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 .
Election/Restrictions
Applicant’s election without traverse of Group IV (claims 20-26) in the reply filed on 6/5/2026 is acknowledged.
Claims 1-19 and 27-35 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 20-26 have been considered on the merits.
Drawings
The drawings are objected to because Figure 1A contains two sequences but there is no associated sequence identifiers, i.e. SEQ ID NOs. It appears that the two sequences are corresponding to SEQ ID NO:2 and 3, however, the drawing should have the SEQ ID NOs.
MPEP2412.04 states that Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing XML" in accordance with paragraph (a) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" or the like in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.832(a) ), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.832(a) ) in the Brief Description is clear.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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 20-26 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 20 discloses the limitation referring to the withdrawn claim 17. It is not clear what the limitation directed to the cell line or organoid of claim 17 is. Applicant is advised to disclose a clear limitation directed to the cell line or organoid rather than referring to the withdrawn claim. For search purpose, the cell line or the organoid is interpreted to be generated with endothelial cells.
The term “high” in claim 20 is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The term “high” limits the “throughput method” in this case, and there is no standard given to determine what the scope of the “high” throughput method would include or exclude.
Claim 20 discloses “restoring” the expression of VWF; VWF-linked protein secretion; and/or VWF string formation. As the claimed method utilizes endothelial cells or organoids thereof derived from hPSCs as discussed above, the term “restoring” would mean that these cells or organoids used in the claimed method would not produce a comparable amount of VWF; sufficient secrete the VWF-linked protein or sufficient string formation. It is not clear if applicant intends to point out that the claimed endothelial cells or organoids thereof are deficient in the production of VWF, secretion of the VWF-linked protein and/or VWF string formation. Clarification is required.
Claim 21 discloses the term “the cell culture” in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 22 discloses the term “VWF-linked protein secretion”. The scope of “VWF-linked protein” is not clear. The specification does not provide any definition or description with regard to the scope of this term or what kind of proteins would be included as “VWF-linked protein”. The instant specification fails to provide what the VWF-linked protein would be. Under the broadest reasonable interpretation, the “VWF-linked protein” could be interpreted as any protein physically attached to VWF (VWF-binding protein) or any protein functionally associated with VWF, e.g. those involved in a clotting mechanism. The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds". See, e.g., the following decisions: In re Hammack, 427 F 2d. 1378, 1382, 166 USPQ 204, 208 (CCPA 1970); In re Venezia 530 F 2d. 956, 958, 189 USPQ 149, 151 (CCPA 1976); In re Goffe, 526 F 2d. 1393, 1397, 188 USPQ 131, 135 (CCPA 1975); In re Watson, 517 F 2d. 465, 477, 186 USPQ 11, 20 (CCPA 1975); In re Knowlton 481 F 2d. 1357, 1366, 178 USPQ 486, 492 (CCPA 1973).
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 20-26 are 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a high throughput method for identifying a therapeutic agent for treating a bleeding disorder by contacting a candidate agent with endothelial cells or organoids produced with the endothelial cells. Considering the instant claims are dependent on the withdrawn claim 17 which appears to be directed to endothelial cells derived from human pluripotent stem cells (hPSCs), the endothelial cells or organoids disclosed in the instant claims are interpreted as those derived from hPSCs.
The claims disclose that any agent that is effective in (i)-(iv) disclosed in claim 20 would be identified as a therapeutic agent effective for treating bleeding disorders.
The scope of “bleeding disorder” is broad encompassing acquired bleeding disorders such as disseminated intravascular coagulation (DIC), liver disease-associated bleeding, vitamin K deficiency bleeding, von Willebrand disease, hemophilia (A and B), and platelet disorders (deficiency or problem in clotting factors) according to Bleeding Disorders: Types (2023, NHLBI, NIH). It is understood that “bleeding disorder” is due to the inability to form effective blood clots.
Claim 20, however, does not limit the type of the bleeding disorders, and yet discloses that the agent effective in enhancing the expression of vWF level; VWF secretion; VWF string formation would be therapeutic for ANY bleeding disorder.
The specification is indeed limited to von Willebrand disease and the use of the endothelial cells as claimed for a method of high throughput assay to identify to treat von Willebrand disorder.
It is also noted that claim 26 discloses that the bleeding disorder includes thrombosis, deep vein thrombosis, blood clots, stroke, heart disease and von Willebrand disease. As the “bleeding disorder” is understood as inability to form effective blood clots, the diseases/conditions related to blood clot formation would not be considered as “bleeding disorder”. According to the instant specification, thrombosis, deep vein thrombosis, blood clots, stroke, heart disease and von Willebrand disease are considered as “blood disorder” (para. 13). It is construed that stroke or heart disease is not generally considered as a bleeding disorder, although stroke is caused by bleeding in brain.
