FINAL ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. Applicant’s response filed August 6, 2026, is acknowledged. Claims 41 and 44 have been amended to recite subject matter of previously pending claims 43 and 49, now canceled. Claims 1-40, 42-43 and 49 are canceled; and claims 51-60 are withdrawn. Therefore, claims 41, 44-48, and 50-60 are pending, with claims 51-60 withdrawn from further consideration as being drawn to the non-elected invention. Claims 41, 44-48, and 50 are therefore pending examination and currently under consideration for patentability. Note: Claim 44 is given the status identifier of “previously presented,” but also has markings indicating an amendment, and thus should properly have the status identifier of “currently amended.”
Withdrawn Objections
3. The objections to the specification are withdrawn for following reasons:
a. The objection to the specification for having trademarks that do not meet the requirements is withdrawn in light of Applicant’s amendments to the specification. See section 4 (a) of the Office Action of May 6, 2026.
b. The objection to the specification for repeating a list of claims at pages 21-24 is withdrawn in light of Applicant’s argument that: the list refers to embodiments rather than claims, and therefore the list is not a repetition of the claims. See section 4 (b) of the Office Action of May 6, 2026.
Withdrawn Rejections
4. The rejection of claims 41-48 and 50 under 35 U.S.C. § 102(a)(2) as being anticipated by Paulson (II) et al. (2009) is withdrawn in light of Applicant’s amendments. See section 9 of the Office action of May 6, 2026. Specifically, independent claim 41 has been amended to include the limitation “lipid” membrane-tethering domain (i.e., the subject matter of canceled claim 49), which is not taught by Paulson (II). The rejection of claims 42-43 are moot in view of Applicant’s cancelation of the claims.
Maintained Rejections
5. The rejection of claims 41, 44-48, and 50 under 35 U.S.C. § 112(a) (written description and enablement); and claims 41, 44-46, 48, and 50 under 35 U.S.C. 102(a)(2) as being anticipated by Paulson (I) et al. (2019) as set forth in sections 5-9 of the Office action of May 6, 2026, are maintained. The rejection of claims 42-43 are moot in view of Applicant’s cancelation of the claims.
Claim Rejections - 35 USC § 112
6. 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.
Written Description
7. Claims 41, 44-48, and 50 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 claims contain 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.
The written description rejection of record has been modified below to address “wherein the Siglec ligands are sialosides and/or analogues thereof” and repeated below for Applicant’s convenience:
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. 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.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that:
"applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
No Written Description for the Breadth of the Claims (“Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof”):
The claims are directed to cis-binding Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof.” The claims broadly encompass the genus “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof,” and only more narrowly specify that the Siglec ligands may be immunosuppressive Siglec ligands, CD-33 related Siglec ligands, or Siglec-7/9 ligands in the dependent claims. The claimed Siglec agonists must possess specific functions, including binding Siglecs in cis and agonizing the Siglecs. However, there is no structure recited in the claims that would correlate with these functions. The specification only sets forth Siglec ligands S7L and S9L (see FIG 3A) specifically as potentially having the required functions, but these two species are not sufficiently representative of such a broad genus of Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” as instantly claimed.
The specification discloses biochemical properties of Siglec agonists comprising S7L and S9L Siglec ligands at FIGs. 3-4; and evaluations of in vitro activity Siglec agonists comprising S7L and S9L Siglec ligands at FIGs. 5-11. The specification does not disclose a Siglec agonist having any other Siglec ligand; only S7L and S9L Siglec ligands are disclosed. Furthermore, the specification indicates S7L and S9L, which are synthetic Siglec ligands known in the art, were specifically chosen due to their high selectivity and affinity for the respective Siglecs (see speciation at pg. 24, lines 23-25).
