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 SEQ ID NO: 16 in the reply filed on November 7, 2025, is acknowledged. The elected species was searched and prior art was found on SEQ ID NO: 16 as well as on SEQ ID NOs: 2-17 and 19. Upon further consideration, the election of species requirement mailed October 1, 2025, is withdrawn.
Priority
Applicant cannot rely upon the certified copy of the foreign priority application to overcome a prior art rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
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.
Factual Findings Relevant to Both Written Description and Enablement
Nature of the Invention
The claims relate to peptides having an activity of mobilizing mesenchymal stem cells and the use of the peptides for treating diseases by mobilizing mesenchymal stem cells. The peptides are derived from an artificial peptide called 1r10 (SEQ ID NO: 1) previously reported by the inventors in PCT/JP2019/039232.
Scope of the Claims
SEQ ID NO: 1 is a 30 amino acid peptide that comprises SEQ ID NOs: 17 and 19:SEQ ID NO: 1 IMWLCQYFFQCHKCAVKKKTWKEKKDRRHP
SEQ ID: 17
SEQ ID NO: 1 IMWLCQYFFQCHKCAVKKKTWKEKKDRRHP
SEQ ID: 19
BRI of a peptide “wherein the peptide is 29 amino acids or less in length” and is “(a) a peptide consisting of a portion of the amino acid sequence of SEQ ID NO: 1, and wherein the portion comprises the amino acid sequence of SEQ ID NO: 17 or 19” is a peptide that is 1) 29 amino acids or less in length, 2) cannot contain any elements that are not recited in the claim, 3) comprises SEQ ID NO: 17 or 19, and 4) any additional amino acids N- or C-terminal to SEQ ID NO: 17 or 19 in the peptide are 100% identical to the corresponding sequence in SEQ ID NO: 1. This subgenus is limited to 106 possible peptide fragments.1
BRI of a peptide “wherein the peptide is 29 amino acids or less in length” and is “(b) a peptide consisting of all or a portion of an amino acid sequence resulting from substitution, deletion, insertion, or addition of one to five amino acids in the amino acid sequence of SEQ ID NO: 1, wherein the peptide portion comprises the amino acid sequence of SEQ ID NO: 17 or 19” is a peptide that is 1) 29 amino acids or less in length, 2) cannot contain any elements that are not recited in the claim, 3) comprises SEQ ID NO: 17 or 19, and 4) any additional amino acids N- or C-terminal to SEQ ID NO: 17 or 19 in the peptide result from substitution, deletion, insertion, or addition of one to five amino acids in the corresponding sequence in SEQ ID NO: 1. This subgenus is broad, allowing for countless modifications to the 106 possible peptide fragments of part (a) wherein outside of the region corresponding to SEQ ID NOs: 17 or 19 (i) one to five amino acids may be substituted with any of the other 19 amino acids or any unnatural amino acid, (ii) one to five amino acids may be deleted, or (iii) one to five amino acids of any type, natural or unnatural, may be added to the terminus or inserted within the sequence.
BRI of a peptide “wherein the peptide is 29 amino acids or less in length” and is “(c) a peptide consisting of all or a portion of an amino acid sequence having a sequence identity of 90% or higher with the amino acid sequence of SEQ ID NO: 1, wherein the peptide portion comprises the amino acid sequence of SEQ ID NO: 17 or 19” is a peptide that is 1) 29 amino acids or less in length, 2) cannot contain any elements that are not recited in the claim, 3) comprises SEQ ID NO: 17 or 19, and 4) any additional amino acids N- or C-terminal to SEQ ID NO: 17 or 19 in the peptide result from substitution, deletion, insertion, or addition of amino acids in the corresponding sequence in SEQ ID NO: 1 such that the identity between the peptide and SEQ ID NO: 1 is 90% or higher. This subgenus is broad, allowing for countless modifications to the 106 possible peptide fragments of part (a) wherein outside of the region corresponding to SEQ ID NOs: 17 or 19, depending on the total length of the peptide, (i) one to three amino acids may be substituted with any of the other 19 amino acids or any unnatural amino acid, (ii) one to three amino acids may be deleted, or (iii) one to three amino acids of any type, natural or unnatural, may be added to the terminus or inserted within the sequence.
