DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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 for the cited rejections 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.
3. Response to Election/Restriction filed on 6/10/2026 is acknowledged.
4. Claim filed on 6/10/2026 is acknowledged.
5. Claims 1-13 are pending in this application.
6. Claims 1-13 are under examination.
Election/Restrictions
7. Applicant’s election without traverse of small molecular inhibitors as species of CD226 inhibitor; and mouse osteosarcoma cell line K7M2 as species of tumor in the reply filed on 6/10/2026 is acknowledged. Since the elected species of CD226 inhibitor is a subgenus, not a species; the Examiner telephoned Applicant’s representative, Scott A. Woodbury, for further species election. Applicant’s representative elected on the phone that angiotensin III having the property of reducing platelet activation and inhibiting tumor metastasis as the elected species of CD226 inhibitor on 6/24/2026. The requirement is made FINAL in this office action.
The instant claims 1-13 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules. A search was conducted on the elected species; and angiotensin III having the property of reducing platelet activation and inhibiting tumor metastasis as the elected species of CD226 inhibitor appears to be free of prior art. However, prior art was found for mouse osteosarcoma cell line K7M2 as the elected species of tumor. A search was extended to the genus in claim 1; and prior art was found. Claims 1-13 are examined on the merits in this office action.
Specification
8. Please note: The specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification (see MPEP § 608.01).
Objections
9. The drawings are objected to for the following minor informality:
Figure 2: Legend for X-axis and Y-axis is missing.
Figure 8: Applicant is required to remove the Chinese characters in figure 8.
Figures 9A and 9B: Each of these figures requires its individual description.
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.
10. Claim 1 is objected to for the following minor informality: Claim 1 contains the acronym “CD226”. An acronym in the first instance of claims should be expanded upon/spelled out with the acronym indicated in parentheses, i.e., cluster of differentiation 226 (CD226). The abbreviation can be used thereafter.
Furthermore, Applicant is suggested to amend claim 1 as “A method of inhibiting tumor metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of cluster of differentiation 226 (CD226) inhibitor, and wherein the CD226 inhibitor is configured to target CD226 molecules”.
11. Claim 3 is objected to for the following minor informality: Applicant is suggested to amend claim 3 as “…wherein interfering with the CD226 molecules on the platelets reduces platelet activation and inhibits tumor metastasis”.
12. Claims 7 and 9-12 are objected to for the following minor informality: Applicant is suggested to amend these claims as “…wherein the tumor is derived from mouse osteosarcoma cell line K7M2”.
Rejections
Claim Rejections - 35 U.S.C. § 112 paragraph (b)
13. 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.
14. Claims 4, 5, 8, 11 and 12 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 pre-AIA the applicant regards as the invention.
15. Claim 4 recites “The method according to claim 2, wherein the CD226 molecules serve as a site which regulates interaction of the platelets and tumor cells, and the CD226 inhibitor for inhibiting tumor metastasis are prepared accordingly”. In the instant case, the method recited in instant claim 4 is a method of inhibiting tumor metastasis with a CD226 inhibitor that is configured to target CD226 molecules. The CD226 inhibitor used in the method has already been prepared. Therefore, it is unclear what is encompassed within the recited “and the CD226 inhibitor for inhibiting tumor metastasis are prepared accordingly”. Thus, the metes and bounds of instant claim 4 is vague and indefinite. Because claim 11 depends from indefinite claim 4, and it does not clarify the point of confusion, it must also be rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
Furthermore, for the purpose of this examination, the recited “and the CD226 inhibitor for inhibiting tumor metastasis are prepared accordingly” would not be searched and examined in the current office action. And claim 4 is interpretated as “The method according to claim 2, wherein the CD226 molecules serve as a site which regulates interaction of the platelets and tumor cells”. Such interpretation applies to all the rejections set forth below.