The claims recite functional language of the Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof,” such as cis binding that results in Siglec agonism, however a definition by function does not suffice to define the genus because it is only an indication of what the Siglec agonist comprising Siglec ligands does, rather than what it is; therefore, it is only a definition of a useful result rather than a definition of what achieves that result. In addition, because the genus of Siglec agonists comprising Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof, is highly variable (i.e., each different Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof, would necessarily have a unique structure), the generic description of the substance is insufficient to describe the genus. Thus, the encompassed Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” have no correlation between their structure and function. To address this issue, a brief assessment of the state of the art of Siglec ligands is provided below, which shows that the genus “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” is highly variable with respect to binding properties for Siglecs.
Rillahan et al. ("Click and pick: Identification of sialoside analogues for siglec‐based cell targeting." Angewandte Chemie International Edition 51.44 (2012): 11014-11018 (cited previously); cited in the specification at pg. 24, lines 23-25) is directed to the synthesis of high affinity / selective Siglec ligands. Rillahan et al. at para. 2. Rillahan et al. designed and tested 216 synthetic Siglec ligands (e.g., sialosides and/or analogues thereof) and found that D24 (i.e., instant S9L) had the highest affinity and specificity for Siglec-9. See Rillahan et al. at FIG. 3, Supplemental Table 9. In fact, of the 216 tested Siglec agonists, only one other had at least 50% as much affinity for Siglec-9 as S9L (B24 has 62.6% affinity compared to D24 / S9L). See Rillahan et al. at Supplemental Table 9. Rillahan et al. therefore demonstrates it is very unpredictable how well a “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof” will bind to a Siglec, and significant experimentation is required to determine Siglec ligands suitable for use with a Siglec agonist that binds Siglecs in cis and thereby agonizes the Siglecs.
Neither the art nor the specification provides a sufficient representative number of Siglec ligand species that bind to Siglecs with sufficient specificity and affinity to effectuate cis Siglec agonism to meet the written description requirement for instant claims directed to Siglec-7/9 ligands in general, let alone to meet the written description requirement for instant claims directed to Siglec agonists comprising the broad genus “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof.”
It is therefore unknown how the genus of Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” would bind to Siglecs in cis and agonize the Siglecs. Applicant has not shown possession of a representative number of species that have the claimed function(s). The specification therefore provides insufficient written description to support the genus of Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” encompassed by the claims. Given all of the above, Applicant does not have written description for Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof.”
The cited reference therefore demonstrate that Applicant is not in possession of: Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof;” Applicant is in possession of: Siglec agonists comprising S9L or S7L.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Applicant’s Arguments
Applicant argues that: amending claim 41 to recite that the Siglec ligands are “sialosides and/or analogues thereof” renders the claim-recited genus of Sigle ligands as a structurally defined class that cannot be characterized as a functional genus. Applicant points to page 11 of the specification to support the notion that “sialosides and analogues thereof” are an art-recognized structural class; that information that is well known in the art need not be described in detail in the specification; and that a skilled artisan would have been able to identify additional members of the genus by employing common tools. Applicant points to Rillahan et al. (2012; of record) and Blixt et al. (2008; cited in IDS of August 8, 2026) as evidence that additional representative species of Siglec ligands that are sialosides and/or analogues were well known or readily ascertainable from the art.
Response to Arguments
Applicant’s arguments have been fully considered but they are not deemed persuasive.
The Office disagrees that the skilled artisan would have been able to readily identify additional members of the genus of Siglec ligands that are sialosides and/or analogues thereof—and that sufficiently bind Siglecs as required by the claims—to establish possession of the instantly claimed genus of Siglec ligands. Neither Rillahan et al. nor Blixt et al. show sufficient additional species of the Siglec ligands that may work with the claimed invention. Therefore, the claims still recite a functional genus regardless of the art’s use of the term “sialosides and/or analogues thereof.”
