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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 17, 2025, has been entered.
The amendment filed April 17, 2025, is acknowledged and has been entered. Claims 198, 200, 218 and 221 have been amended. Claim 199 has been canceled.
Claims 198, 200-203, 206-223, and 226-237 are pending.
Claims 207, 215-217, 227 and 235-237 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention or non-elected species of invention, there being no allowable generic or linking claim.
Claims 198, 200-203, 206, 208-214, 218-223, 226 and 228-234 are under examination. Group 1 and the species of a complex with one binding moiety and one signaling domain, a modified human interferon alpha 2 (IFNa2) signaling agent having at least 95% identity with SEQ ID NO: 1 and a R149A mutation, IgG Fc chains of the Fc domain and that one or more mutations to the Fc domain results in knob-in-hole pairing along, signaling agent IL-2 or IL-15 and targeting moieties of VHH, a Fab, a Fab' and a F(ab')2 are under consideration. The species election for the targeting domain has been withdrawn.
Information Disclosure Statement
The information disclosure statement has been considered.
Grounds of Rejection Withdrawn
Applicant's amendment has obviated or rendered moot the grounds rejection set forth in the previous Office action.
New Claim Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 198, 200-203, 206, 208-214, 218-223, 226 and 228-234 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The claims are indefinite in the recitation of “a recognition domain that recognizes and/or binds to a target" in claims 198, 209, 211, 218, 229 and 231 because it is unclear how a recognition domain recognizes a target. Notably, targeting domains bind to targets, but the claims distinguish binding from recognizing such that it appears recognizing has a different scope than binding, but neither the specification nor the art appear to delineate how recognizing a target is different than binding a target. Does a recognition domain "recognize" a target by being conjugated to the antigen, does it “recognize” a target directly or indirectly, or does it “recognize” the target in some other way that differs from binding? Without knowing how recognizes differs from binds the claims cannot be construed unambiguously. Thus, the claims fail to delineate the subject matter that Applicant regards as the invention with the requisite degree of clarity and particularity to permit the skilled artisan to know or determine infringing and non-infringing subject matter and thereby satisfy the requirement set forth under 35 U.S.C. § 112, second paragraph. The dependent claims are included in the rejection as they all encompass domains that recognize a target or antigen.
Amending the claims to delete reference to “recognizes”, would obviate this rejection.
Claims 214 and 234 are also indefinite in the recitation of “wherein the chimeric protein complex comprises a second targeting moiety and/or a second signaling agent”. Notably, claims 198 and 218 recite a chimeric protein with “only one signaling agent” so it is unclear how a chimeric protein with only one signaling agent comprises a second agent. Furthermore, claims 198 and 218 recite that “the Fc domain is heterodimeric as relates to the targeting moiety and the modified signaling agent, relative to each other” but claims 214 and 234 introduce an additional targeting moiety and/or a second signaling agent, so it is unclear how such a construct is heterodimeric as relates to the targeting moiety and the modified signaling agent because there are now multiple targeting moieties and/or signaling agents
Thus, the claims fail to delineate the subject matter that Applicant regards as the invention with the requisite degree of clarity and particularity to permit the skilled artisan to know or determine infringing and non-infringing subject matter and thereby satisfy the requirement set forth under 35 U.S.C. § 112, second paragraph.
Canceling claims 214 and 234, would obviate this rejection.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 214 and 234 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In this case, claims 214 and 234 depend from claims 198 and 218, respectively that recite a chimeric protein with “only one signaling agent” which is a product claim such that these claims fail to include all the limitations of the claim upon which it depends because they remove the “only” limitation.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 218-223, 226 and 228-234 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Loew et al (WO 2017/165464 A1, IDS).
With respect to claims 218-222, 226 and 228, Loew et al discloses a heterodimeric chimeric complex comprising a targeting moiety that binds to a target and only one signaling agent, wherein the only one signaling agent is a modified signaling agent (such as an interleukin (IL-2 or IL-15) or interferon) that has reduced affinity for or activity at the signaling agent's receptor relative to the unmodified signaling agent; and an Fc domain, the Fc domain comprising two Fc chains and having one or more mutations promoting Fc chain pairing of the Fc domain (knob-in hole mutations) and having one or more mutations that reduce or eliminate one or more effector functions of the Fc domain, and/or stabilizes a hinge region in the Fc domain, wherein the Fc domain is heterodimeric as relates to the targeting moiety and the modified signaling agent, relative to each other, and wherein the targeting moiety restores the modified signaling agent's affinity for or activity at the signaling agent's receptor and further comprising a linker (see entire document, e.g., pages 4, 28, 41, 42, 72, 77, 84, 110-111, and 113-114 and 116, Figure 5A and claims).
