DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Restriction/Election
Applicant's election with traverse of Invention I (Claims 1-14), CD44 (Species I--Type of Expression Marker), ACTB (Species II-Type of Protein), ACTS (Species III—Protein Not Expressed), and BMP-7 (Growth Factor) in the reply filed on August 6, 2026 is acknowledged. The traversal is on the ground that that preparation method of claim 15 (Invention II) inevitably produces the thawed human mesenchymal stem cells used to practice the treatment methods of claims 1-14. This is not found persuasive because the cells can be used for other purposes besides treating sepsis. For example, the mesenchymal stem cells manufactured in Group II can be used to cure skin injuries. There would be a serious search burden placed on examiner because each invention requires a distinct search which is not coextensive with the search of the other invention. The requirement is still deemed proper and is therefore made FINAL. Claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on August 6, 2026.
Claim Objections
Claim 8 is objected to because “in in vivo” should be –in-vivo--.
Claim 10 is objected to because of the following informalities: In claim 10, line 2, “VEGF seric concentration” should be changed to –VEGF concentration--. Appropriate correction is required.
Claim 11 is objected to because “having been subject to an intake of tobacco” should be –not having been subject to an intake of tobacco--.
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 a method of treating sepsis in a subject in need thereof comprising administering to said subject thawed human mesenchymal stem cells (MSC) from Wharton’s jelly, wherein intravenous, intravascular, intracerebral, parenteral, intraperitoneal, epidural, intra-spinal, intrastemal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, or intramuscular administration routes are used, does not reasonably provide enablement for a method of treating sepsis in a subject in need thereof comprising administering to said subject thawed human mesenchymal stem cells (MSC) from Wharton’s jelly. 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.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc. 8 USPQD2d 1217 (Fed. Cir. 1988). Whether undue experimentation is required is a conclusion reached by weighing several factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQQ2d 1400 (Fed. Cir. 1988)
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experiment to make and use the invention based on the content of the disclosure is undue.
Nature of the Invention:
The invention is a method for administering thawed human mesenchymal stem cells from Wharton’s jelly to treat sepsis.
Breadth of the Claims: The breadth of the claims are so broad that they encompass any method of administration including a topical administration method of the thawed mesenchymal stem cells onto skin to treat sepsis.
Teachings from the Prior Art:
Chao teaches a method of intravenous administration (Page 3, Administration of MSCs after CLP).
Applicants Specification/Guidance/Working Examples
Page 28 bridging page 29 of applicants’ specification states that the thawed mesenchymal stem cells can be administered to the patient by “intravenous, intravascular, intracerebral, parenteral, intraperitoneal, epidural, intra-spinal, intrastemal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, or intramuscular routes. The reference does not teach other forms of administration such as oral/gastrointestinal, intranasal, and/or topical.
Page 42 of the specification states that the clinical cells that are prepared are administered to septic shock patients via a central venous route after thawing and washing of the mesenchymal stem cells.
Conclusion:
Both the prior art and applicants’ specification teach thawed mesenchymal stem cell administration methods that include: intravenous, intravascular, intracerebral, parenteral, intraperitoneal, epidural, intra-spinal, intrastemal, intra-articular, intra-synovial, intrathecal, intra-arterial, intracardiac, or intramuscular methods. Other methods such as topical, gastrointestinal, and intranasal are not taught. Thus, applicants are not entitled to all methods of administration.
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 1-13 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. The claim recites “a method for treating sepsis, in particular septic shock.” It is not clear if the method is designed for broadly treating sepsis or is for treating “septic shock.”
Claims 2 and 3 mention “the expression level.” An expression level is not mentioned in independent claim 1 so there is no proper antecedent basis. The claim should be amended to recite –an expression--.
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.
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.
Claims 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Dalemans (WO 2016001846) in view of Chao “An increase in CD3CD4CD25 Regulatory T cells after Administration of Umbilical Cord Derived Mesenchymal Stem Cells during Sepsis” PLOS ONE October 2014, Volume 9, Issue 9. All references are listed in the IDS dated 3/19/2024 and are already of record.