For example, Rillahan et al. designed and tested 216 synthetic Siglec ligands and found that D24 (i.e., instant S9L) had the highest affinity and specificity for Siglec-9. See Rillahan et al. at FIG. 3, Supplemental Table 9. In fact, of the 216 Siglec agonists tested, only one other had at least 50% as much affinity for Siglec-9 as S9L (B24 has 62.6% affinity compared to D24 / S9L). See Rillahan et al. at Supplemental Table 9. Rillahan et al. therefore demonstrates it is very unpredictable how well a sialosides and/or analogue thereof will bind to a Siglec, and that significant experimentation is required to determine Siglec ligands suitable for use with a Siglec agonist that binds Siglecs in cis and thereby agonizes the Siglecs. This is because: Rillahan et al.—despite developing a high-throughput assay to identify Siglec ligands—was unsuccessful in identifying more than just a few Siglec ligands that may work with the instantly claimed invention after testing hundreds of candidates. Therefore, the skilled artisan would not have been able to readily identify additional members of the genus of Siglec ligands instantly claimed based on what was known in the art or disclosed in the instant specification.
This is further supported by Blixt et al., also cited by Applicant, which concludes at the last sentence that their disclosure allows for “subsequent screening for high affinity ligands of Siglecs and other sialoside binding GBPs.” This is merely an invitation for the skilled artisan to do the necessary work to identify suitable Siglec ligands, and further evidences that the information is not well known in the art. In fact, Rillahan et al., discussed above, foreshadows the distinct possibility that no other suitable Siglec ligands may be ascertainable by a person skilled in the art even with extreme experimentation, since Rillahan et al. tested so many but identified so few having sufficient Siglec binding activity.
The MPEP at § 2163.II.A.3(a) addresses this issue and instructs that: “An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described.").
Accordingly, Applicant lacks possession of the scope of Siglec ligands instantly claimed.
Enablement
8. Claims 41, 44-48, and 50 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 Siglec agonists comprising Siglec ligands S7L and S9L, does not reasonably provide enablement for Siglec agonists comprising the genus “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof.” 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 use the invention commensurate in scope with these claims.
The enablement rejection of record has been modified below to address “wherein the Siglec ligands are sialosides and/or analogues thereof” and repeated below for Applicant’s convenience:
It is noted that MPEP 2164.03 teaches that “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, 427 F.2d 833, 839, 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 stated 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 to be enabling.”
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “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, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)):
1) nature of the invention;
2) the breadth of the claims;
3) the state of the prior art;
4) the level of one of ordinary skill;
5) the level of predictability in the art;
6) the amount of direction or guidance provided by the inventor;
7) the existence of working examples; and
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
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. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(2) The breadth of the claims:
The claims are drawn to cis-binding Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” that bind to Siglecs in cis and agonize the Siglecs. The dependent claims further recite the Siglec ligands may be immunosuppressive Siglec ligands, CD-33 related Siglec ligands, or Siglec-7/9 ligands.
The claims are therefore broad and encompass Siglec agonists having any type of “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof.”
(5) The predictability or unpredictability of the art:
The state of the art indicates it is very unpredictable how well members of the genus “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof” will bind to Siglecs and thereby effectuate cis agonism of the Siglec.
Rillahan et al. ("Click and pick: Identification of sialoside analogues for siglec‐based cell targeting." Angewandte Chemie International Edition 51.44 (2012): 11014-11018; cited in the specification at pg. 24, lines 23-25) is directed to the synthesis of high affinity / selective Siglec ligands. Rillahan et al. at para. 2. Rillahan et al. designed and tested 216 synthetic Siglec ligands and found that D24 (i.e., instant S9L) had the highest affinity and specificity for Siglec-9. See Rillahan et al. at FIG. 3, Supplemental Table 9. In fact, of the 216 tested Siglec agonists, only one other had at least 50% as much affinity for Siglec-9 as S9L (B24 has 62.6% affinity compared to D24 / S9L). See Rillahan et al. at Supplemental Table 9. Rillahan et al. therefore demonstrates it is very unpredictable how well a “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof” will bind to a Siglec, and significant experimentation is required to determine Siglec ligands suitable for use with a Siglec agonist that binds Siglecs in cis and thereby agonizes the Siglecs.
The cited reference therefore demonstrates that effective agonism of a Siglec with members of the genus “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof” in cis is highly unpredictable. Therefore, without actually performing the required experiments, it is unpredictable which members of the instantly claimed genus of Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” can bind to Siglecs in cis and agonize the Siglecs.
