Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-6 and 11-24 are pending.
Priority
Claims 1-6 and 11-24 are a 371 of PCT/CN 2022/144143 filed on December 30, 2022, which has priority to foreign application CHINA 202111675796 filed on December 31, 2021.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on August 14, 2024, was filed before the mailing of the First Office Action on June 13, 2026. The Non-Patent Literature is in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Drawings
The drawings are objected to because:
Figs 2a and 2b are not legible.
Figs 13a and 13b are not legible.
Fig. 26 is not legible.
Fig. 27 is not legible.
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 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 22-24 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.
Claim 22 uses the generic phrase “treating or preventing a hematological disorder” as it relates to administering derived hematopoietic progenitor cells used as a pharmaceutical composition to be administered to a subject. The same generic scope is present in each of the dependent claims, i.e. Claims 23-24.
The specification provides antecedent basis for “treating or preventing a hematological disorder” [¶ 0097].
Applicant’s specification states “the use is use in preparing a medicament for treating and/or preventing a hematological disorder” [¶ 0097]. In paragraph [0098], the specification states the method for treating is administered to a subject in need thereof the hematopoietic progenitor cell or the pharmaceutical composition. In paragraph [0102], the specification states the hematological disorders can be related to cytopathy in blood that include such disorders/diseases as anemia, thrombocytopenia, leukemia, lymphoma, severe aplastic anemia, multiple myeloma, or a combination thereof. However, Applicant’s specification does not provide any other data or disclosure of Applicant’s claimed invention being used to treat any hematological disorders. In order to satisfy written description, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003). Here, Applicant has provided no in vitro or in vivo models, data points, or any other information that would reasonably lead a person of ordinary skill to understand Applicant was in possession of a method for treating hematological disorders in general or the more specific disorders as listed in claim 23. Although the art recognizes that hematopoietic stem/progenitor cells can be used therapeutically in the treatment of hematological diseases such as leukemia, aplastic anemia, and other blood disorders, the specification provides no description, data, working examples, disease models, treatment protocols, or other guidance demonstrating that the claimed hematopoietic progenitor cells are capable of treating or preventing any hematological disorder.
Additionally, claim 22 uses the term “preventing” in the context of administering the pharmaceutical composition of claim 20 for “preventing hematological disorders such as those listed in claim 23. However, the specification is silent as to which subjects would benefit from the treatment, or the appropriate timeline for administering the claimed composition prior to the disease developing. Furthermore, the specification on generically recites “preventing” as it relates to preparing a medicament for treating and/or preventing a hematological disorder. The specification provides no guidance for the appropriate timeline in administering the claimed composition in order to “prevent” a hematological disorder from developing.
Given this and the generic use of “treating or preventing a hematological disorder” as it relates to an Applicant’s claimed derived hematopoietic progenitor cell composition being administered to a subject in need and the absence of teachings that the claimed cell composition is capable of treating and/or preventing any hematological disorder, an Artisan would not understand Applicant to be in possession of the claimed limitations found in claims 20-24.
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.
Claim 23 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 23 recites “the hematological disorder comprises…anemia…severe aplastic anemia”. However, it is unclear whether “anemia” is intended to encompass aplastic anemia, which also includes severe aplastic anemia. Is “anemia” intended as a genus or is “severe aplastic anemia” being treated as separate and distinct from “anemia”. As written, a person of ordinary skill would not understand how the generic “anemia” and all its’ subsets differ from “severe aplastic anemia” for purposes of treatment.
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.
Claims 1-5, 11-12, 13, and 16 are rejected under 35 U.S.C. §102(a)(1) as being anticipated by Chen et al. [CN111607566A, 2020].
Regarding claim 1, Chen et al. teaches a method for preparing hematopoietic progenitor cells [Summary of the Invention], comprising: (1) culturing a pluripotent stem cell to give an embryoid body [Para starting with “In the third aspect of the present invention…(b)”]; (2) subjecting the embryoid body to mesoderm differentiation culture to give a mesodermal cell [Id. Part (c)]; (3) subjecting the mesodermal cell to hemogenic endothelium differentiation culture to give a hemogenic endothelial cell [Id. Part (d)]; and (4) subjecting the hemogenic endothelial cell to hemopoietic progenitor cell differentiation culture to give a hematopoietic progenitor cell [Id. Part (e)], wherein the method prepares hematopoietic progenitor cells in the absence of antibiotics and/or in the absence of monothioglycerol [Specification].
Regarding claim 2, Chen et al. teaches the method according to claim 1, wherein the culture system in step (1) comprises a ROCK inhibitor [Para starting with “In another preferred example, in step (b)”].
Regarding claim 3, Chen et al. teaches the method of claim 1, wherein the culture system in step (2) comprises BMP4 and/or GSK-3β inhibitor [Para starting with “In the third aspect of the present invention…(c)].
Regarding claim 4, Chen et al. teaches the method according to claim 1, wherein the culture system in step (3) comprises at least one selected from the group consisting of: BMP4, vascular endothelial growth factor, fibroblast growth factor, and a TGFβ/ALK inhibitor [Id. Part (d)].
