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 .
Response to Applicant’s Arguments and Amendments
In the response submitted by the Applicant the following 35 U.S.C § 103 (a) rejections are withdrawn:
Claim(s) 1, 2, 9-12, 14-39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber et al. (WO 2013/185032) as supported by STN (L-carnitine)
The Applicant’s amendments limiting the vasoocclusion-inhibiting agent to an anti-P-selectin antibody necessitated the above withdrawals. All arguments drawn to these rejections are now considered moot.
Claim Interpretation
Claims 20-22 are product-by-process limitations nested inside a wherein clauses. M.P.E.P. § 2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.”
“Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).
The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979)
In the immediate case, any means of encapsulation of the vaso-occlusion inhibiting agent into a red blood cell will read on claims 20-22 since the Specification does not provide any clear evidence that any one encapsulation method imparts unique structural properties over the others. In short, are reading on claim 1 will also read on claims 20-22.
Claims 25-30 are intended uses for the composition without providing any additional structural components to the composition. These limitations are not afforded significant patentable weight since the body of the claim fully and intrinsically sets forth all the limitations of the invention (MPEP 2111.02 II).
Since compositions are defined by their components and not by their intended use any composition that contains the ingredients listed in claims will inherently meet the intended uses. Art reading on claim 1 will also read on claims 25-30.
Claim 39 has a wherein clause that limits the result of the method to reduce the size of the occlusion by 10-100%. This reads as an intended result of the method steps. MPEP 2111.04 state:
a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’"
Therefore these limitations are not afforded significant patentable weight and art reading on the method steps of the claim will also read on the intended results since the same steps should obviously yield the same results. However if these results are an unexpected improvement, then this should be pointed out by the Applicant and the claims made commensurate in scope with the results shown. Applicant is encouraged to contact the Examiner if any questions about this arise. In the instant case, art reading on claim 32 will also read on this claim.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 6, 7, and 9-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber et al. (WO 2013/185032) in view of Jin et al. (US 2019/0330181) in light of support by STN Registry entries for Crizanlizumab and L-carnitine.
Ingber et al. teach a composition comprising red blood cells (RBCs) encapsulating compounds including therapeutic agents (Ingber 0082, 00100, 00182). The encapsulation is accomplished with endocytosis with membrane active drugs or ex-vivo electroporation (Ingber, 00100-00102). These therapeutic agents include:
A monoclonal antibody or polyclonal antibody (Ingber, 00124);
Anti-adhesive agent (Ingber, 00147);
Thrombolytic agents including t-PA (tissue plasminogen activator), streptokinase, alteplase, reteplase, and Tenecteplase (Ingber 00138, 00143);
Anti-inflammatory agents including Bosentan (Ingber 00138, 00149);
Inhibitors of RBC aggregation in Sickle Cell Disease;
Anticoagulant agents including hirudin-based thrombin inhibitors (Ingber, 00141, 00144);
Anti-platelet agent (Ingber, 00147)
Modulator of ischemia-reperfusion and oxidative stress including Levocarnitine (Ingber, 00158) also known as L-carnitine as supported by STN Registry; and/or
Agent that counteracts free hemoglobin, heme, or iron including sildenafil (Ingber, 00149).
It would be obvious to encapsulate any combination of these therapeutic agents into the RBCs since these are expressly taught by Ingber et al. as suitable to treat the stenosis caused by blood clotting, stroke, ischemia, inflammation, or sickle cell anemia (Ingber, 00243). The RBCs can be autologous or allogenic (Ingber, 0087). The composition is formulated with a pharmaceutically acceptable carrier or various routes of administrations including subcutaneous, intramuscular, intravenous or epidural injections (Ingber, 00253).
Ingber et al. teach their composition is for treating stenosis caused by blood clotting, stroke, ischemia, inflammation, or sickle cell anemia (Ingber, 00243). The dose can range from 1μg/kg to 150 mg/kg (Ingber, 00279). This dose can be delivered at one time or divided into subdoses daily, weekly for 1 week to 6 months or more (Ingber, 00281). The subject can be a human (Ingber, 00291).
Ingber et al. does not teach the RBCs are loaded with an anti-P-selectin antibody including a monoclonal antibody or Crizanlizumab. However this would be obvious to one of ordinary skill in the art based on the teachings of Jin et al. They teach treating vaso-occlusive diseases including sickle-cell disease with the P-selectin inhibitor Crizanlizumab (Jin, 0078 and 0559), which is a monoclonal antibody as supported by STN Registry (Reg# 1690318-25-2). They also teach the co-administration of the thrombolytic agent Dabigatran (Jin, 0553). It would be obvious to encapsulate Crizanlizumab and Dabigatran into the RBCs of Ingber et al. since these are agents known to treat vaso-occlusive diseases including sickle-cell disease. One of ordinary skill would recognize this as a simply combining components suitable for treating vaso-occlusive diseases including sickle cell (MPEP 2141 III (C-D) and MPEP 2144.06 I).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Applicants Arguments
Applicant's arguments have been fully considered but they are not persuasive.