16. Claim 5 recites the limitation “CD226 inhibitor is a small-molecule inhibitor”. With regards to the term “small-molecule inhibitor”, the instant specification fails to define it. And the small-molecule inhibitors recited in instant claim 6 include both chemical compounds and peptides. Therefore, it is unclear what is encompassed within the recited “small-molecule inhibitor”. Thus, the metes and bounds of instant claim 5 is vague and indefinite. Because claim 12 depends from indefinite claim 5, and it does not clarify the point of confusion, it must also be rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
17. Claim 8 recites “The method according to claim 2, wherein the CD226 molecules serve as a site which regulates interaction of the platelets and tumor cells, and a tumor detection kit is prepared accordingly”. In the instant case, the method recited in instant claim 4 is a method of inhibiting tumor metastasis with a CD226 inhibitor that is configured to target CD226 molecules. The tumor in the subject has already been detected. It is unclear how and/or why “and a tumor detection kit is prepared accordingly” is related to the instant claimed method, and it is also unclear what kind of tumor detection kit is prepared. Taken all these together, the metes and bounds of instant claim 8 is vague and indefinite.
Furthermore, for the purpose of this examination, the recited “and a tumor detection kit is prepared accordingly” would not be searched and examined in the current office action. And claim 8 is interpretated as “The method according to claim 2, wherein the CD226 molecules serve as a site which regulates interaction of the platelets and tumor cells”. Such interpretation applies to all the rejections set forth below.
Claim Rejections - 35 U.S.C. § 112 paragraph (a)
Written Description
18. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
19. Claims 1-5 and 7-12 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient” (MPEP § 2163).
A claimed genus may be satisfied through sufficient description of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure (MPEP § 2163(3)a(II)). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
In the instant case, claims 1-5 and 7-12 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules.
The genus of instant claimed CD226 inhibitor is extremely broad, including any agent that is configured to target CD226 molecules; and instant claim 5 limits the CD226 inhibitor to small molecular inhibitor, which appears to broadly includes peptide and chemical compound.
The issue at question is whether a person of ordinary skilled in the art would be able to determine what structural feature is required for an agent to have the functional characteristics of being an CD226 inhibitor that is configured to target CD226 molecules or not.
(a) actual reduction to practice and (b) disclosure of drawings or structural chemical formulas:
In the instant case, the instant specification discloses the 10 compounds and/or peptides recited in instant claim 6 as candidate CD226 inhibitor via computer molecular docking. The instant specification further discloses the 10 compounds and/or peptides recited in instant claim 6 inhibit the adhesion between tumor cells and platelets. However, there is no data indicating such inhibiting effect is due to the 10 compounds and/or peptides recited in instant claim 6 are CD226 inhibitor; and there is no data showing any effect of the 10 compounds and/or peptides recited in instant claim 6 on CD226 molecule. Furthermore, there is no common core structure shared by the 10 compounds and/or peptides recited in instant claim 6.
Taken all these together, other than the limited examples, the instant specification fails to describe what structural feature is required for an agent to have the functional characteristics of being an CD226 inhibitor that is configured to target CD226 molecules.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure:
As discussed above, in the instant case, based on the disclosure of instant specification, other than the limited examples, a person of ordinary skilled in the art would not be able to determine what structural feature is required for an agent to have the functional characteristics of being an CD226 inhibitor that is configured to target CD226 molecules.
With regards to the instant claimed CD226 inhibitor that is configured to target CD226 molecules, O'Leary et al (US 2021/0032700 A1) teach antibody that has specific binding affinity for CD226 as CD226 inhibitor that is configured to target CD226 molecules, for example, page 4, paragraph [0052]; and page 7, paragraph [0074]. Other than the antibody disclosed in O'Leary et al, a CD226 inhibitor that is configured to target CD226 molecules is unknown in the art.
Therefore, based on the state of art, a person of ordinary skilled in the art would not be able to determine what structural feature is required for an agent to have the functional characteristics of being an CD226 inhibitor that is configured to target CD226 molecules.