With respect to claim 223, the Fc region can be from IgG (see page 71).
With respect to claims 229 and 233-234, chimeric protein can comprise a targeting moiety or second targeting moiety that binds the CD20 tumor antigen and (see page 103).
With respect to claim 232, the chimeric proteins can recruit immune cells to the tumor microenvironment (see pages 59-61 and 95).
With respect to claim 230, the targeting domain can be a VHH or a Fab (see pages 5, 72 and 80).
With respect to claim 231, the targeting moiety upon binding either neutralizes or does not neutralize so the molecule of the prior art would have one of these functions. Furthermore, with respect to the claimed functions in the claims, it is noted that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Therefore, as the prior art teaches products of identical structure to those claimed, the products of the prior art have these functions.
Furthermore, the Office does not have the facilities for examining and comparing Applicant's products with the products of the prior art in order to establish that the products of the prior art possesses the same material, structural, and functional characteristics as Applicant’s products. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the products to which the claims are directed are different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989).
Therefore, Loew et al deemed to anticipate the claimed products absent a showing otherwise.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 198, 200-203, 206, 208-214, 218-223, 226 and 228-234 are rejected under 35 U.S.C. 103 as being unpatentable over Loew et al (WO 2017/165464 A1, IDS) and Kley et al (WO 2017/077382 A1, IDS).
Loew et al discloses a heterodimeric chimeric complex comprising a targeting moiety that binds to a target and only one signaling agent, wherein the only one signaling agent is a modified signaling agent (such as an interleukin (IL-2 or IL-15) or interferon) that has reduced affinity for or activity at the signaling agent's receptor relative to the unmodified signaling agent; and an Fc domain, the Fc domain comprising two Fc chains and having one or more mutations promoting Fc chain pairing of the Fc domain (knob-in hole mutations) and having one or more mutations that reduce or eliminate one or more effector functions of the Fc domain, and/or stabilizes a hinge region in the Fc domain, wherein the Fc domain is heterodimeric as relates to the targeting moiety and the modified signaling agent, relative to each other, and wherein the targeting moiety restores the modified signaling agent's affinity for or activity at the signaling agent's receptor and further comprising a linker (see entire document, e.g., pages 4, 28, 41, 42, 72, 77, 84, 110-111, and 113-114 and 116, Figure 5A and claims).
Loew et al discloses the Fc region can be from IgG (see page 71).
Loew et al discloses chimeric protein can comprise a targeting moiety or second targeting moiety that binds the CD20 tumor antigen and (see page 103).
Loew et al discloses the chimeric proteins can recruit immune cells to the tumor microenvironment (see pages 59-61 and 95).
Loew et al discloses the targeting domain can be a VHH or a Fab (see pages 5, 72 and 80).
With respect to claims 211 and 231, the targeting moiety upon binding either neutralizes or does not neutralize so the molecule of the prior art would have one of these functions. Furthermore, with respect to the claimed functions in the claims, it is noted that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Therefore, as the prior art teaches products of identical structure to those claimed, the products of the prior art have these functions.
Furthermore, the Office does not have the facilities for examining and comparing Applicant's products with the products of the prior art in order to establish that the products of the prior art possesses the same material, structural, and functional characteristics as Applicant’s products. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the products to which the claims are directed are different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989).
Loew et al does not disclose a signaling agent that is a modified human interferon alpha 2 (IFNa2) signaling agent that has reduced affinity activity at IFNAR relative to unmodified human IFNa2, the modified human IFNa2 signaling agent having at least 95% identity with SEQ ID NO:1 or 2 with a R149A mutation.
Kley et al discloses chimeric protein comprising a targeting moiety a Fc fusion and a human IFNa2, having at least 95% identity with SEQ ID NO:1 or 2 with a R149A mutation (see pages 12-13, 37 and 53).
Kley et al discloses the mutation allows for the modified soluble agent to have reduced systemic toxicity, reduced side effects, and reduced off-target effects relative to unmutated, e.g. the wild type form of the soluble agent (see page 5).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to substitute human interferon IFNa2, having at least 95% identity with SEQ ID NO:1 or 2 with a R149A mutation for the interferon signaling agent of Loew et al because such a mutated human interferon IFNa2 with lower affinity would have the advantage of reduced systemic toxicity, reduced side effects, and reduced off-target effects relative to unmutated, e.g. the wild type form of the soluble agent.
In this case, making such constructs would be considered combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results. Finally, one of skill in the art would have had a reasonable expectation of success in making such constructs because the prior art evidences that genetic engineering techniques to fuse such domains into recombinant protein complexes were known in the art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references.