Applicant argues that combining Ingber et al. with Jin et al. does not render the claims obvious since there is no reasonable expectation of success. However both references are drawn to treating sickle cell disease. Ingber et al teach that antibodies are included in the various therapeutic agents encapsulated into RBCs. Jin et al. expressly teaches P-selectin inhibitors for treating sickle red blood cells (Jin, 0559) these inhibitors include crizanlizumab (Jin, 0560). MPEP 2144.06 I acknowledges it is obvious to combined two compositions when each one is taught as useful for the same purpose. In this case, Ingber et al. and Jin et al. each teach a composition for treating sickle cell disease, therefore it flows logically to encapsulate crizanliaumab into an RBC since encapsulation of therapeutic agents, including antibodies, into RBCs is expressly taught by Ingber et al. Furthermore, one of ordinary skill would recognize this as simply substituting a therapeutic antibody, specific for sickle cell disease, into an RBCs after Ingber et al. expressly teach several antibodies are suitable therapeutic agents to encapsulate. One of ordinary skill would recognize this as an obvious improvement to encapsulate a specific antibody known for treating sickle cell disease into the RBC to make a composition destined to treat this disease. (MPEP 2141 III (C and D)).
Claim(s) 1, 5, and 9-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber et al. (WO 2013/185032) as in view of Pinsky et al. (WO98/13058) as supported by STN Registry (L-carnitine).
Ingber et al. teach a composition comprising red blood cells (RBCs) encapsulating compounds including therapeutic agents (Ingber 0082, 00100, 00182). The encapsulation is accomplished with endocytosis with membrane active drugs or ex-vivo electroporation (Ingber, 00100-00102). These therapeutic agents include:
A monoclonal antibody or polyclonal antibody (Ingber, 00124);
Anti-adhesive agent (Ingber, 00147);
Thrombolytic agents including t-PA (tissue plasminogen activator), streptokinase, alteplase, reteplase, and Tenecteplase (Ingber 00138, 00143);
Anti-inflammatory agents including Bosentan (Ingber 00138, 00149);
Inhibitors of RBC aggregation in Sickle Cell Disease;
Anticoagulant agents including hirudin-based thrombin inhibitors (Ingber, 00141, 00144);
Anti-platelet agent (Ingber, 00147)
Modulator of ischemia-reperfusion and oxidative stress including Levocarnitine (Ingber, 00158) also known as L-carnitine as supported by STN Registry; and/or
Agent that counteracts free hemoglobin, heme, or iron including sildenafil (Ingber, 00149).
It would be obvious to encapsulate any combination of these therapeutic agents into the RBCs since these are expressly taught by Ingber et al. as suitable to treat the stenosis caused by blood clotting, stroke, ischemia, inflammation, or sickle cell anemia (Ingber, 00243). The RBCs can be autologous or allogenic (Ingber, 0087). The composition is formulated with a pharmaceutically acceptable carrier or various routes of administrations including subcutaneous, intramuscular, intravenous or epidural injections (Ingber, 00253).
Ingber et al. teach their composition is for treating stenosis caused by blood clotting, stroke, ischemia, inflammation, or sickle cell anemia (Ingber, 00243). The dose can range from 1μg/kg to 150 mg/kg (Ingber, 00279). This dose can be delivered at one time or divided into subdoses daily, weekly for 1 week to 6 months or more (Ingber, 00281). The subject can be a human (Ingber, 00291).
Ingber et al. does not teach the agent is anti-P-selectin polyclonal antibody (Ingber, 00124). However this would be obvious to one of ordinary skill in the art based on the teachings of Pinsky et al. They teach treating vaso-occlusive diseases including sickle-cell disease with a P-selectin polyclonal antibody (Pinsky, pg. 19, lines 10-15 and 30-35). It would be obvious to encapsulate P-selectin polyclonal antibody into RBCs since they are agents known to treat vaso-occlusive diseases including sickle-cell disease. One of ordinary skill would recognize this as a simply combining components suitable for treating sickle cell disease (MPEP 2141 III (C-D) and MPEP 2144.06 I).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Applicants Arguments
Applicant's arguments have been fully considered but they are not persuasive.
Applicant argues that combining Ingber et al. with Pinsky et al. relies on impermissible hindsight to encapsulate the P-selectin polyclonal antibody into an RBC. Both references are drawn to compositions for treating sickle cell disease. Ingber et al. is clear their composition includes therapeutic agents encapsulated into RBCs. These therapeutic agents include antibodies. Pinsky et al. teach P-selectin polyclonal antibody is a suitable to treat sickle cell disease as well as other ischemic disorders. MPEP 2144.06 I acknowledges it is obvious to combined two compositions when each one is taught as useful for the same purpose. In this case, Ingber et al. and Pinsky et al. each teach a composition for treating sickle cell disease, therefore it flows logically to encapsulate a P-selectin polyclonal antibody into an RBC since encapsulation of therapeutic agents, including antibodies, into RBCs is expressly taught by Ingber et al. Furthermore, one of ordinary skill would recognize this as simply substituting a therapeutic antibody, specific for sickle cell disease, into an RBCs after Ingber et al. expressly teach several antibodies are suitable therapeutic agents to encapsulate. One of ordinary skill would recognize this as an obvious improvement to encapsulate a specific antibody known for treating sickle cell disease into the RBC to make a composition destined to treat this disease. (MPEP 2141 III (C and D)).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
In response to this office action the applicant should specifically point out the support for any amendments made to the disclosure, including the claims (MPEP 714.02 and 2163.06).
CONTACT INFORMATION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THANE E UNDERDAHL whose telephone number is (303) 297-4299. The examiner can normally be reached Monday through Thursday, M-F 8-5 MST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at (571) 272-3311.The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
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