(d) representative number of samples:
In the instant case, the genus of instant claimed CD226 inhibitor is extremely broad, including any agent that is configured to target CD226 molecules; and instant claim 5 limits the CD226 inhibitor to small molecular inhibitor, which appears to broadly include peptide and chemical compound.
And, as discussed in (a) and (b) above, the instant specification discloses the 10 compounds and/or peptides recited in instant claim 6 as candidate CD226 inhibitor via computer molecular docking. The instant specification further discloses the 10 compounds and/or peptides recited in instant claim 6 inhibit the adhesion between tumor cells and platelets. However, there is no data indicating such inhibiting effect is due to the 10 compounds and/or peptides recited in instant claim 6 are CD226 inhibitor; and there is no data showing any effect of the 10 compounds and/or peptides recited in instant claim 6 on CD226 molecule. Furthermore, there is no common core structure shared by the 10 compounds and/or peptides recited in instant claim 6.
Considering the broadness of the genus of instant claimed CD226 inhibitor, the instant specification fails to provide sufficient examples to describe the entire genus of instant claimed CD226 inhibitor that is configured to target CD226 molecules.
Taken all these together, considering the state of the art and the disclosure in instant specification, it is deemed that the instant specification fails to provide adequate written description for the claimed genus of CD226 inhibitor that is configured to target CD226 molecules; and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 U.S.C. § 112 paragraph (a)
Scope of Enablement
20. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
21. Claims 1-13 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 a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of certain CD226 inhibitor that is configured to target CD226 molecules, does not reasonably provide enablement for a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of angiotensin III.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. 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.
(1) The nature of the invention and (5) The breadth of the claims:
The instant claims 1-13 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules.
The instant claims 1-4 and 7-11 broadly include all types of CD226 inhibitor that is configured to target CD226 molecules; claim 5 limits the CD226 inhibitor to small molecular inhibitor; and claim 6 limits the CD226 inhibitor to angiotensin III, neohesperidin, [Leu5]-enkephalin, epimedin B, methylhesperidin, salvianolic acid B, bradykinin (2-9), echinacoside, astragaloside III and poliumoside.
Please note: The rejection to instant claimed CD226 inhibitor that is configured to target CD226 molecules 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 has been set forth in Section 19 above.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
With regarding to inhibiting tumor metastasis with ALL type of CD226 inhibitor that is configured to target CD226 molecules recited in instant claims, the art is unpredictable.
Kilmister et al (Biomedicines, 2022, 10, pages 1-30) teach angiotensin III (a CD226 inhibitor recited in instant claim 6) interacts with AT1R and AT2R; and promotes pathological processes including cellular proliferation, migration, invasion, metastasis and inhibition of apoptosis, for example, pages 9-10, the 1st paragraph in “Section 4.2. The Paracrine Renin-Angiotensin System”; and page 11, Figure 4.
(3) The relative skill of those in the art:
The relative skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
With regarding to inhibiting tumor metastasis with ALL type of CD226 inhibitor that is configured to target CD226 molecules recited in instant claims, the instant specification discloses interfering with CD226 molecules on the platelets is capable of reducing platelet activation and inhibiting tumor metastasis. The instant specification further discloses the 10 compounds and/or peptides recited in instant claim 6 as candidate CD226 inhibitor via computer molecular docking; and they inhibit the adhesion between tumor cells and platelets. However, there is no data indicating such inhibiting effect is due to the 10 compounds and/or peptides recited in instant claim 6 are CD226 inhibitor; and there is no data showing any effect of the 10 compounds and/or peptides recited in instant claim 6 on CD226 molecule. Furthermore, there is no data and/evidence showing inhibiting tumor metastasis in a subject in need thereof with any CD226 inhibitor that is configured to target CD226 molecules.
