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 .
DETAILED ACTION
The amendment filed April 24, 2026 in response to the Office Action of January 28, 2026 is acknowledged and has been entered.
Claims 6-12, 14 and 18 have been amended.
Claims 1-5 and 17 have been cancelled.
Claims 19-21 have been added.
Claims 6-16 and 18-21 are pending and under consideration.
In view of claim 6 amendments, the 112(b) rejection set forth in the previous Office Action on January 28, 2026 is hereby withdrawn.
In view of cancellation of claims 1-5, amendments of claim 6, and applicant’s arguments, the 112(a) Written Description rejection set forth in the previous Office Action on January 28, 2026 is hereby withdrawn.
In view of cancellation of claim 17, the 112(a) Enablement rejection set forth in the previous Office Action on January 28, 2026 is hereby withdrawn.
It is noted that the amended claim 6 limited to 21 antibodies which have written description support in the specification: MAB-7 to MAB-27 (see Table 8, Table 9, Table 15 and Table 16). Prior art does not teach or suggest the antibodies with specific sequences as recited by the amended claim 6. Thus, claims 6-16 and 19-21 are drawn to allowable subject matter.
MAINTAINED/MODIFIED REJECTION
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.
Claim 18 is 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 for inducing killing of HER-2 positive cancer cells, said method comprising administering the multispecific antibody according to claim 12 to the HER-2 positive cancer cells, wherein the multispecific antibody is a CyCAT-7, CyCAT-8, CyCAT-9, CyCAT-10, CyCAT-11, CyCAT-12, CyCAT-13, CyCAT-14, CyCAT-15, CyCAT-16, CyCAT-17, CyCAT-18, CyCAT-19, CyCAT-20, CyCAT-21, CyCAT-22, CyCAT-23, CyCAT-24, CyCAT-25, CyCAT-26, CyCAT-27”,
does not reasonably provide enablement for
“a method for inducing killing of HER-2 positive cancer cells, said method comprising administering the multispecific antibody according to claim 12 to the HER-2 positive cancer cells”.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. This is a SCOPE of ENABLEMENT rejection.
Claim 18 is drawn a method for inducing killing of HER-2 positive cancer cells, said method comprising administering the multispecific antibody according to claim 12 to the subject. Given Broadest Reasonable Interpretation (BRI), the claim encompasses a broad genus of multispecific antibody or antibody fragments and a broad genus of HER-2 positive cancer cells.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.,1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547, the court recited eight factors to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
1) the quantity of experimentation necessary, 2) the amount of direction or guidance provided, 3) the presence or absence of working examples, 4) the nature of the invention 5) the state of the art, 6) the relative skill of those in the art, 7) the predictability of the art and 8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108,427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Nature of invention and breadth of the claims:
The claim is drawn to a method for treating a broad genus HER-2 positive cancer cells with various origins with a broad genus of antibodies or antibody fragments. Claim 18, which depends on claim 12, encompasses multispecific antibodies to a broad genus of cancer associated antigens, including both known and unknown cancer associated antigens, as evidenced by claim 13. The claim may even encompass multispecific antibodies bind to antigen which is not associated with any cancers.
Level of unpredictability in the art and State of the prior art:
In the instant application, the activity of CyCAT is based on that the Fab of HER-2 binding domain bring CD3 specific VH and VL domains (see [0906] of the instant publication US 2023/0357398 A1: [0906] These results clearly demonstrate that the CD3 specific VH and VL domains comprised in each of the unpaired CyCAT polypeptides are complemented to a functional CD3 specific antibody Fv domain once both CyCAT polypeptides are bound via their Fab portion to the target antigen on the cancer cell and the two polypeptides get in close proximity. Accordingly, the newly identified CD3 specific human antibodies according to the present disclosure can be used in various approaches to efficiently re-direct T-cells to kill tumor expressing cells). Thus, the HER-2 binding domain of the CyCAT is important for redirecting T-cells to the HER2-expressing cancer cells.