6) the amount of direction or guidance provided by the inventor:
The specification discloses biochemical properties of Siglec agonists comprising S7L and S9L Siglec ligands at FIGs. 3-4; and evaluations of the in vitro activity Siglec agonists comprising S7L and S9L Siglec ligands at FIGs. 5-11. The specification does not disclose a Siglec agonist having any other Siglec ligand; only S7L and S9L Siglec ligands are disclosed. Furthermore, the specification indicates S7L and S9L, which are synthetic Siglec ligands known in the art, were specifically chosen due to their high selectivity and affinity for the respective Siglecs (see speciation at pg. 24, lines 23-25).
The specification therefore only discloses Siglec agonists comprising optimized S7L and S9L Siglec ligands. Given the evidence above, one of skill in the art could not reasonably extrapolate the instant findings regarding Siglec agonists comprising S7L or S9L to Siglec agonists comprising genus “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof,” without undue experimentation. It would also be undue experimentation to confirm which of the 100s of Siglec ligands encompassed by the claims could bind to Siglecs in cis and thereby agonize the Siglecs.
8) the quantity of experimentation needed to make or use the invention:
It would be undue experimentation to make or use the invention encompassed by the breadth of the claims because 100s of Siglec agonists comprising “Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof” would need to be made and evaluated for functionality; Applicant has only made and evaluated two Siglec agonists comprising optimized Siglec ligands (i.e., S7L and S9L) that Rillahan et al. shows are not representative of the genus “Siglec ligand.”
In conclusion, the claimed invention does not provide enablement for Siglec agonists comprising genus “Siglec ligand, wherein the Siglec ligands are sialosides and/or analogues thereof;” the claimed invention provides enablement for Siglec agonist comprising S7L or S9L. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Applicant’s Arguments
Applicant argues that: (i) the breadth of the claims has been sufficiently focused by specifying the Siglec agonists are sialosides and/or agonists thereof; (ii) Siglec-sialoside binding chemistry was a mature area of glycobiology as of the priority date of the instant application; (iii) the person of ordinary skill in the art is a glycochemist with working knowledge of sialoside structure-activity relationship and standard Siglec-binding assays; (iv) that Rillahan (2012) supports the proposition that high affinity sialosides and/or analogues thereof may predictably be identified by using the high-affinity screening approach taught therein; (v) that the synthesis scheme taught in Example 1 is generalizable to make additional Siglec ligands; (vi) and that the high throughput / rapid identification approaches taught by Rillahan and Blixt render the instantly claimed genus of sialosides and/or analogues thereof readily available to a person of ordinary skill in the art.
Response to Arguments
Applicant’s arguments have been fully considered but they are not deemed persuasive.
The Office disagrees with points (i)-(iv) and (vi) because: although the specification may be enabling for the making of sialosides and/or analogues thereof in general (i.e., point v), neither the specification nor the art indicate which species of sialosides and/or analogues thereof to make and use with the instantly claimed invention, other than S9L and S7L.
Rillahan et al. and Blixt et al. demonstrate that the Siglec-sialoside binding chemistry was not a sufficiently mature area of glycobiology to allow the prediction of sialosides and/or analogues thereof that may work with the claimed invention, without undue experimentation.
For example, Rillahan et al. designed and tested 216 synthetic Siglec ligands and found that D24 (i.e., instant S9L) had the highest affinity and specificity for Siglec-9. See Rillahan et al. at FIG. 3, Supplemental Table 9. In fact, of the 216 Siglec agonists tested, only one other had at least 50% as much affinity for Siglec-9 as S9L (B24 has 62.6% affinity compared to D24 / S9L). See Rillahan et al. at Supplemental Table 9. Rillahan et al. therefore demonstrates it is very unpredictable how well a sialosides and/or analogue thereof will bind to a Siglec, and that significant experimentation is required to determine Siglec ligands suitable for use with a Siglec agonist that binds Siglecs in cis and thereby agonizes the Siglecs. This is because: Rillahan et al.—despite developing a high-throughput assay to identify Siglec ligands—was unsuccessful in identifying more than just a few Siglec ligands that may work with the instantly claimed invention after testing hundreds of candidates. Therefore, the skilled artisan would not have been able to readily identify additional members of the genus of Siglec ligands instantly claimed based on what was known in the art or disclosed in the instant specification without undue experimentation.