BRI of effective amount in claims 1 and 11 is an amount of the peptide required to mobilize mesenchymal stem cells into peripheral blood of a subject. The methods of claims 1 and 11 are in vivo.
BRI of effective amount in claims 2 and 12 is an amount of the peptide required to mobilize mesenchymal stem cells into peripheral blood of a subject sufficient to treat a disease or pathological condition. The scope of the genus “disease or pathological condition” is broad, encompassing all diseases and conditions that can be treated by mesenchymal stem cell mobilization. In claim 4, the disease is an inflammatory disease, an autoimmune disease, a disease accompanied by tissue damage, ischemia, or necrosis, and a fibrotic disease. The scope of the subgenus “disease or pathological condition” in claim 4 is also broad, encompassing all diseases and conditions in these categories, each of which are broad, complex, and unpredictable, that can be treated by mesenchymal stem cell mobilization. In claims 5-8, the disease is inflammatory bowel disease, ulcerative colitis, atopic dermatitis, and cerebral infarction, respectively.
BRI of effective amount in claims 9 and 13 is an amount of the peptide required to mobilize mesenchymal stem cells into peripheral blood of a subject sufficient to inflammatory bowel disease, atopic dermatitis, or cerebral infarction.
Actual Reduction to Practice/Working Examples
The original specification discloses peptides that meet the structural requirements of the claims: SEQ ID NOs: 2-19. Each of SEQ ID NOs: 2-19 is 29 amino acids in length or less and consists of an amino acid sequence that is 100% to a fragment of SEQ ID NO:1 comprising SEQ ID NO: 17 or 19. The specification does not disclose any peptides with variation N- or C-terminal to the sequence corresponding to SEQ ID NO: 17 or 19.
The original specification discloses a mouse model for mesenchymal stem cell migration into peripheral blood and tests SEQ ID NOs: 2-19 in this model versus SEQ ID NO: 1 as the positive control and saline and DMSO as the negative controls (Example 1). Test substance was administered into the tail vein. After sixteen hours, peripheral blood was collected from the heart and cultured. The number of colonies detected in solid-phase culture of peripheral blood after administration of a test substance is an indicator of the activity of the test substance to mobilize mesenchymal stem cells into peripheral blood.
The results are shown in Figures 1-2 and peptides defined in Table 2:
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495
612
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Greyscale
Long horizontal bars represent the mean value and short horizontal bars represent the standard deviation. The specification states (para [0088]): “the number of colonies used as a threshold value was set to "10" colonies, and the test substance that resulted in formation of "10 or more" colonies even once out of the 4 to 6 times the assay was performed was determined to be a substance having an activity to mobilize MSC into blood”. Using this standard, the specification concludes that on the N-terminal side, 10 or more colonies were formed from the groups administered with 1r10_N03-N07, N11-12, N14, and MF5, and the number of colonies formed was less than 10 for the group administered with 1r10_N15 (Fig. 1) and that on the C-terminal side, 10 or more colonies formed from the groups administered with 1r10_C05, C10-12, and C15-C17, and the number of colonies formed was less than 10 for the group administered with Ir10_C18 (Fig. 2) (para [0089]). Based on these results, the specification concludes that the amino acid sequences of Ir10_MF5 (SEQ ID NO: 17) and Ir10_C17 (SEQ ID NO: 19) are important core sequences for maintaining the activity to mobilize MSC into blood (para [0089]).
However, the conclusion in Example 1 is not consistent with the mean and standard deviations presented in Figures 1 and 2. None of the peptides other that Ir10 have a mean that is a standard deviation above the threshold of 10. The mean for N03, N11, and C10 are above the threshold however the standard deviations are large and encompass the threshold. There does not appear to be a single peptide reduced to practice that meets the structural requirements of the claims and that demonstrate statistically significant activity in the mesenchymal stem cell mobilization model.
The specification fails to reduce to practice treatment of any disease with any peptides that meet the structural requirements of the claims. The animal models for inflammatory bowel disease, atopic dermatitis, and cerebral infarction in the Examples only include testing Ir10 (SEQ ID NO: 1), which is outside the scope of the claims.
Written Description Rejection
Claims 1-2 and 4-9 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.
MPEP § 2163 states that 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, 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.