In view of above, a multispecific antibody of claim 12 comprising a binding domain CD3 and another binding domain for a non-HER2 cancer associate antigen may not be able to able to induce killing of HER-2 positive cancer cells, because a multispecific antibody of claim 12 may not be able to bind to HER2 on cancer cells. Thus, one ordinary skill in the art would not be able to visualize other multispecific antibodies encompassed by the claim, which binds to a specific antigen (such as CD3 epsilon and another cancer associated antigen), would have the same activity as CyCAT antibodies described in the specification.
Direction or guidance and working examples:
MPEP § 608.01 (p) provided that within the specification, "specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. However, in view of the above, However, the specification only shows in an in vitro cell assay that co-cultivation of T-cells with a combination of CyCAT polypeptides with specificity for HER-2 and CD3 (including CyCAT-7, CyCAT-8, CyCAT-9, CyCAT-10, CyCAT-11, CyCAT-12, CyCAT-13, CyCAT-14, CyCAT-15, CyCAT-16, CyCAT-17, CyCAT-18, CyCAT-19, CyCAT-20, CyCAT-21, CyCAT-22, CyCAT-23, CyCAT-24, CyCAT-25, CyCAT-26, CyCAT-27) inducing killing of HER-2 positive SW-480 colon cancer cells (Example 11, [0905], Table 15). The specification does not disclose any results for other multispecific antibodies for inducing HER-2 positive cancer cells.
The quantity of experimentation needed:
The factors outlined in In Re Wands' mentioned above apply here, and in particular as per the MPEP 2164.01 (a): "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." It is very clear that one could not make/use this very broad invention that has no working examples in this unpredictable art without undue experimentation. Genetech Inc vs Nova Nordisk 42 USPQ 2d 1001 "A patent is not a hunting license. It is not a reward for search but compensation for its successful conclusion and patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable."
Applicant is reminded that MPEP 2164.03 teaches “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 428 F.2d 833, 166 USPQ 18, 24 (CCPA 1970) the amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly state in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order for it to be enabling. Given only lack of guidance in the specification and prior art, no one skilled in the art would accept the assertion that the claimed invention would function as contemplated or as claimed based only on the information in the specification and prior art and that known in the art at the time the invention was made.
The specification and prior art provide insufficient guidance with regard to these issues and provides insufficient working examples which would provide guidance to one skilled in the art and no evidence has been provided which would allow one of skill in the art to predict that the invention will function as contemplated or claimed with a reasonable expectation of success. For the above reasons, it appears that undue experimentation would be required to practice the claimed invention.
Due to the large quantity of experimentation necessary to test the use the broadly claimed multispecific antibodies for all HER2 positive cancer cells; the lack of direction/guidance presented in the specification regarding to multispecific antibodies other than CyCAT antibodies; and the breadth of the claims, undue experimentation would be required of the skilled artisan to use the claimed invention in its full scope.
Response to Arguments
For the 112(a) Scope of Enablement rejection to claim 18, applicant first argues: Further, with respect to claim 18, claim 6, from which claim 18 ultimately depends, has been amended to recite the antibodies of Table 10 and listed supra. Claim 18 has also been amended to recite a method for inducing killing of Her-2 positive cancer cells.
Applicant believes that the specification, and in particular Table 10 at pages 83-86 and Example 11 beginning at page 98, provide sufficient information regarding the subject matter of amended claim 18 and new claim 21 as to enable one skilled in the pertinent art to make and use the claimed invention
Applicant’s arguments have been fully considered but they are not persuasive. It is acknowledged that the specification provide support for the claimed multispecific antibodies of claim 12. As set forth above, claim 12 encompasses multispecific antibodies that also specifically bind to a cancer associated antigen and even encompass multispecific antibodies that bind to an antigen not associated with any cancer. Similarly, claim 21 encompasses a broad genus of multispecific antibodies of claim 12. Example 11 of the specification discloses only a few bispecific antibody (CYCAT: anti-HER2/CD3) which can induce killing of HER2-positive cancer cell (SW-480) (or re-directing cytotoxic activity to HER-2 positive cancer cells). Due to the large quantity of experimentation necessary to test the broadly claimed multispecific antibodies (unlimited antibodies) and/or unlimited cancer cells for the claimed method, undue experimentation would be required of the skilled artisan to use the claimed invention in its full scope.