(8) The quantity of experimentation necessary:
Considering the state of prior arts and the disclosure in instant specification, one of ordinary skill in the art would be burdened with undue experimentation to inhibit tumor metastasis with ALL type of CD226 inhibitor that is configured to target CD226 molecules.
Claim Rejections - 35 U.S.C. § 102(a)(1)
22. 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.
23. Claims 1-5 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by O'Leary et al (US 2021/0032700 A1), and as evidenced by Kojima et al (THE JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278, pages 36748–36753).
The instant claims 1-5 and 8 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules.
O'Leary et al, throughout the patent, teach a method of inhibiting tumor metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a CD226 inhibitor, wherein the CD226 inhibitor is an antibody or fragment thereof that has specific binding affinity for CD226 and is configured to target CD226 molecules, or is a nucleic acid capable of inhibiting or reducing the expression of CD226, such as shRNA; and wherein the CD226 inhibitor inhibits platelet cloaked cancer cell formation, for example, pages 1-2, paragraphs [0007], [0012]-[0019] and [0023]; page 3, paragraph [0036]; and page 7, paragraphs [0074]-[0076]. It meets the limitations of instant claim 1; and the limitation of CD226 inhibitor recited in instant claim 5. And as evidenced by Kojima et al, CD226 molecules are located on platelets (see for example, Abstract). Therefore, the method in O'Leary et al meets the limitations of instant claim 2.
With regards to the limitations recited in instant claims 3, 4 and 8, in the instant case, since the CD226 molecules located on platelets in the method in O'Leary et al meet all the limitations of the CD226 molecules recited in instant claim 2, and the antibody or fragment thereof that has specific binding affinity for CD226 as the CD226 inhibitor in the method in O'Leary et al meets all the limitations of the CD226 inhibitor recited in instant claim 1, both the CD226 molecules located on platelets and the antibody or fragment thereof that has specific binding affinity for CD226 as the CD226 inhibitor in the method in O'Leary et al would necessarily have the same properties and/or functionalities of the CD226 molecules and the CD226 inhibitor recited in instant claims. Therefore, the CD226 molecules located on platelets in the method in O'Leary et al serve as a site which regulates interaction of the platelets and tumor cells; and the antibody or fragment thereof that has specific binding affinity for CD226 as the CD226 inhibitor in the method in O'Leary et al is capable of reducing platelet activation and inhibiting tumor metastasis. It meets the limitations of instant claims 3, 4 and 8. Furthermore, the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Since the reference teaches all the limitations of instant claims 1-5 and 8; the reference anticipates instant claims 1-5 and 8.
24. Claims 1-6 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jia et al (CN 111297943 A, machine translation used and enclosed pages 1-66), and as evidenced by Kojima et al (THE JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278, pages 36748–36753).
The instant claims 1-6 and 8 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules.
Jia et al, throughout the patent, teach a method of inhibiting tumor metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of salvianolic acid B, for example, page 7, paragraph [0009]; page 13, paragraph [0021]; and pages 30-31, paragraph [0057]. Salvianolic acid B in the method in Jia et al is a small molecular CD266 inhibitor recited in instant claim 6. Therefore, the method in Jia et al meets the limitations of instant claim 1; and the limitations of CD266 inhibitor recited in instant claims 5 and 6. And as evidenced by Kojima et al, CD226 molecules are located on platelets (see for example, Abstract). Therefore, the method in Jia et al meets the limitations of instant claim 2.
With regards to the limitations recited in instant claims 3, 4 and 8, in the instant case, since the CD226 molecules located on platelets meet all the limitations of the CD226 molecules recited in instant claim 2, and salvianolic acid B in the method of Jia et al meets all the limitations of the CD226 inhibitor recited in instant claim 1, the CD226 molecules located on platelets and salvianolic acid B as a CD226 inhibitor in the method in Jia et al would necessarily have the same properties and/or functionalities of the CD226 molecules and the CD226 inhibitor recited in instant claims. Therefore, the CD226 molecules located on platelets serve as a site which regulates interaction of the platelets and tumor cells; and salvianolic acid B as a CD226 inhibitor in the method in Jia et al is capable of reducing platelet activation and inhibiting tumor metastasis. It meets the limitations of instant claims 3, 4 and 8. Furthermore, the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Since the reference teaches all the limitations of instant claims 1-6 and 8; the reference anticipates instant claims 1-6 and 8.