Regarding claim 5, the method according to claim 1, wherein the culture system in step (4) comprises at least one selected from the group consisting of: BMP4, vascular endothelial growth factor, and stem cell factor [Para starting with “In another preferred example, in step (e)”].
Regarding claim 11, Chen et al. teaches a hematopoietic progenitor cell, wherein 90% of the cells have the hematopoietic cell surface antigen CD34+, and the hematopoietic progenitor cell is prepared by the method of claim 1 [Para starting with “In another preferred embodiment, the hematopoietic progenitor cells have any one or more characteristics”].
Regarding claim 12, Chen et al. teaches a hematopoietic progenitor cell, wherein 90% or greater of the cells have the hematopoietic progenitor cell surface antigen CD43+, and the hematopoietic progenitor cell is prepared by the method according to claim 1 [Para starting with “The result is shown in Figure 12. The results showed that the ratio of hematopoietic progenitor cells”].
Regarding claim 13, Chen et al. teaches a hematopoietic progenitor cell, wherein 90% or greater of the cells have the hematopoietic progenitor cell surface antigen CD45+, and the hematopoietic progenitor cell is prepared by the method of claim 1 [Id.].
Regarding claim 16, Chen et al. teaches a hematopoietic progenitor cell, wherein 90% or greater of the cells have the hematopoietic progenitor cell surface antigen combination CD43+/CD45+, and the hematopoietic progenitor cell is prepared by the method of claim 1 [Id.].
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.
Claims 6, 14, 15, and 17-24 are rejected under 35 U.S.C. §103 as being unpatentable over Chen et al. [CN111607566A, 2020], in view of Shimmura et al. [US 2009 047738 A1], in view of Nakajima-Takagi et al. [Role of SOX17 in hematopoietic development from human embryonic stem cells, Blood, 2013], in view of Czechowicz et al. [Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation, Nature Communications, 2019]
Chen et al. discloses each and every limitation found in claims 1-5.
Furthermore, for claim 6, Chen et al. discloses an embryoid body culture system, a mesoderm differentiation culture system, a hemogenic endothelium differentiation culture system, and a hematopoietic progenitor culture system wherein the culture systems are free of antibiotics and/or monothioglycerol [Para starting with “In the third aspect of the present invention”]. However, Chen et al. does not disclose a kit for preparing any of the recited culture limitations.
For the claim 6 limitation combining a kit with the various culture systems, Shimmura et al. discloses a cell culturing kit [¶ 0037]. Furthermore, it is well known that cell cultures, including inducing stem cells, that include culture media, growth factors, supplements, cytokines, reagents, etc. have routinely been marketed and distributed as kits by biotechnology suppliers prior to Applicant’s claimed invention. Given this, it would have been prima facie obvious to a person of ordinary skill prior to the filing of the claimed invention to modify the systems and methods of Chen et al. where it is disclosed a method for culturing hematopoietic progenitor cells derived from human pluripotent stem cells with the further teachings of Shummura et al., as well as known commercially available kits, where a kit for cell culturing was developed. Therefore, there is a reasonable expectation of success that a person of ordinary skill in the art would combine the teachings of Chen et al. with the teachings of Shimmura et al. in order to offer a kit that contained the necessary components for any of the different cell culturing systems listed in claim 6.
For claim 14 where the hematopoietic progenitor cells have a 90% or greater presence of surface antigens CD34+/CD45+, Nakajima-Takagi et al. discloses that hematopoietic progenitor cells derived from pluripotent stem cells include populations that are CD34+/CD45+ during normal differentiation. Nakajima-Takagi et al. further teaches that these surface antigens are a recognized and expected subset of hematopoietic progenitor cell populations used to characterize hematopoietic differentiation in vitro [Abstract]. Furthermore, a person of ordinary skill in the art using routine optimization would easily be able to adjust known culture parameters and/or enrichment techniques that would result in hematopoietic progenitor cell populations with increased proportions of surface antigens such as CD34+/CD45+ where these populations where at least 90% of the cells in these populations display the relevant surface antigens.
For claim 15, the same analysis if applied for surface antigens CD34+/CD43+ as found in the rejection for claim 14.
For claims 17, 18, and 19 where the hematopoietic progenitor cells express CD117 along with CD45, CD34, and CD43, respectively, CD117 (c-Kit) is a well-known surface antigen expressed on hematopoietic stem cells as well as proximal multipotent and oligopotent hematopoietic progenitor populations [See Czechowicz et al. Results ¶ 1]. Furthermore, Nakajima-Takagi et al. further teach that hematopoietic differentiation from pluripotent stem cells proceeds through defined developmental stages characterized by dynamic and overlapping expression of hematopoietic markers that includes CD34, CD43, and CD45 [Abstract and Results]. Given this, a person of ordinary skill in the art would have understood that expression of CD117 together with CD34, CD43, and/or CD45 is expected to be present in hematopoietic progenitor populations depending on the differentiation stage of the cells. Because of this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Chen et al. with the additional teachings of both Nakajima-Takagi et al. and Czechowicz et al. where an artisan would have known based on available teachings that CD117 would have been co-expressed with multiple surface antigens known to be associated with hematopoietic progenitor cells. Because of this, there is a reasonable expectation of success that a person of ordinary skill in the art inducing hematopoietic progenitor cells from pluripotent stem cells using the methods taught by Chen et al. would further be able to further confirm the presence and/or absence of certain cell surface antigens that are known in the art to be present in hematopoietic progenitor cells using known using routine methods such as flow cytometry as taught by both Nakajima-Takagi et al. and Czechowicz et al. Furthermore, a person of ordinary skill in the art using routine optimization would easily be able to adjust known culture parameters and/or enrichment techniques that would result in hematopoietic progenitor cell populations expressing the recited cell surface antigens in the claimed percentages.