This is further supported by Blixt et al., also cited by Applicant, which concludes at the last sentence that their disclosure allows for “subsequent screening for high affinity ligands of Siglecs and other sialoside binding GBPs.” This is merely an invitation for the skilled artisan to do the necessary work to identify suitable Siglec ligands, and further provides evidence that the information is not well known in the art. In fact, Rillahan et al., discussed above, foreshadows the distinct possibility that no other suitable Siglec ligands may be ascertainable by a person skilled in the art even with extreme experimentation, since Rillahan et al. tested so many but identified so few having sufficient Siglec binding activity. Accordingly, neither the speciation nor the art teach the skilled artisan how to make and use a sufficient number of species of sialosides and/or analogues thereof that may work with the claimed invention. The speciation therefore only enables the use of cis binding Siglec agonists employing S9L or S7L sialosides and/or analogues thereof.
Claim Rejections - 35 USC § 102
9. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 41, 44-46, 48, and 50 are rejected under U.S.C. 102(a)(2) as being anticipated by Paulson (I) et al. (US20190151444A1, published May 23, 2019; cited previously).
The anticipation rejection of record has been modified below to address instantly amended claim 41 and repeated below for Applicant’s convenience:
Claim 41 is drawn to a cis-binding Siglec agonist comprising: a glycopeptide scaffold bearing Siglec ligands, wherein the Siglec ligands are sialosides and/or analogues thereof; and a lipid membrane-tethering domain, adapted to insert into the plasma membrane of a cell
Claim 44 is drawn to the Siglec agonist of claim 41, wherein the glycopeptide scaffold comprises from 2 to 50 Siglec ligands.
Claim 45 is drawn to the Siglec agonist of claim 41, wherein the Siglec ligands comprise immunosuppressive Siglec ligands.
Claim 46 is drawn to the Siglec agonist of claim 45, wherein the Siglec ligands comprise ligands for one or more CD33-related Siglecs.
Claim 48 is drawn to the Siglec agonist of claim 46, wherein the Siglec ligands comprise Siglec-7 ligands.
Claim 50 is drawn to a pharmaceutical composition comprising: the Siglec agonist of claim 41; and a pharmaceutically acceptable carrier.
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740
530
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Paulson (I) et al. at FIG. 5A (above) disclose a liposome carrier (i.e., a “scaffold”) bearing five CD33-L Siglec agonist ligands binding to three membrane-associated CD33 Siglecs in cis. Note: the binding is in cis because the ligands are binding Siglecs on the same cell. Paulson (I) et al. disclose that the Siglec agonist may comprise polymer or glycopolypeptide scaffolds—see e.g., Paulson (I) et al. at para. [0151]-[0152] describing Siglec ligands displayed/linked on carriers, and that the carriers can be polyamino-based; and at para. [0163] describing Siglec ligands as glycans; Note: glycans (e.g., Siglec ligands) displayed/linked to a polyamino/polypeptide scaffold renders a glycopolypeptide scaffold. Paulson (I) et al. disclose the synthesis of “sialoside derivative” ligands at para. [0214] (i.e., “wherein the Siglec ligands are sialosides and/or analogues thereof”). Paulson (I) et al. further disclose a lipid membrane tethering domain (see e.g., Paulson (I) et al. at para. [0058]—the third sugar of the Siglec ligand may comprise lipid or pegylated lipid to insert into a liposome scaffold, and which will also necessarily be insertable into the plasma membrane of a cell (claims 41, 44, 46, and 49). Paulson (I) et al. also disclose that the Siglec ligands may effectuate immunosuppression (see e.g., Paulson (I) et al. at para. [0163] (claim 45); that the Siglec ligands may be Siglec-7 ligands (see e.g., Paulson (I) et al. at claim 15 (claim 48); and that the Siglec agonist may be comprised in a pharmaceutical composition with pharmaceutically acceptable carrier (see e.g., Paulson (I) et al. at para. [0174] (claim 50). Accordingly, Paulson (I) et al. anticipates claims 41, 44-46, 48, and 50.