25. Claims 1-6 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zeng et al (ONCOLOGY LETTERS, 2018, 15, pages 2679-2685), and as evidenced by Kojima et al (THE JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278, pages 36748–36753).
The instant claims 1-6 and 8 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules.
Zeng et al, throughout the literature, teach osteosarcoma as a primary malignant tumor with ~20% of patients exhibiting pulmonary metastasis prior to diagnosis; and anticancer effect of salvianolic acid B on osteosarcoma, for example, Abstract; page 2679, the 1st paragraph in Section “Introduction”; page 2680, Figure 1; pages 2682-2683, the 1st paragraph in Section “Discussion”; and page 2684, the last paragraph in Section “Discussion”. Therefore, in view of the teachings of Zeng et al as a whole, one of ordinary skilled in the art would at once envision a method of treating osteosarcoma in a patient in need thereof, including the ~20% of patients exhibiting pulmonary metastasis, wherein the method comprises administering to the patient a therapeutically effective amount of salvianolic acid B. Salvianolic acid B in the method above is a small molecular CD266 inhibitor recited in instant claim 6.
In the instant case, since the method above comprising administering the same compound to the same subject as the method recited in instant claim 1, the method above would necessarily result in the same effect, i.e., inhibiting tumor metastasis. Therefore, the method above meets the limitations of instant claim 1; and the limitations of CD266 inhibitor recited in instant claims 5 and 6. And as evidenced by Kojima et al, CD226 molecules are located on platelets (see for example, Abstract). Therefore, the method above meets the limitations of instant claim 2.
With regards to the limitations recited in instant claims 3, 4 and 8, in the instant case, since the CD226 molecules located on platelets meets all the limitations of the CD226 molecules recited in instant claim 2, and salvianolic acid B in the method above meets all the limitations of the CD226 inhibitor recited in instant claim 1, the CD226 molecules located on platelets and salvianolic acid B as a CD226 inhibitor in the method above would necessarily have the same properties and/or functionalities of the CD226 molecules and the CD226 inhibitor recited in instant claims. Therefore, the CD226 molecules located on platelets serve as a site which regulates interaction of the platelets and tumor cells; and salvianolic acid B as a CD226 inhibitor in the method above is capable of reducing platelet activation and inhibiting tumor metastasis. It meets the limitations of instant claims 3, 4 and 8. Furthermore, the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
Since the reference teaches all the limitations of instant claims 1-6 and 8; the reference anticipates instant claims 1-6 and 8.
Claim Rejections - 35 U.S.C. § 103
26. 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 of this title, 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.
27. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
28. Claims 1-5 and 7-12 are rejected under 35 U.S.C. 103 as being unpatentable over O'Leary et al (US 2021/0032700 A1), and as evidenced by Kojima et al (THE JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278, pages 36748–36753), and in view of Ren et al (Oncotarget, 2015, 6, pages 29469-29481).
The instant claims 1-5 and 7-12 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules.
O'Leary et al, throughout the patent, teach a method of inhibiting tumor metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a CD226 inhibitor, wherein the CD226 inhibitor is an antibody or fragment thereof that has specific binding affinity for CD226 and is configured to target CD226 molecules, or is a nucleic acid capable of inhibiting or reducing the expression of CD226, such as shRNA; and wherein the CD226 inhibitor inhibits platelet cloaked cancer cell formation, for example, pages 1-2, paragraphs [0007], [0012]-[0019] and [0023]; page 3, paragraph [0036]; and page 7, paragraphs [0074]-[0076]. It meets the limitations of instant claim 1; and the limitation of CD226 inhibitor recited in instant claim 5. And as evidenced by Kojima et al, CD226 molecules are located on platelets (see for example, Abstract). Therefore, the method in O'Leary et al meets the limitations of instant claim 2.