For claim 20, Chen et al. discloses a pharmaceutical composition comprised of hematopoietic progenitor cells derived from the methods of claim 1 [Para starting with “In the second aspect of the present invention, there is provided a pharmaceutical composition”], where the certain percentages of cells express the claimed cell surface antigens alone or in combination as claimed in Applicant’s claims 11-19. The same analysis for the §102 and §103 rejections for claims 11-19 are applied here in combination with the teachings of Chen et al. where the derived hematopoietic progenitor cells are incorporated into a pharmaceutical composition. Given this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to utilize known screening methods to determine the presence of certain cell surface markers, i.e. CD34+, CD43+, CD45+, or CD117+ alone or in combination, at the stated percentages using routine optimization through adjusting known culture conditions/parameters to arrive at the claimed limitations already stated in claims 11-19 coupled with the Chen et al. disclosure of combining the derived hematopoietic progenitor cells into a pharmaceutical composition for administration to a subject [Para starting with “In the fifth aspect of the present invention, a method for treating hematological diseases is provided”].
Regarding claim 21 where the pharmaceutical composition can be in a liquid formulation, cell-based formulation, or an intravenous injection, Chen et al. discloses that derived hematopoietic progenitor cells derived from pluripotent stem cells using the methods of claim 1 can be combined into a pharmaceutical composition where it can be in liquid preparation, a cell preparation, or an intravenous injection reagent [Para starting with “In the fifth aspect of the present invention, a method for treating hematological diseases is provided” along with the three subsequent sentences].
For claim 22 where the pharmaceutical composition of claim 20 is administered to a subject in need for treating or preventing hematological disorders, the same analysis that is applied to claim 20 and the preceding claims 11-19 are applied here given that Chen et al. also discloses administering the derived hematopoietic progenitor pharmaceutical composition for the treatment of hematological diseases to a subject in need [Para starting with “In the fifth aspect of the present invention, a method for treating hematological diseases is provided”]. Again, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Chen et al. with the additional teachings of both Nakajima-Takagi et al. and Czechowicz et al. where an artisan would have known based on available teachings that CD117 would have been co-expressed with multiple surface antigens known to be associated with hematopoietic progenitor cells. Because of this, there is a reasonable expectation of success that a person of ordinary skill in the art inducing hematopoietic progenitor cells from pluripotent stem cells using the methods taught by Chen et al. would further be able to further confirm the presence and/or absence of certain cell surface antigens that are known in the art to be present in hematopoietic progenitor cells using known using routine methods such as flow cytometry as taught by both Nakajima-Takagi et al. and Czechowicz et al. Furthermore, a person of ordinary skill in the art using routine optimization would easily be able to adjust known culture parameters and/or enrichment techniques that would result in hematopoietic progenitor cell populations expressing the recited cell surface antigens in the claimed percentages.
For claim 23 where the hematological disorders comprise anemia, thrombocytopenia, leukemia, lymphoma, severe aplastic anemia, multiple myeloma, or a combination thereof, Chen et al. discloses the hematopoietic progenitor cell composition can be used to treat hematological diseases that include same disorders as listed in Applicant’s claim 23 [Para starting with “In the present invention, representative hematological diseases include”].
For claim 24 where a method of treating or preventing a hematological disorder involves administering a derived hematopoietic progenitor cell composition in an effective amount to a subject in need, Chen et al. further defines “effective amount” or “effective dose” as an amount that can produce function or activity on humans and/or animals and can be accepted by humans and/or animals [Para starting with “As used herein, the term “effective amount”].
Given this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods as taught by Chen et al. with the additional teachings of Nakajima-Takagi et al. and Czechowicz et al. where a person of ordinary skill would have known to screen for known cell surface antigens in order to identify the presence of hematopoietic progenitor cells that could be then used in a pharmaceutical composition for administering and treating hematological diseases in a subject in need. Based on this, there is a reasonable expectation of success that an artisan would have been able to produce hematopoietic progenitor cells using the methods of Chen et al. and further confirming the presence of these cells using known screening techniques to determine the presence of known cell surface antigens that are associated with the presence of hematopoietic progenitor cells and further combining these cells with known pharmaceutical carriers in order to produce a pharmaceutical composition that could then be administered to a subject for treating hematological diseases such as anemia and others.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was 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.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN DAVID MOORE whose telephone number is (703)756-1887. The examiner can normally be reached M-F 8-5.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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