Even if the claimed diseases are considered as bleeding disorders, however, the specification fails to provide any disclosure that the agents effective in (i) enhancing the expression levels of VWF; (ii) restoring the expression of VWF; (iii) restoring VWF-linked protein secretion, and/or (iv) restoring VWF string formation as claimed would necessarily and sufficiently treat those diseases including thrombosis, deep vein thrombosis, blood clots, stroke, or heart disease other than von Willebrand disease.
M.P.E.P. §2163 recites, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus…when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.”
Applicant is advised to amend the claims to limit the “bleeding disorder” to von Willebrand disease.
Claim 21 discloses “a genetic agent”, “component of the cell culture” or “a small molecule” being the therapeutic agent. The scope of “a genetic agent”, “component of the cell culture” or “a small molecule” is extremely broad and the specification does not provide sufficient representative number of species belonging to the genus as claimed.
For the “genetic agent”, the term is defined as polynucleotides and analogs thereof (para. 75), and the specification provides an example of the genetic agent as a therapeutic agent which is a polynucleotide encoding VWF protein or a polynucleotide encoding a protein linked/associated with VWF secretion. While von Willebrand disease would be corrected by a gene therapy expressing VWF protein, however, the “protein linked/associated with VWF secretion” is not disclosed what these proteins would be. The specification failed to provide any species belonging to the genus of “protein linked/associated with VWF secretion”.
Regarding the “component of the cell culture”, the claim does not particularly define what the term intends to point out, and thus, the scope of the term is extremely broad to encompass any molecules present in any cell culture including but not limiting cell culture medium and supplements, cells and any molecules produced by the cells, etc. There is no clear disclosure in the instant specification what the scope of the term is. Rather, the specification merely discloses a single example of the component of the cell culture being “blood plasma” (para. 16), and Fig. 8 shows that blood plasma increases VWF levels in hPSC-EC. There is no other example or embodiment supporting any other “component of the cell culture” for the therapeutic agent.
Claim 22 discloses the term “derivative” of a polynucleotide encoding VWF protein or a protein linked/associated with VWF secretion.
The specification, however, does not contain an adequate description for the entire scope of this limitation and thus the claims. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 20-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception, i.e. abstract idea, without significantly more. The claim(s) recite(s) a method of identifying a therapeutic agent for treating a bleeding disorder comprising a step of contacting a plurality of candidate agents with an endothelial cell line or endothelial cell organoid wherein the endothelial cells lack VWF expression. While the claims do not particularly disclose a step of identifying the agent, the method is directed to identifying the agent based on the capability of the tested agent for enhancing the expression levels of VWF, restoring the expression of VWF, restoring VWF-linked protein secretion or restoring VWF string formation. Thus, the step of identifying the therapeutic agent based on the results of the contacting step is required for the claimed method. This identifying step is considered to be carried out by a mental process which does not require an active step to be carried out. Thus, the claims are directed to an abstract idea. It is noted that the use of endothelial cells lacking VWF in the method analyzing the effect of vWF is known in the art according to Randi et al. (EP3488858A1) (Step 2A prong one: YES).
This judicial exception is not integrated into a practical application because the claims do not disclose any additional elements to integrate the judicial exception into a practical application. This judicial exception is not integrated into a practical application because the additional element, i.e. step of contacting the endothelial cell line or endothelial organoids does not provide any improvement to a technology or technical field, or applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. Rather the additional element is directed to a merely extra-solution activity to obtain the data to carry out the judicial exception of comparing the data (see MPEP2106.04(d)(2)). Rather the additional element is directed to a merely extra-solution activity to obtain the data to carry out the judicial exception of comparing the data. The claims disclose intended purpose of “for treating a bleeding disorder”. However, there is no active step of carrying out the intended purpose. MPEP2106.04(d)(2) states that if the limitation does not actually provide a treatment or prophylaxis, e.g., it is merely an intended use of the claimed invention or a field of use limitation, then it cannot integrate a judicial exception under the "treatment or prophylaxis" consideration (STEP 2A, Prong Two: NO).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there is no additional element that amount more than the judicial exception. The additional element of the contacting step cannot be considered to provide any inventive concept significantly more than the judicial exception (STEP 2B: NO).
The dependent claims 21-24 and 26 do not provide any other active step but further limiting the types of agents being screened or type of bleeding disorder.
Claim 25 discloses a further step of assessing toxicity and/or pharmacokinetics of the therapeutic agent. The step of “assessing” is also considered an abstract idea that can be carried out mentally based on the screening data and/or additional testing which would be also considered as an extra-solution activity. Thus, this additional step does not integrate the judicial exception to a practical application or add significantly more than the judicial exception.