With regards to the limitations recited in instant claims 3, 4 and 8, in the instant case, since the CD226 molecules located on platelets in the method in O'Leary et al meet all the limitations of the CD226 molecules recited in instant claim 2, and the antibody or fragment thereof that has specific binding affinity for CD226 as the CD226 inhibitor in the method in O'Leary et al meets all the limitations of the CD226 inhibitor recited in instant claim 1, both the CD226 molecules located on platelets and the antibody or fragment thereof that has specific binding affinity for CD226 as the CD226 inhibitor in the method in O'Leary et al would necessarily have the same properties and/or functionalities of the CD226 molecules and the CD226 inhibitor recited in instant claims. Therefore, the CD226 molecules located on platelets in the method in O'Leary et al serve as a site which regulates interaction of the platelets and tumor cells; and the antibody or fragment thereof that has specific binding affinity for CD226 as the CD226 inhibitor in the method in O'Leary et al is capable of reducing platelet activation and inhibiting tumor metastasis. It meets the limitations of instant claims 3, 4 and 8. Furthermore, the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
The difference between the reference and instant claims 1-5 and 7-12 is that the reference does not explicitly teach mouse osteosarcoma cell line K7M2 as the elected species of tumor; and the limitations of instant claims 7 and 9-12.
However, O'Leary et al teach platelet cloaking of cancer cells is a universal phenomenon occurring across all tumour types, for example, page 6, paragraph [0070].
Furthermore, Ren et al teach osteosarcoma (OS) cell line K7M2 is 80% generation of spontaneous metastasis and 100% generation of experimental metastasis, for example, page 29471, Table 1.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of O'Leary et al and Ren et al and develop a method of inhibiting tumor metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a CD226 inhibitor; wherein the CD226 inhibitor is an antibody or fragment thereof that has specific binding affinity for CD226 and is configured to target CD226 molecules, wherein the CD226 inhibitor inhibits platelet cloaked cancer cell formation, and wherein the tumor can be one derived from mouse osteosarcoma cell line K7M2. It reads on mouse osteosarcoma cell line K7M2 as the elected species of tumor.
One of ordinary skilled in the art would have been motivated to combine the teachings of O'Leary et al and Ren et al and develop a method of inhibiting tumor metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a CD226 inhibitor; wherein the CD226 inhibitor is an antibody or fragment thereof that has specific binding affinity for CD226 and is configured to target CD226 molecules, wherein the CD226 inhibitor inhibits platelet cloaked cancer cell formation, and wherein the tumor can be one derived from mouse osteosarcoma cell line K7M2, because O'Leary et al teach platelet cloaking of cancer cells is a universal phenomenon occurring across all tumour types. And Ren et al teach osteosarcoma (OS) cell line K7M2 is 80% generation of spontaneous metastasis and 100% generation of experimental metastasis.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of O'Leary et al and Ren et al and develop a method of inhibiting tumor metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a CD226 inhibitor; wherein the CD226 inhibitor is an antibody or fragment thereof that has specific binding affinity for CD226 and is configured to target CD226 molecules, wherein the CD226 inhibitor inhibits platelet cloaked cancer cell formation, and wherein the tumor can be one derived from mouse osteosarcoma cell line K7M2.
29. Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng et al (ONCOLOGY LETTERS, 2018, 15, pages 2679-2685), and as evidenced by Kojima et al (THE JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278, pages 36748–36753), and in view of Ren et al (Oncotarget, 2015, 6, pages 29469-29481).