NEW REJECTION
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.
Claim 18 is 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. This is a NEW MATTER rejection.
Claim 18 was amended after the filing date. The limitation of “inducing killing of HER-2 positive cancer cells, said method comprising administering the multispecific antibody according to claim 12 to the HER-2 positive cancer cells” in claim 18 has no clear support in the specification as originally filed. Applicants argues in the Remarks of April 24, 2026 that support for the limitation can be found in the specification for example, page 10-11 and 83-86 and Example 11 beginning at page 98.
Upon examination, pages 10-11 of the specification (file 03/21/2023) disclose modifications of IgG Fc region, related to new claims 19 and 20.
Pages 83-86 of the specification disclose the sequences of VH and VL for MAB-7 – MAB-27, related to amended claim 6.
Example 11 of the specification discloses specific CyCAT antibodies which comprise CD3 and HER-2 binding domains (Table 15). Example 5 also shows that co-cultivation of T-cells with a combination of CyCAT polypeptides with specificity for HER-2 and CD3 induced killing of HER-2 positive SW-480 target cells. However, co-cultivation of T-cells with unpaired and not combined CyCAT polypeptide with specificity for HER-2 and CD3 did not induced killing of HER-2 positive SW480 target cells.
Thus, the subject matters claimed in the amended claim 18, which encompasses binding domains to a broad genus cancer associated antigens broaden the scope of the invention as originally disclosed in the specification and claims from what was originally disclosed in the specification and claims as filed.
Claim 21 is 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 for re-directing cytotoxic activity of a T-cell to a cancer cell comprising contacting the cancer cell in the presence of a T cell with the multispecific antibody of claim 12, wherein the multispecific antibody is a CyCAT-7, CyCAT-8, CyCAT-9, CyCAT-10, CyCAT-11, CyCAT-12, CyCAT-13, CyCAT-14, CyCAT-15, CyCAT-16, CyCAT-17, CyCAT-18, CyCAT-19, CyCAT-20, CyCAT-21, CyCAT-22, CyCAT-23, CyCAT-24, CyCAT-25, CyCAT-26, CyCAT-27; and wherein the cancer cell is a HER-2 positive cancer cell”,
does not reasonably provide enablement for
“a method for re-directing cytotoxic activity of a T-cell to a cancer cell comprising contacting the cancer cell in the presence of a T cell with the multispecific antibody of claim 12.”
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. This is a SCOPE of ENABLEMENT rejection.
Claim 21 is drawn a method for a method for re-directing cytotoxic activity of a T-cell to a cancer cell comprising contacting the cancer cell in the presence of a T cell with the multispecific antibody of claim 12. Given Broadest Reasonable Interpretation (BRI), the claim encompasses a broad genus of multispecific antibody or antibody fragments and a broad genus of cancer cells.
To be enabling, the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.,1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547, the court recited eight factors to consider when assessing whether or not a disclosure would require undue experimentation. These factors are:
1) the quantity of experimentation necessary, 2) the amount of direction or guidance provided, 3) the presence or absence of working examples, 4) the nature of the invention 5) the state of the art, 6) the relative skill of those in the art, 7) the predictability of the art and 8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108,427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
Nature of invention and breadth of the claims:
The claim is drawn to a method for re-directing cytotoxic activity of a T-cell to a cancer cell. Given BRI, the claim encompasses a broad genus of cancer cells (unlimited). In addition, the claim also encompasses multispecific antibodies to a broad genus of cancer associated antigens, including both known and unknown cancer associated antigens, as evidenced by claim 13. The claim may even encompass multispecific antibodies bind to antigen which is not associated with any cancers.