Only those sequences meeting the structural and functional requirements of the genus are encompassed by the claim. Therefore, the claim encompasses all of the sequences meeting the structural requirements of the claims presented above that are also able to mobilize mesenchymal stem cells in a subject (claim 1) sufficient to treat a disease (claims 2 and 4-9). Although with the aid of a computer it may be possible to determine the amino acid sequences of the peptides that meet the structural requirements of the claims, it is not readily apparent from the claims or the specification which of these sequences are also able to mobilize mesenchymal stem cells in a subject (claim 1) sufficient to treat a disease (claims 2 and 4-9).
As described above the specification fails to reduce to practice any peptides for treatment of diseases encompasses by claims 2 and 4-9. With respect to claim 1, none of the peptides reduced to practice demonstrate statistically significant ability to mobilize mesenchymal stem cells. Therefore, the specification has not established written description of the claims by actual reduction to practice.
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the alleged mesenchymal stem cell mobilization activity and therefore do not describe which substitutions, deletions or additions could be made adjacent to SEQ ID NOs: 17 and 19 while preserving function. The specification does not describe any mechanism of action for the peptides. It is not disclosed how Ir10 operates, which proteins or other macromolecules it binds to, and which residues form the binding site, influence the binding site formation indirectly, contact the binding site in the folded peptide, or have a role in the overall stability and dynamics of the folded protein. Understanding the physical basis for mesenchymal stem cell mobilization activity is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus.
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the 30 amino acids of SEQ ID NO: 1 in mesenchymal stem cell mobilization are not described. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed activity.
In addition, the specification has failed to establish a nexus between the reported activity in Example 1 and an ability to treat any disease including inflammatory bowel disease, atopic dermatitis, and cerebral infarction. It is not clear from Example 1 that even the peptides reduced to practice in the specification possess significant activity to be useful in the manner that Ir10 is useful let alone peptides with variation N- and C-terminal to SEQ ID NOs: 17 and 19.
Solid state peptide synthesis and the cloning, recombinant expression and purification of proteins is well-known in the art. It is not disputed that one of ordinary skill in the art could make, albeit with route experimentation and optimization, a peptide of a given sequence provided that the sequence is known. Where the specification fails to provide description is in the structure of the peptide to make. For all of the reasons presented above, one of ordinary skill in the art would not know which of the countless peptides that meet the structural requirements of the claims would also be able to mobilize mesenchymal stem cells (claim 1) and to an extent needed to treat a disease (claims 2 and 4-9) mobilization. The specification does not make clear which peptides are in the genus and which are not because it does not describe the physical basis for the claimed activity, mesenchymal stem cell mobilization. In other words, the specification does not describe which peptides to make.
In addition, there is a high level of unpredictability and complexity associated with regenerative medicine and the use of designed peptides to induce mesenchymal stem cell mobilization. The prior art does not present clear rules to distinguish peptide that meet the structural requirements of the claims that would also be able to mobilize mesenchymal stem cells (claim 1) and to an extent needed to treat a disease (claims 2 and 4-9) mobilization from those that are not capable of this activity.
For these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Enablement Rejection
Claims 1-2 and 4-13 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 using SEQ ID NOs: 2-19 in a mouse model for mesenchymal stem cell mobilization, does not reasonably provide enablement for using SEQ ID NOs: 2-19 to treat a disease or for using any other claimed peptide for any purpose. 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.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention
The claims relate to peptides having an activity of mobilizing mesenchymal stem cells and the use of the peptides for treating diseases by mobilizing mesenchymal stem cells. The peptides are derived from an artificial peptide called 1r10 (SEQ ID NO: 1) previously reported by the inventors in PCT/JP2019/039232.
The breadth of the claims
As described in the claim interpretation section above, the claims are broad with respect to the structure of the peptides and their function.
Working Examples
As described above, the specification fails to reduce to practice any peptides for treatment of diseases encompasses by claims 2 and 4-9. With respect to claim 1, none of the peptides reduced to practice demonstrate statistically significant ability to mobilize mesenchymal stem cells. With respect to claim 10, SEQ ID NOs: 2-19 are not representative of the full scope of the peptide genus. There is no established use for peptides with variation N- and C-terminal to SEQ ID NOs: 17 and 19.
The Level of Guidance in the Specification
The level of guidance in the specification is insufficient to determine which of the countless species encompassed by the claim can be used in the claimed method.