Dalemans teaches a method of treating sepsis in a subject in need thereof, comprising administering to said subject thawed human mesenchymal stem cells derived from umbilical cord material (Abstract, and Page 8, line 7; Page 12, line 27 of Dalemans) Dalemans further teaches that the mesenchymal stem cells can be further cryopreserved, subsequently thawed, and then placed in a pharmaceutical composition (Page 16, line 30-Page 17, line 5) as in instant Claims 1 and 14.
While Dalemans states that mesenchymal stem cells can be derived from umbilical cord material, Dalemans fails to state specifically what part of umbilical cord material is used to harvest mesenchymal stem cells. Chao teaches that umbilical cord mesenchymal stem cells can be successfully harvested from Wharton’s jelly (Page 2, Isolation of MSCs from umbilical—Chao). It would have been obvious to an artisan of ordinary skill in the art at the time of effective filing to have harvested the mesenchymal stem cells from Wharton’s jelly as taught in Chao. An artisan would have been motivated to have harvested the mesenchymal stem cells from Wharton’s jelly because those specific mesenchymal stem cells were found to modulate the immune system and attenuate sepsis (Abstract of Chao). Because such cells can treat sepsis, there would have been a high expectation for success (Abstract of Chao) as in instant Claim 14.
The combination of the Dalemans and Chao teach administering mesenchymal stem cells derived from Wharton’s jelly to treat sepsis. Dalemans teaches that such cells can be thawed which would expose the mesenchymal stem cells to the same conditions as applicants cells recited in the instant claims. Thus, it would be expected that such thawed cells would have the following characteristics when compared to fresh mesenchymal stem cells: at least 10% lower expression of the CD44 marker, at least 10% lower expression in CD90, expresses protein ACTB, secretes BMP-7, does not substantially produce ACTS and IGFBP-1, secrete at least 1.2 more VEGF, induce an increase in the VEGF concentration in patients by at least 5% compared to fresh human MSC from Wharton’s jelly as in instant Claims 1-10 and 14.
Dependent Claims taught by Dalemans
The administered MSC cells taught by Dalemans would be considered MSC clinical grade cells because they are administered into actual subjects to treat sepsis (Abstract of Dalemans) as in instant Claim 12. Page 17, lines 1-2 state that reculturing after thawing is optional and not required as in instant Claim 13.
Dependent Claims taught by Chao
Chao teaches that the MSC cells are from human umbilical cord tissue comprising from a mother having given birth at term (Page 2, Isolation of MSCs from umbilical cords) as in instant Claim 11.
Dalemans teaches administering thawed mesenchymal stem cells to a patient in need to treat sepsis. Dalemans teaches that the mesenchymal cells can be from umbilical cord material. Dalemans does not specify that such cells are derived from Whartons’ jelly. However, Chao teaches that mesenchymal stem cells derived from Wharton’s jelly are known to be able to treat sepsis. Given the teachings of the cited references and the level of skill of an artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and cell culture.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,963,984. The claims of Patent 11,963,984 represent more detailed species of the instant set of claims. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of Patent 11,963,984 recites a method for treating sepsis by administering thawed mesenchymal stem cells derived from Wharton’s jelly. Instant claim 2 corresponds to claims 2 and 3 of Patent 11,963,984. Instant claim 4 corresponds to claim 4 of Patent 11,963,984. Instant claim 5 corresponds to claim 5 of Patent 11,963,984. Instant claim 6 corresponds to claim 6 of Patent 11,963,984. Instant claim 7 corresponds to claim 7 of Patent 11,963,984. Instant claim 8 corresponds to claim 8 of Patent 11,963,984. Instant claim 9 corresponds to claim 9 of Patent 11,963,984. Instant claim 10 corresponds to claim 10 of Patent 11,963,984. Instant claim 11 corresponds to claim 11 of Patent 11,963,984. Instant claim 12 corresponds to claim 12 of Patent 11,963,984. Instant claim 13 corresponds to claim 13 of Patent 11,963,984. Instant claim 14 corresponds to claim 14 of Patent 11,963,984.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