Level of unpredictability in the art and State of the prior art:
In the instant application, the activity of CyCAT is based on that the Fab of HER-2 binding domain bring CD3 specific VH and VL domains (see [0906] of the instant publication US 2023/0357398 A1: [0906] These results clearly demonstrate that the CD3 specific VH and VL domains comprised in each of the unpaired CyCAT polypeptides are complemented to a functional CD3 specific antibody Fv domain once both CyCAT polypeptides are bound via their Fab portion to the target antigen on the cancer cell and the two polypeptides get in close proximity. Accordingly, the newly identified CD3 specific human antibodies according to the present disclosure can be used in various approaches to efficiently re-direct T-cells to kill tumor expressing cells). Thus, the HER-2 binding domain of the CyCAT is important for redirecting T-cells to the HER2-expressing cancer cells.
In view of above, a multispecific antibody of claim 21 comprising a binding domain CD3 and another binding domain for a non-HER2 antigen may not be able to able to redirect T-cells to cancer cells, because a multispecific antibody of claim 12 may not be able to bind to a specific antigen on cancer cells. Thus, one ordinary skill in the art would not be able to visualize other multispecific antibodies encompassed by the claim, which binds to a specific antigen (such as CD3 epsilon and another antigen), would have the same activity as CyCAT antibodies described in the specification.
Direction or guidance and working examples:
MPEP § 608.01 (p) provided that within the specification, "specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. However, in view of the above, However, the specification only shows in an in vitro cell assay that co-cultivation of T-cells with a combination of CyCAT polypeptides with specificity for HER-2 and CD3 (including CyCAT-7, CyCAT-8, CyCAT-9, CyCAT-10, CyCAT-11, CyCAT-12, CyCAT-13, CyCAT-14, CyCAT-15, CyCAT-16, CyCAT-17, CyCAT-18, CyCAT-19, CyCAT-20, CyCAT-21, CyCAT-22, CyCAT-23, CyCAT-24, CyCAT-25, CyCAT-26, CyCAT-27) re-directing cytotoxic activity of T-cells to HER-2 positive SW-480 colon cancer cells (Example 11, [0905], Table 15). The specification does not disclose any results for other multispecific antibodies for re-directing cytotoxic activity of a T cell to any other cancer cell.
The quantity of experimentation needed:
The factors outlined in In Re Wands' mentioned above apply here, and in particular as per the MPEP 2164.01 (a): "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." It is very clear that one could not make/use this very broad invention that has no working examples in this unpredictable art without undue experimentation. Genetech Inc vs Nova Nordisk 42 USPQ 2d 1001 "A patent is not a hunting license. It is not a reward for search but compensation for its successful conclusion and patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable."
Applicant is reminded that MPEP 2164.03 teaches “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 428 F.2d 833, 166 USPQ 18, 24 (CCPA 1970) the amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly state in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order for it to be enabling. Given only lack of guidance in the specification and prior art, no one skilled in the art would accept the assertion that the claimed invention would function as contemplated or as claimed based only on the information in the specification and prior art and that known in the art at the time the invention was made.
The specification and prior art provide insufficient guidance with regard to these issues and provides insufficient working examples which would provide guidance to one skilled in the art and no evidence has been provided which would allow one of skill in the art to predict that the invention will function as contemplated or claimed with a reasonable expectation of success. For the above reasons, it appears that undue experimentation would be required to practice the claimed invention.
Due to the large quantity of experimentation necessary to test the use the broadly claimed multispecific antibodies for all cancer cells; the lack of direction/guidance presented in the specification regarding to multispecific antibodies other than CyCAT antibodies; and the breadth of the claims, undue experimentation would be required of the skilled artisan to use the claimed invention in its full scope.
Conclusion
Claims 6-16 and 19-20 are drawn to allowable subject matters.
Claims 18 and 21 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHENG LU/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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