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 .
Priority
This application is a CIP of 16/966,747 filed 07/31/2020 now abandoned. 16/966,747 is a 371 of PCT/EP2019/052542 filed 02/01/2019 which claims the benefit of the priority of European Patent Application No. EP 18186061.0 filed 07/27/2018. PCT/EP2019/052542 has PRO 62/624,997 filed 02/01/2018,
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements submitted on 12/22/2023 been considered by the examiner.
Claim Status
Claims 1-14 are being examined on the merits in this office action.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the use of the instant polypeptide of SEQ ID NO: 1 for inhibiting thrombus formation, inhibiting platelet recruitment, neutrophil recruitment, or neutrophil extracellular trap formation (NETosis) in a subject, does not reasonably provide enablement for the use of the instant polypeptide of SEQ ID NO: 1 for treating and preventing thromboinflammation such as aneurysms, skeletal muscle ischemia-reperfusion syndrome, atherosclerosis, plaque rupture, thrombus formation following cerebral injuries, coronary artery disease, acute myocardial infraction, cancer-associated thrombosis, metastasis-associated thrombosis, stroke-associated thrombosis, Behçet’s disease (BD), antineutrophil cytoplasmic antibody-associated (ANCA) vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus erythematosus etc. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1561 (Fed. Cir., 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558,1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547, the court recited eight factors to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
1) the quantity of experimentation necessary
2) the amount of direction or guidance provided
3) the presence or absence of working examples
4) the nature of the invention
5) the state of the art
6) the relative skill of those in the art
7) the predictability of the art
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099,1108,427 F.2d 833, 839,166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The breadth of the claims and the nature of the invention
The invention is drawn to a method of treating and/or preventing thromboinflammation in a subject, comprising administering to said subject a therapeutically effective amount of a protein or polypeptide with the amino acid sequence SEQ ID NO: 2, wherein said thromboinflammation is selected from the group comprising atherosclerosis, plaque rupture, devices-induced thromboinflammation, thrombosis induced by catheterism and/or stent positioning procedures, thrombosis induced by extracorporeal circulation, thrombus formation following cerebral injuries, coronary artery disease, acute myocardial infraction, cancer-associated thrombosis, metastasis-associated thrombosis, stroke-associated thrombosis, Behçet’s disease (BD), antineutrophil cytoplasmic antibody-associated (ANCA) vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, familial Mediterranean fever, thromboangiitis obliterans (TAO), sepsis, inflammatory bowel diseases, heparin-induced thrombocytopenia, immunothrombosis, thrombosis associated with preeclampsia, thrombotic complication in cell and cell cluster transplantation and in whole organ transplantation or grafts, venous thromboembolism, aneurysms, and skeletal muscle ischemia-reperfusion syndrome. Examiner notes that Applicant is claiming a method that treats and prevents the recited conditions such as aneurysms, coronary artery disease, acute myocardial infraction.
Additionally, the term “preventing” is a potent and absolute term indicating that the method of prevention will necessarily prevent the onset of all the conditions recited in the instant claim 5. Further, the instant claims define “treatment” as therapeutic treatment, prophylactic or preventative measures wherein the objective is to prevent the disease or condition associated with the recruitment of neutrophils, the activation of neutrophils or to the extrinsic coagulation pathway (Instant Specification page 13).
The term “preventing” encompasses a wide range of situations, from preventing a disease from occurring to preventing it from progressing, and in addition, the term is not limited by any time frame.
The applicant is claiming a “method of preventing”. Prevention, as defined by Merriam-Webster dictionary, is to keep from happening or existing, which implies taking advance measure against something possible or probable. In addition, preventing embraces complete 100% inhibition. Therefore, the evidence of 100% prevention would be more challenging to obtain than the evidence of treatment since one would have to show that the administration of the polypeptide would never develop any of the conditions recited in the instant claims such as aneurysms.
The instant specification is bereft of evidence of prevention of any of the conditions recited in the instant claims such as aneurysms. Since absolute success in preventing conditions such as aneurysms is not reasonably possible based on the state of the art at the earliest effective filing date of the instant application, the specification, which lacks an objective showing that all the conditions recited in claim 5 can actually be treated or prevented, is viewed as lacking.
The claims are thus broad insofar as to suggest that the claimed polypeptide of SEQ ID NO: 1 or 2 can treat and prevent all the conditions recited in claim 5.