The data presented in the specification raise more questions about the physical properties of the genus than they answer. The data do not suggest the physical basis for the alleged mesenchymal stem cell mobilization activity and therefore do not describe which substitutions, deletions or additions could be made adjacent to SEQ ID NOs: 17 and 19 while preserving function. The specification does not describe any mechanism of action for the peptides. It is not disclosed how Ir10 operates, which proteins or other macromolecules it binds to, and which residues form the binding site, influence the binding site formation indirectly, contact the binding site in the folded peptide, or have a role in the overall stability and dynamics of the folded protein. Understanding the physical basis for mesenchymal stem cell mobilization activity is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus.
The specification does not describe a general correlation between structure and function for the claimed genus. The role of the 30 amino acids of SEQ ID NO: 1 in mesenchymal stem cell mobilization are not described. As a result, it is impossible to predict, based on the specification, how changing any position will affect the claimed activity.
In addition, the specification has failed to establish a nexus between the reported activity in Example 1 and an ability to treat any disease including inflammatory bowel disease, atopic dermatitis, and cerebral infarction. It is not clear from Example 1 that even the peptides reduced to practice in the specification possess significant activity to be useful in the manner that Ir10 is useful let alone peptides with variation N- and C-terminal to SEQ ID NOs: 17 and 19.
The State of the Prior Art
The closest prior art of Tamai et al. (WO 2020/071520; English language equivalent US 2022/0009976 A1) teaches a peptide with an activity of mobilizing mesenchymal stem cells into peripheral blood. The peptide is SEQ ID NO: 1.2 Tamai et al. teach that the peptide includes peptides that are 10 to 100 amino acids in length that:
comprise or consist of the amino acid sequence of SEQ ID NO: 1;
consist of a portion of the amino acid sequence of SEQ ID NO: 1;
comprise or consist of an amino acid sequence resulting from substitution, deletion, insertion, or addition of one to five amino acids in the amino acid sequence of SEQ ID NO: 1; or
comprise or consist of an amino acid sequence having about 90% or more sequence identity with the amino acid sequence of SEQ ID NO: 1 (para. [0102]-[0104]).
The genus of peptides include instantly claimed peptides. However, Tamai et al. also fail to provide a structure-function correlation for SEQ ID NO: 1 that could be used to enable the instantly claimed genus.
The Predictability or Unpredictability of the Art
There is a high level of unpredictability and complexity associated with regenerative medicine and the use of designed peptides to induce mesenchymal stem cell mobilization. The prior art does not present clear rules to distinguish peptide that meet the structural requirements of the claims that would also be able to mobilize mesenchymal stem cells (claim 1) and to an extent needed to treat a disease (claims 2 and 4-9) mobilization from those that are not capable of this activity.
The Quantity of Experimentation Necessary
Considering the factors above, the skilled artisan would be burdened with undue experimentation in determining if one of the claimed peptides would be effective at mobilizing mesenchymal stem cells into peripheral blood in a subject at all let alone for the purpose of treating a disease. The skilled artisan would be burdened with testing a broad range of peptides in an animal model for mesenchymal stem cell migration. The active peptides would then have to be subjected to animal models relevant to the full scope of the claimed diseases. The experimentation required represents years of inventive effort. When the above factors are weighed, it is the examiner's position that one skilled in the art could not practice the invention without undue experimentation.
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention. Only a method for using SEQ ID NOs: 2-19 in a mouse model for mesenchymal stem cell mobilization is enabled.
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.
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 10 and 14 are rejected under 35 U.S.C. 103 as being obvious over Tamai et al. (WO 2020/071520; English language equivalent US 2022/0009976 A1)3.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
Determining the scope and contents of the prior art.
Tamai et al. teach a peptide with an activity of mobilizing mesenchymal stem cells into peripheral blood. The peptide is SEQ ID NO: 1.4 Tamai et al. teach that the peptide includes peptides that are 10 to 100 amino acids in length that:
comprise or consist of the amino acid sequence of SEQ ID NO: 1;
consist of a portion of the amino acid sequence of SEQ ID NO: 1;
comprise or consist of an amino acid sequence resulting from substitution, deletion, insertion, or addition of one to five amino acids in the amino acid sequence of SEQ ID NO: 1; or
comprise or consist of an amino acid sequence having about 90% or more sequence identity with the amino acid sequence of SEQ ID NO: 1 (para. [0102]-[0104]).