Based on the above discussion, the claimed method are considered directed to a judicial exception and thus, the claims do not disclose an eligible subject matter under the 101.
Claim Rejections - 35 USC § 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 (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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 20-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Randi et al. (EP3488858A1; published on 5/29/2019) in view of Boer et al. (2019, HemaSphere).
Claim 20 is interpreted as a high throughput method for identifying a therapeutic agent for treating a bleeding disorder by contacting a plurality of candidate agents with endothelial cell lacking VWF or an organoid thereof. As the limitation directed to the cell line or the organoid of claim 17 is the withdrawn claims but not clearly disclosed in claim 20, the limitation is interpreted broadly as an endothelial cells lacking VWF expression.
Randi et al. teach a method utilizing vWF-deficient endothelial cells to determine the effect in inhibiting the angiogenesis in the endothelial cells (para. 9), and a composition comprising vWF (para. 11). Randi et al. also teach that the von Willebrand factor composition can be obtained from plasma or by expression in cell culture (para. 41). The vWF-deficient endothelial cells are produced by transfecting HUVECs with siRNA specific for vWF (para. 49).
Randi et al. do not teach a high throughput assay for identifying a therapeutic agent by contacting the vWF-deficient endothelial cells with a plurality of candidate agents.
Boer et al. teach von Willebrand disease model includes cell models utilizing endothelial cells which can be used in high throughput screening assays (see Table 1).
It would have been obvious to a person skilled in the art to use vWF-deficient endothelial cells as a model for von Willebrand disease (vWD) model in a high throughput screening assay taught by Boer et al. with a reasonable expectation of success. A person of ordinary skilled in the art would have been motivated to do so because vWD is characterized by quantitative (type 1 and 3) or qualitative (type 2) defects of VWF, and the severe quantitative VWF deficiency is seen in type 3 vWD is usually caused by genetic defects in the VWF gene according to Boer et al. (see p.1-2). Thus, one skilled in the art would recognize that the vWF-deficient endothelial cells taught by Randi et al. would mimic the deficiency in VWF in vWD, and thus, it is reasonable to use them for screening a therapeutic agent for treating a disease related to the VWF deficiency in vWD.
The wherein clause of claim 20 is directed to the agents that produce the claimed effects (i)-(iv) is identified as effective for the bleeding disorders. The limitation implies a step of determining the effects being a prerequisite to the step of identifying the candidate agent as a therapeutic agent. However, the determining step is not disclosed as a required active step for the claimed method. Thus, the wherein clause does not provide any patentable weight in determining the claimed method of identifying a therapeutic agent.
Even if the wherein clause of claim 20 requires to assay the production of VWF or VWF-linked protein secretion, etc. after the contacting step, Boer et al. teach that a cell morphology (HUVECs from inherited VWD), VWF production, storage, secretion and activity levels, multimerization patterns, factor VIII production and platelet binding (p.3, 1st col.). Thus, it would have been obvious to carry out an assay to determine the effect of candidate agents for VWF production and/or secretion in the vWF-deficient endothelial cells with a reasonable expectation of success.
Regarding the step of identifying the agent effective in producing the claimed effect as the therapeutic agent effective for treating bleeding disorders, it is considered that the screening method does not require to positively identify an agent being a therapeutic agent. In other words, not all of the candidate agents would produce the claimed effect. Therefore, the identifying step would be considered contingent to the candidate agent. After the determining the effect, those agents that do not produce the claimed effect are not identified as a therapeutic agents. Thus, the step of identifying a therapeutic agent for treating a bleeding disorder is not required for the claimed method (see MPEP2111.04(II)).
Regarding claims 21-24, the wherein clauses of these claims are directed to the step of identifying the candidate agents as therapeutic agent producing the effects (i)-(iv), and the types of therapeutic agents. As discussed above, this identifying step is a contingent limitation that is not required for the claimed method. Therefore, the limitations of claims 21-24 are not required for the claimed method of claim 20.
Regarding claim 25 directed to the additional step of assessing toxicity or pharmacokinetics of the therapeutic agent, this limitation requires the identification of a therapeutic agent. As discussed above, the identifying step is contingent upon the claimed effect, thus, this additional step would be also considered as contingent as it is directed to the contingent limitation.
Regarding claim 26, Randi et al. in view of Boer et al. is directed to the treating vWD, and thus, the combined teachings meet the limitation.
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.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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, JAMES SCHULTZ can be reached at 571-272-0763. 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.
/TAEYOON KIM/ Primary Examiner, Art Unit 1631
Prosecution Insights