The state of the prior art and the level of predictability in the art and the relative skill of those in the art
The state of the art is such that there is evidence and established literature about the challenges of treating or preventing aneurysms. Gao et al. (Signal Transduction and Targeted Therapy (2023) 8:55) teaches there is no effective drug for the prevention or treatment of aneurysms (Page 11, right col., last paragraph).
Given that there is no evidence in the art of a compound that has been found to generally treat or prevent the conditions recited such as aneurysms, the treatment of prevention of the conditions recited in the instant is not considered enabled.
One of ordinary skill in the art would not be able to use the instant polypeptide to prevent all the conditions recited in the instant claims generally and achieve a reasonable level of success in doing so due to the absence in the art of a compound that is able to treat and prevent aneurysms. It is well established that a utility rejection is therefore proper when the scope of enablement is not reasonably correlated to the scope of the claim.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)”. The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.”
The instant disclosure is focused on the use of the instant polypeptide for inhibiting thrombus formation, inhibiting platelet recruitment, neutrophil recruitment, or neutrophil extracellular trap formation (NETosis) in a subject.
See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.).
As a result, the specification needs to have more details on how to make and use the invention in order to be enabling. The relative skill of those in the art is high. However, the art of treating all the conditions recited is highly unpredictable.
The examiner cites Gao et al. (Signal Transduction and Targeted Therapy (2023) 8:55) as an evidentiary references to illustrate the state of the art.
Gao teaches there is no effective drug for the prevention or treatment of aneurysms (Page 11, right col., last paragraph).
These teachings show how unpredictable the treatment or prevention of aneurysm is. In light of the state of the prior art, it is apparent that the instantly claimed polypeptide is not capable of use to treat and prevent all conditions recited in the instant claim 5.
The amount of direction or guidance provided and the presence or absence of working examples
The claims are drawn to the use of the instant polypeptide of SEQ ID NO: 1 for treating and preventing thromboinflammation such as aneurysms, skeletal muscle ischemia-reperfusion syndrome, atherosclerosis, plaque rupture, thrombus formation following cerebral injuries, coronary artery disease, acute myocardial infraction, cancer-associated thrombosis, metastasis-associated thrombosis, stroke-associated thrombosis, Behçet’s disease (BD), antineutrophil cytoplasmic antibody-associated (ANCA) vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus erythematosus etc.
The instant specification discloses the use of the instant polypeptide of SEQ ID NO: 1 for inhibiting thrombus formation, inhibiting platelet recruitment, neutrophil recruitment, or neutrophil extracellular trap formation (NETosis) in a subject (Fig. 1-20). The instant specification does not include other examples showing effect of the claimed polypeptide on treating and preventing all the conditions recited in claim 5.
The quantity of experimentation necessary
Given the well-known unpredictability of the art as well the incomplete experimental evidence commensurate in scope with the claims, the skilled artisan would not be able to agree that the claimed polypeptide can treat and prevent all the conditions recited in claim 5 such as atherosclerosis, plaque rupture, devices-induced thromboinflammation, thrombosis induced by catheterism and/or stent positioning procedures, thrombosis induced by extracorporeal circulation, thrombus formation following cerebral injuries, coronary artery disease, acute myocardial infraction, cancer-associated thrombosis, metastasis-associated thrombosis, stroke-associated thrombosis, Behçet’s disease (BD), antineutrophil cytoplasmic antibody-associated (ANCA) vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, familial Mediterranean fever, thromboangiitis obliterans (TAO), sepsis, inflammatory bowel diseases, heparin-induced thrombocytopenia, immunothrombosis, thrombosis associated with preeclampsia, thrombotic complication in cell and cell cluster transplantation and in whole organ transplantation or grafts, venous thromboembolism, aneurysms, and skeletal muscle ischemia-reperfusion syndrome.
In order to determine if the claimed polypeptide would treat and prevent all the conditions recited in claim 5, the suitable dosage as well as clinical trials or assays that can correlate to clinical efficacy of such treatment would be needed. This is undue experimentation given the limited guidance and experimentation provided by the applicant.