The genus of peptides and the subgenus consisting of a portion of SEQ ID NO: 1 include instantly claimed SEQ ID NOs: 2-17 and 19.
Ascertaining the differences between the prior art and the claims at issue.
Tamai et al. does not reduce to practice peptides consisting of SEQ ID NOs: 2-17 and 19.
Resolving the level of ordinary skill in the pertinent art.
It is within the ordinary skill of the art to identify fragments of a peptide when provided with the amino acid sequence of a peptide.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The instant application has not demonstrated that the claimed fragments consisting of instant SEQ ID NOs: 2-17 and 19 have unexpected properties. The specification states (para [0088]): “the number of colonies used as a threshold value was set to "10" colonies, and the test substance that resulted in formation of "10 or more" colonies even once out of the 4 to 6 times the assay was performed was determined to be a substance having an activity to mobilize MSC into blood”. Using this standard, the specification concludes that on the N-terminal side, 10 or more colonies were formed from the groups administered with 1r10_N03-N07, N11-12, N14, and MF5 (SEQ ID NOs: 2-9 and 19), and the number of colonies formed was less than 10 for the group administered with 1r10_N15 (SEQ ID NO: 10) (Fig. 1) and that on the C-terminal side, 10 or more colonies formed from the groups administered with 1r10_C05, C10-12, and C15-C17 (SEQ ID NOs: 11-17), and the number of colonies formed was less than 10 for the group administered with Ir10_C18 (SEQ ID NO: 18) (Fig. 2) (para [0089]). Based on these results, the specification concludes that the claimed sequences have the activity predicted in the prior art, which is an expected, not unexpected result.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the peptides in the subgenus consisting of a portion of the amino acid sequence of SEQ ID NO: 1 disclosed by Tamai et al. In doing so, one of ordinary skill in the art would make instantly claimed peptides consisting of SEQ ID NOs: 2-17 and 19. The rationale for obviousness is "obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success (MPEP § 2143.01(E)). The relevant findings for this rationale are as follows.
(1) At the relevant time, there had been a recognized problem or need in the art, which may include a design need or market pressure to solve a problem. In the instant case, Tamai et al. teaches that there is a need to develop new regenerative medicine technology that can overcome the problems of cell transplantation therapy (para [0002]):
Mesenchymal stem cells contained in bone marrow fluid and the like have the ability to differentiate into various tissues (pluripotency) such as bone, cartilage, fat, muscle, nerve, and epithelium. In recent years, attempts have been widely made to perform regenerative medicine (cell transplantation therapy) using bone marrow-derived mesenchymal stem cells proliferated by culture. However, collection of bone marrow blood containing mesenchymal stem cells is done with an invasive technique which inserts a thick needle into the iliac bone repeatedly, thereby placing a large burden on the donor. In addition, mesenchymal stem cells gradually lose their proliferative ability and pluripotency when subcultured continuously in vitro. Furthermore, culturing mesenchymal stem cells based on high quality control that guarantees the safety of in vivo transplantation requires special culture equipment such as CPC (cell processing center), so the current situation is that it can be carried out only at a limited number of universities and companies.
Therefore, there had been a recognized problem or need in the art, which may include a design need or market pressure to solve a problem.
(2) There had been a finite number of identified, predictable potential solutions to the recognized need or problem. Tamai et al. teach a peptide with an activity of mobilizing mesenchymal stem cells into peripheral blood. The peptide is SEQ ID NO: 1.5 Tamai et al. teach that the peptide includes peptides that are 10 to 100 amino acids in length that:
comprise or consist of the amino acid sequence of SEQ ID NO: 1;
consist of a portion of the amino acid sequence of SEQ ID NO: 1;
comprise or consist of an amino acid sequence resulting from substitution, deletion, insertion, or addition of one to five amino acids in the amino acid sequence of SEQ ID NO: 1; or
comprise or consist of an amino acid sequence having about 90% or more sequence identity with the amino acid sequence of SEQ ID NO: 1 (para. [0102]-[0104]).
