although the claims are not identical, they are not patentably distinct from each other because, as demonstrated above in the claim sets from each application, the method for promoting the formation of mature BDNF and/or increasing BDNF level, comprising: administering a therapeutically effective amount of a plasminogen pathway activator which is plasminogen, described in copending Application No. 18/037,299 anticipates the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen which increases BDNF levels and treats the same diseases and disorders, described in instant Application No. 18/037,300.
That is, it appears that plasminogen has the inherent properties of promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, as well as promoting the formation of mature BDNF and/or increasing BDNF level.
This is a provisional nonstatutory double patenting rejection because the patentably distinct claims have not been patented.
(3) Claims 1, 6 and 16 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending Application No. 17/595,113.
The claimed subject matter of instant Application No. 18/037,300 is:
Claim 1. A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from the group consisting of: 5) neurodegenerative diseases, selected from one or more of the following: Alzheimer's disease, Parkinson's disease, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinocerebellar ataxia, and Pick disease.
Claim 16. the plasminogen comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12, and has the proteolytic activity and/or lysine binding activity of plasminogen..
The claimed subject matter of copending Application No. 17/595,113 is:
Claim 16. A method for treating amyotrophic lateral sclerosis (ALS), comprising administering a therapeutically effective amount of a plasminogen pathway activator to a subject suffering from ALS, wherein the plasminogen pathway activator is plasminogen, wherein the plasminogen has (i) an amino acid sequence having at least 80% identity with SEQ ID NO.: 2 and (ii) plasminogen activity comprises delaying muscle atrophy and muscle strength loss.
Although the claims are not identical, they are not patentably distinct from each other because, as demonstrated above in the claim sets from each application, the method for treating ALS, comprising administering a therapeutically effective amount of a plasminogen pathway activator which is plasminogen, described in copending Application No. 17/595,113 anticipates the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen and treats the same diseases and disorders, described in instant Application No. 18/037,300.
This is a provisional nonstatutory double patenting rejection because the patentably distinct claims have not been patented.
(4) Claims 1, 6 and 16 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of copending Application No. 17/793,371.
The claimed subject matter of instant Application No. 18/037,300 is:
Claim 1. A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from the group consisting of: 3) nerve structural damage disease, selected from any one of the following: brain or spinal cord injury, Bell palsy, cervical spondylosis, carpal tunnel syndrome, brain or spinal cord tumor, peripheral neuropathy and Guillain-Barre syndrome.
Claim 16. the plasminogen comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12, and has the proteolytic activity and/or lysine binding activity of plasminogen..
The claimed subject matter of copending Application No. 17/793,371 is:
Claim 1. A method for treating nerve injury in a subject, comprising administering to the subject a therapeutically effective amount of plasminogen, wherein the nerve injury is a spinal cord compression injury.
Claim 12. the plasminogen has at least 90% sequence identity with SEQ ID NO: 2, and has the proteolytic activity of plasminogen.
Although the claims are not identical, they are not patentably distinct from each other because, as demonstrated above in the claim sets from each application, the method for treating nerve injury in a subject, comprising administering to the subject a therapeutically effective amount of plasminogen, described in copending Application No. 17/793,371 anticipates the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen and treats the same diseases and disorders, described in instant Application No. 18/037,300.
This is a provisional nonstatutory double patenting rejection because the patentably distinct claims have not been patented.
(5) Claims 1, 6 and 16 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 of copending Application No. 17/797,504.
The claimed subject matter of instant Application No. 18/037,300 is:
Claim 1. A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from the group consisting of: 5) neurodegenerative diseases, selected from any of the following: Alzheimer's disease, Parkinson's disease, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinocerebellar ataxia and Pick disease.
Claim 16. the plasminogen comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12, and has the proteolytic activity and/or lysine binding activity of plasminogen. .
The claimed subject matter of copending Application No. 17/797,504 is:
Claim 1. A method for treating multiple sclerosis, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 6. the plasminogen has at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with SEQ ID NO: 2, and has the proteolytic activity of plasminogen.
Although the claims are not identical, they are not patentably distinct from each other because, as demonstrated above in the claim sets from each application, the method for treating multiple sclerosis, comprising administering to a subject a therapeutically effective amount of plasminogen, described in copending Application No. 17/797,504 anticipates the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen and treats the same diseases and disorders, described in instant Application No. 18/037,300.
This is a provisional nonstatutory double patenting rejection because the patentably distinct claims have not been patented.
(6) Claims 1, 6 and 16 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of copending Application No. 17/914,275.
The claimed subject matter of instant Application No. 18/037,300 is:
Claim 1. A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or conditions selected from the group consisting of: 5) neurodegenerative diseases, selected from any of the following: Alzheimer's disease, Parkinson's disease, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinocerebellar ataxia and Pick disease.
Claim 16. the plasminogen comprises the amino acid sequence represented by SEQ ID NO.: 2, 6, 8, 10 or 12; or comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with the amino acid sequence represented by SEQ ID NO: 2, 6, 8, 10 or 12, and has the proteolytic activity and/or lysine binding activity of plasminogen. .
The claimed subject matter of copending Application No. 17/914,275 is:
Claim 1. A method for treating Huntingdon's disease, comprising administering a therapeutically effective amount of plasminogen to a subject with Huntingdon's disease, wherein the plasminogen is the only active ingredient for said treatment.
Claim 12. the plasminogen contains an amino acid sequence shown as sequence 2, 6, 8, 10 or 12, or contains a variant of sequence 2, 6, 8, 10 or 12.
Although the claims are not identical, they are not patentably distinct from each other because, as demonstrated above in the claim sets from each application, the method for treating Huntingdon's disease, comprising administering a therapeutically effective amount of plasminogen to a subject, described in copending Application No. 17/914,275 anticipates the method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen and treats the same diseases and disorders, described in instant Application No. 18/037,300.
This is a provisional nonstatutory double patenting rejection because the patentably distinct claims have not been patented.
(7) Claims 1, 6 and 16 are provisionally are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12 of copending Application No. 17/924,617.
The claimed subject matter of instant Application No. 18/037,300 is:
Claim 1. A method for promoting the formation of mature nerve growth factor (NGF) and/or increasing NGF level, comprising administering to a subject a therapeutically effective amount of plasminogen.
Claim 6. the subject is suffering from injury of nerve or brain tissue caused by one or more diseases or c