In view of the Wands factors discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in unduly burdensome experimentation to assess whether administration of the claimed polypeptide would treat and prevent all the conditions recited in claim 5. Thus, the rejection of these claims under 35 USC 112(a) is proper.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim Interpretation
The instant claims recite treating and/or preventing thromboinflammation. The instant specification defines that thromboinflammation is selected from the diseases recited in claim 5 and that thromboinflammation is thrombosis induced by catheterism and/or stent positioning procedures at the site of local vascular stenosis (Page 6, line 16-28; Page 7, line 1-5).
Examiner notes that a reference that teaches the use of the instant polypeptide to treat thrombosis in the recited conditions would read on the instant claims.
Claims 1-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Godfroid et al. (US20160046728A1 – hereinafter Godfroid”).
Regarding claim 1, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is at least 98% identical to the instant SEQ ID NO: 2 (See Fig. 3B; [0007-0013]). Godfroid further teaches a method of treating conditions comprising administering the polypeptide of SEQ ID NO:36, wherein the condition is selected from the group comprising deep vein thrombosis, portal vein thrombosis, jugular vein thrombosis, renal vein thrombosis, pulmonary embolism, unstable angina, acute coronary syndrome, myocardial infraction, cerebral ischemia and stroke or the thrombus formation during and/or after a medical procedure such as comprising extracorporeal membrane oxygenation for blood oxygenation, extracorporeal circulation during cardiopulmonary bypass, dialysis and extracorporeal filtration of blood, percutaneous angioplasty, use intraluminal catheters and stents, intra-aortic balloon pump [0015-0018]. Godfroid teaches that the polypeptide for use for preventing and/or treating thrombosus or thrombus formation in cerebral ischemia [0073, 0169-0171, 0187, 0199, 0207]. Godfroid teaches a composition or pharmaceutical composition or medicament comprising the polypeptide and at least one pharmaceutically acceptable excipient [0074-0075] and a method of treating a plasma contact factor-related disease of the invention is selected from the group comprising deep vein thrombosis, portal vein thrombosis, jugular vein thrombosis, renal vein thrombosis, pulmonary embolism, unstable angina, acute coronary syndrome, myocardial infraction, cerebral ischemia, and stroke [0077-0081]. Examiner notes that Godfried teaches some of the conditions that the instant invention defines as thromboinflammation such as thrombus formation during and/or after a medical procedure such as comprising extracorporeal membrane oxygenation for blood oxygenation, extracorporeal circulation during cardiopulmonary bypass, dialysis and extracorporeal filtration of blood, percutaneous angioplasty, use intraluminal catheters and stents, intra-aortic balloon pump, acute coronary syndrome, myocardial infraction, cerebral ischemia and stroke. The teachings of Godfroid anticipate the instant claims.
Regarding claim 2, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is at least 98% identical to the instant SEQ ID NO: 2 (See Fig. 3B; [0007-0013]). The difference between the sequence of Godfroid and instant claims is the amino acid at position 54 (see below query match)
PNG
media_image1.png
243
982
media_image1.png
Greyscale
However, Godfried teaches that conservative amino acid substitutions wherein the instant Gln (N) can be substituted with Asn (N) [0091]. Thus, the sequence of Godfroid reads on comprising SEQ ID NO: 2.
Regarding claim 3, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is 100% identical to the instant SEQ ID NO: 1 (See Fig. 3B; [0007-0013]; see query below).
PNG
media_image2.png
356
1035
media_image2.png
Greyscale
Regarding claim 4, Godfroid teaches that the polypeptide binds to activated Factor XIa, fXIIa, Kallikrein [0064-0065, 0185-0186, 0197].
Regarding claims 5 and 7, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is at least 98% identical to the instant SEQ ID NO: 2 (See Fig. 3B; [0007-0013]). Godfroid further teaches a method of treating conditions comprising administering the polypeptide of SEQ ID NO:36, wherein the condition is selected from the group comprising deep vein thrombosis, portal vein thrombosis, jugular vein thrombosis, renal vein thrombosis, pulmonary embolism, unstable angina, acute coronary syndrome, myocardial infraction, cerebral ischemia and stroke or the thrombus formation during and/or after a medical procedure such as comprising extracorporeal membrane oxygenation for blood oxygenation, extracorporeal circulation during cardiopulmonary bypass, dialysis and extracorporeal filtration of blood, percutaneous angioplasty, use intraluminal catheters and stents, intra-aortic balloon pump [0015-0018]. Godfroid teaches that the polypeptide for use for preventing and/or treating thrombosus [0073, 0080, 0169-0171, 0187, 0199, 0207].