There are 231 unique amino acid sequences in the subgenus taught by Tamai et al. that consist of a portion of SEQ ID NO: 1 that are 10 amino acids in length or more. The number of amino acid sequences that consist of a portion of SEQ ID NO: 1 that are 10 amino acids in length or more (231) is comparable to the number the courts held as a finite in Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) (the court rejected the notion that unpredictability could be equated with nonobviousness here, because there were only a finite number (53) of pharmaceutically acceptable salts to be tested for improved properties). Therefore, Tamai et al. teach a finite number of identified, predictable potential solutions to the recognized need or problem.
(3) One of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success. One of ordinary skill in the art would expect that the 231 unique amino acid sequences in the subgenus taught by Tamai et al. that consist of a portion of SEQ ID NO: 1 that are 10 amino acids in length or more could be tested in the disclosed model for mesenchymal stem cell mobility presented in Example 1 of Tamai et al. because the reference teaches that this is the intended function and activity of the genus. In addition, Tamai et al. demonstrate in Example 1 how to conduct the assay with the full length peptide SEQ ID NO: 1. Therefore, one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
(4) Whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness. The instant application has not demonstrated that the claimed fragments consisting of instant SEQ ID NOs: 2-17 and 19 have unexpected properties. The specification states (para [0088]): “the number of colonies used as a threshold value was set to "10" colonies, and the test substance that resulted in formation of "10 or more" colonies even once out of the 4 to 6 times the assay was performed was determined to be a substance having an activity to mobilize MSC into blood”. Using this standard, the specification concludes that on the N-terminal side, 10 or more colonies were formed from the groups administered with 1r10_N03-N07, N11-12, N14, and MF5 (SEQ ID NOs: 2-9 and 19), and the number of colonies formed was less than 10 for the group administered with 1r10_N15 (SEQ ID NO: 10) (Fig. 1) and that on the C-terminal side, 10 or more colonies formed from the groups administered with 1r10_C05, C10-12, and C15-C17 (SEQ ID NOs: 11-17), and the number of colonies formed was less than 10 for the group administered with Ir10_C18 (SEQ ID NO: 18) (Fig. 2) (para [0089]). Based on these results, the specification concludes that the claimed sequences have the activity predicted in the prior art, which is an expected, not unexpected result.
The rationale to support a conclusion that the claim would have been obvious is that "a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103."KSR, 550 U.S. at 421, 82 USPQ2d at 1397.
Therefore, claims 10 and 14 are obvious over the cited art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654
1 SEQ ID NO: 17 is amino acids 18-30 of SEQ ID NO: 1. Therefore, fragments consisting of residues 2-30, 3-30, 4-30… 18-30 of SEQ ID NO: 1 meet the requirement wherein the peptide is 29 amino acids or less in length and is a peptide consisting of a portion of the amino acid sequence of SEQ ID NO: 1, and wherein the portion comprises the amino acid sequence of SEQ ID NO: 17.
SEQ ID NO: 19 is amino acids 6-16 of SEQ ID NO: 1. Therefore, fragments consisting of residues 6-16, 6-17, 6-18… 6-30, 5-16, 5-17, 5-18… 5-30, 4-16, 4-17, 4-18… 4-30, 3-16, 3-17, 3-18… 3-30, 2-16, 2-17, 2-18… 2-30, and 1-16, 1-17, 1-18… 1-29 of SEQ ID NO: 1 meet the requirement wherein the peptide is 29 amino acids or less in length and is a peptide consisting of a portion of the amino acid sequence of SEQ ID NO: 1, and wherein the portion comprises the amino acid sequence of SEQ ID NO: 19.
2 SEQ ID NO: 1 in Tamai et al. is identical to instant SEQ ID NO: 1.
3 WO 2020/071520 A1 was published 9 April 2020, filed 10 April 2019, and claims priority to JP 2018-190090 filed 5 October 2018. The instant application was filed 2 April 2021. Priority to JP 2020-067570, filed 3 April 2020, is not granted because no translation has been filed. There is one additional inventor listed on WO 2020/071520 A1, Koichi Yokota. Therefore, WO 2020/071520 A1 was published (9 April 2020) and filed (5 October 2018) prior to the effective filing date of the instant application (2 April 2021) and qualifies as prior art under 35 U.S.C. 102(a)(1) and 102(a)(2) with a common inventor.
4 SEQ ID NO: 1 in Tamai et al. is identical to instant SEQ ID NO: 1.
5 SEQ ID NO: 1 in Tamai et al. is identical to instant SEQ ID NO: 1.