The instant claims 1-13 are drawn to a method of inhibiting tumor metastasis in a subject in need thereof, the method comprising administering to a subject a therapeutically effective amount of CD226 inhibitor; wherein the CD226 inhibitor is configured to target CD226 molecules.
Zeng et al, throughout the literature, teach osteosarcoma as a primary malignant tumor with ~20% of patients exhibiting pulmonary metastasis prior to diagnosis; and anticancer effect of salvianolic acid B on osteosarcoma, for example, Abstract; page 2679, the 1st paragraph in Section “Introduction”; page 2680, Figure 1; pages 2682-2683, the 1st paragraph in Section “Discussion”; and page 2684, the last paragraph in Section “Discussion”. Therefore, in view of the teachings of Zeng et al as a whole, one of ordinary skilled in the art would at once envision a method of treating osteosarcoma in a patient in need thereof, including the ~20% of patients exhibiting pulmonary metastasis, wherein the method comprises administering to the patient a therapeutically effective amount of salvianolic acid B. Salvianolic acid B in the method above is a small molecular CD266 inhibitor recited in instant claim 6.
In the instant case, since the method above comprising administering the same compound to the same subject as the method recited in instant claim 1, the method above would necessarily result in the same effect, i.e., inhibiting tumor metastasis. Therefore, the method above meets the limitations of instant claim 1; and the limitations of CD266 inhibitor recited in instant claims 5 and 6. And as evidenced by Kojima et al, CD226 molecules are located on platelets (see for example, Abstract). Therefore, the method above meets the limitations of instant claim 2.
With regards to the limitations recited in instant claims 3, 4 and 8, in the instant case, since the CD226 molecules located on platelets meets all the limitations of the CD226 molecules recited in instant claim 2, and salvianolic acid B in the method above meets all the limitations of the CD226 inhibitor recited in instant claim 1, the CD226 molecules located on platelets and salvianolic acid B as a CD226 inhibitor in the method above would necessarily have the same properties and/or functionalities of the CD226 molecules and the CD226 inhibitor recited in instant claims. Therefore, the CD226 molecules located on platelets serve as a site which regulates interaction of the platelets and tumor cells; and salvianolic acid B as a CD226 inhibitor in the method above is capable of reducing platelet activation and inhibiting tumor metastasis. It meets the limitations of instant claims 3, 4 and 8. Furthermore, the MPEP states “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).” (see MPEP § 2112.01 I). In addition, since the USPTO lacks the experimental facilities to make a further determination, the burden is on the Applicant to prove the otherwise.
The difference between the reference and instant claims 1-13 is that the reference does not explicitly teach mouse osteosarcoma cell line K7M2 as the elected species of tumor; and the limitations of instant claims 7 and 9-13.
However, Ren et al teach osteosarcoma (OS) cell line K7M2 is 80% generation of spontaneous metastasis and 100% generation of experimental metastasis, for example, page 29471, Table 1.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Zeng et al and Ren et al and develop a method of inhibiting osteosarcoma metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of salvianolic acid B as a CD226 inhibitor that is configured to target CD226 molecules, and wherein the osteosarcoma can be one derived from mouse osteosarcoma cell line K7M2. It reads on mouse osteosarcoma cell line K7M2 as the elected species of tumor.
One of ordinary skilled in the art would have been motivated to combine the teachings of Zeng et al and Ren et al and develop a method of inhibiting osteosarcoma metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of salvianolic acid B as a CD226 inhibitor that is configured to target CD226 molecules, and wherein the osteosarcoma can be one derived from mouse osteosarcoma cell line K7M2, because Ren et al teach osteosarcoma (OS) cell line K7M2 is 80% generation of spontaneous metastasis and 100% generation of experimental metastasis.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Zeng et al and Ren et al and develop a method of inhibiting osteosarcoma metastasis in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of salvianolic acid B as a CD226 inhibitor that is configured to target CD226 molecules, and wherein the osteosarcoma can be one derived from mouse osteosarcoma cell line K7M2.
Conclusion
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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