Regarding claim 6, Godfroid teaches a polypeptide treated thrombus formation [0073, 0080, 0169-0171, 0187, 0199, 0207], such as in cerebral ischemia [0199].
Regarding claim 8, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is at least 98% identical to the instant SEQ ID NO: 2 (See Fig. 3B; [0007-0013]). Godfroid further teaches a method of treating conditions comprising administering the polypeptide of SEQ ID NO:36, wherein the condition is selected from the group comprising deep vein thrombosis, portal vein thrombosis, jugular vein thrombosis, renal vein thrombosis, pulmonary embolism, unstable angina, acute coronary syndrome, myocardial infraction, cerebral ischemia and stroke or the thrombus formation during and/or after a medical procedure such as comprising extracorporeal membrane oxygenation for blood oxygenation, extracorporeal circulation during cardiopulmonary bypass, dialysis and extracorporeal filtration of blood, percutaneous angioplasty, use intraluminal catheters and stents, intra-aortic balloon pump [0015-0018]. Godfroid teaches that the polypeptide for use for preventing and/or treating thrombosus [0073, 0169-0171, 0187, 0199, 0207]. Godfroid teaches a composition or pharmaceutical composition or medicament comprising the polypeptide and at least one pharmaceutically acceptable excipient [0074-0075] and a method of treating a plasma contact factor-related disease of the invention is selected from the group comprising deep vein thrombosis, portal vein thrombosis, jugular vein thrombosis, renal vein thrombosis, pulmonary embolism, unstable angina, acute coronary syndrome, myocardial infraction, cerebral ischemia, and stroke [0077-0081]. Examiner notes that Godfried teaches some of the conditions that the instant invention defines as thromboinflammation such as thrombus formation during and/or after a medical procedure such as comprising extracorporeal membrane oxygenation for blood oxygenation, extracorporeal circulation during cardiopulmonary bypass, dialysis and extracorporeal filtration of blood, percutaneous angioplasty, use intraluminal catheters and stents, intra-aortic balloon pump, acute coronary syndrome, myocardial infraction, cerebral ischemia and stroke.
Regarding claim 9, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is at least 98% identical to the instant SEQ ID NO: 2 (See Fig. 3B; [0007-0013]). The difference between the sequence of Godfroid and instant claims is the amino acid at position 54 (see below query match)
PNG
media_image1.png
243
982
media_image1.png
Greyscale
However, Godfried teaches that conservative amino acid substitutions wherein the instant Gln (N) can be substituted with Asn (N) [0091]. Thus, the sequence of Godfroid reads on comprising SEQ ID NO: 2.
Regarding claim 10, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is 100% identical to the instant SEQ ID NO: 1 (See Fig. 3B; [0007-0013]; see query below).
PNG
media_image2.png
356
1035
media_image2.png
Greyscale
Regarding claim 11, Godfroid teaches that the polypeptide binds to activated Factor XIa, fXIIa, Kallikrein [0064-0065, 0185-0186, 0197].
Regarding claims 12 and 14, Godfroid teaches a polypeptide of SEQ ID NO: 36 which is at least 98% identical to the instant SEQ ID NO: 2 (See Fig. 3B; [0007-0013]). Godfroid further teaches a method of treating conditions comprising administering the polypeptide of SEQ ID NO:36, wherein the condition is selected from the group comprising deep vein thrombosis, portal vein thrombosis, jugular vein thrombosis, renal vein thrombosis, pulmonary embolism, unstable angina, acute coronary syndrome, myocardial infraction, cerebral ischemia and stroke or the thrombus formation during and/or after a medical procedure such as comprising extracorporeal membrane oxygenation for blood oxygenation, extracorporeal circulation during cardiopulmonary bypass, dialysis and extracorporeal filtration of blood, percutaneous angioplasty, use intraluminal catheters and stents, intra-aortic balloon pump [0015-0018]. Godfroid teaches that the polypeptide for use for preventing and/or treating thrombosus [0073, 0080, 0169-0171, 0187, 0199, 0207].
Regarding claim 13, Godfroid teaches a polypeptide treated thrombus formation [0073, 0080, 0169-0171, 0187, 0199, 0207], such as in cerebral ischemia [0199].
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MERCY H SABILA/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654
Prosecution Insights