Claims 198, 200-203, 206, 208-214, 218-223, 226 and 228-234 are rejected under 35 U.S.C. 103 as being unpatentable over Loew et al (WO 2017/165464 A1, IDS) and Tavernier et al (WO 2013/107791 A1, IDS).
Loew et al discloses a heterodimeric chimeric complex comprising a targeting moiety that binds to a target and only one signaling agent, wherein the only one signaling agent is a modified signaling agent (such as an interleukin (IL-2 or IL-15) or interferon) that has reduced affinity for or activity at the signaling agent's receptor relative to the unmodified signaling agent; and an Fc domain, the Fc domain comprising two Fc chains and having one or more mutations promoting Fc chain pairing of the Fc domain (knob-in hole mutations) and having one or more mutations that reduce or eliminate one or more effector functions of the Fc domain, and/or stabilizes a hinge region in the Fc domain, wherein the Fc domain is heterodimeric as relates to the targeting moiety and the modified signaling agent, relative to each other, and wherein the targeting moiety restores the modified signaling agent's affinity for or activity at the signaling agent's receptor and further comprising a linker (see entire document, e.g., pages 4, 28, 41, 42, 72, 77, 84, 110-111, and 113-114 and 116, Figure 5A and claims).
Loew et al discloses the Fc region can be from IgG (see page 71).
Loew et al discloses chimeric protein can comprise a targeting moiety or second targeting moiety that binds the CD20 tumor antigen and (see page 103).
Loew et al discloses the chimeric proteins can recruit immune cells to the tumor microenvironment (see pages 59-61 and 95).
Loew et al discloses the targeting domain can be a VHH or a Fab (see pages 5, 72 and 80).
With respect to claims 211 and 231, the targeting moiety upon binding either neutralizes or does not neutralize so the molecule of the prior art would have one of these functions. Furthermore, with respect to the claimed functions in the claims, it is noted that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01. Therefore, as the prior art teaches products of identical structure to those claimed, the products of the prior art have these functions.
Furthermore, the Office does not have the facilities for examining and comparing Applicant's products with the products of the prior art in order to establish that the products of the prior art possesses the same material, structural, and functional characteristics as Applicant’s products. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the products to which the claims are directed are different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA, 1977) and Ex parte Gray, 10 USPQ2d 1922 1923 (PTO Board of Patent Appeals and Interferences, 1988 and 1989).
Loew et al does not disclose a signaling agent that is a modified human interferon alpha 2 (IFNa2) signaling agent that has reduced affinity activity at IFNAR relative to unmodified human IFNa2, the modified human IFNa2 signaling agent having at least 95% identity with SEQ ID NO:1 or 2 with a R149A mutation.
Tavernier et al discloses a composition comprising a targeting construct, wherein the targeting construct comprises: a mutated human interferon alpha 2, the mutated human interferon alpha 2 having R149A mutation and a reduced affinity for IFNAR2 as compared to the wild-type human interferon alpha 2; and a targeting moiety, the targeting moiety comprising an antibody, wherein the targeting moiety restores the reduced affinity of the mutated human interferon alpha 2 for IFNAR2 on targeted cells (see entire document, e.g., abstract, description, figures, examples and page 9).
Tavernier et al discloses the mutation allows for the modified soluble agent to have reduced systemic toxicity, reduced side effects, and reduced off-target effects relative to unmutated, e.g. the wild type form of the soluble agent (see page 2).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the claimed invention was made to substitute human interferon IFNa2, having at least 95% identity with SEQ ID NO:1 or 2 with a R149A mutation for the interferon signaling agent of Loew et al because such a mutated human interferon IFNa2 with lower affinity would have the advantage of reduced systemic toxicity, reduced side effects, and reduced off-target effects relative to unmutated, e.g. the wild type form of the soluble agent.
In this case, making such constructs would be considered combining prior art elements according to known methods to yield predictable results and simple substitution of one known element for another to obtain predictable results. Finally, one of skill in the art would have had a reasonable expectation of success in making such constructs because the prior art evidences that genetic engineering techniques to fuse such domains into recombinant protein complexes were known in the art.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references.
Conclusion
No claims are allowed. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. US 9,878,014 B2 (Tavernier et al, IDS) disclose a composition comprising a targeting construct, wherein the targeting construct comprises: a mutated human interferon alpha 2, the mutated human interferon alpha 2 having R149A mutation and a reduced affinity for IFNAR2 as compared to the wild-type human interferon alpha 2; and a targeting moiety, the targeting moiety comprising an antibody directed to Her2, wherein the targeting moiety restores the reduced affinity of the mutated human interferon alpha 2 for IFNAR2 on targeted cells.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is 571-272-9935. The examiner can normally be reached Mon-Fri
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu, can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
November 14, 2025