Applicant’s Arguments
A. Applicant argues that: the most relevant disclosure of Paulson (I) is a lipid-based nanoparticle decorated with Siglec ligands, but the nanoparticle does not: (i) constitute a glycopolypeptide scaffold bearing Siglec ligands; or (ii) comprise a lipid membrane-tethering domain adapted to insert into the plasma membrane of a cell as required by the instantly amended claims. Applicant cites MPEP § 2131 for its guidance that a claim is anticipated only if each and every element set forth in the claim is found, either expressly or inherently described, in a single prior art reference.
B. Applicant further argues that because of the alleged structural differences—and pointing to FIG. 1 of Paulson (I)—that the nanoparticle of Paulson (I) is not a cis-binding Siglec agonist as required by the instant claims, but rather it is a trans-binding Siglec agonist.
Response to Arguments
A. Applicant’s arguments have been fully considered but they are not deemed persuasive.
As noted by Applicant, the MPEP’s guidance on anticipation requires a single reference to disclose each and every limitation of the claim. As set out in the rejection above, Paulson (I) does teach each and every limitation of the indicated claims, and it matters not if a preferred embodiment of Paulson (I) differs in some aspect from the claimed invention.
It is also noted that claim 41 has been amended to recite a lipid membrane-tethering domain adapted to insert into the plasma membrane of a cell. The specification does not define the term “adapted,” and so it is afforded its broadest reasonable interpretation: “adapted” means the lipid membrane-tethering domain is capable of inserting into the plasma membrane of a cell. Accordingly, any lipid membrane-tethering domain that is capable of inserting into the plasma membrane of a cell reads on this feature.
Therefore, although the preferred embodiment of Paulson (I) has a liposome scaffold, Paulson (I) also teaches the scaffold can instead be a glycopolypeptide; and although Paulson (I) teaches the lipid membrane-tethering domain adapted to insert into the plasma membrane of a liposome, it will also necessarily be capable of inserting into the plasma membrane of a cell since, e.g., Paulson (I) explains that liposomes comprise a lipid bilayer (the same as cells) at para. [0156]. Therefore, a person of ordinary skill in the art would recognize that a lipid membrane-tethering domain adapted to insert into the plasma membrane of a liposome will also necessarily result in a lipid membrane-tethering domain adapted to / capable of inserting into the plasma membrane of a cell as instantly claimed.
Furthermore, the instant claims recite that the agonist comprises a lipid membrane-tethering domain adapted to insert into the plasma membrane of “a” cell. This indicates the lipid membrane-tethering domain may be adapted to insert into the plasma membrane of any cell and does not limit the claimed agonist to one that that specifically inserts into the same cell bearing the Siglecs to effectuate cis binding—such as demonstrated in the instant specification. It should also be noted that Paulson (I) does not disclose the feature: agonist having a lipid membrane-tethering domain adapted to insert into the plasma membrane of the same cell bearing the Siglecs.
The MPEP at § 2123 I and II also addresses the issue of non-preferred embodiments in an anticipatory reference and instructs that: "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)); and “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).”
Accordingly, Paulson (I)’s preferred embodiment does not diminish the remainder of Paulson (I)’s disclosure.
B. With regards to the “cis binding” limitation, the Office is of the opinion that FIG. 5A of Paulson (I) shows its invention binding to Siglec in cis because: the Siglec ligands of Paulson (I) are shown to be binding to three Siglecs presenting on the same cell, and therefore the binding is in cis. Accordingly, Paulson (I) discloses each and every limitation of 41, 44-46, 48, and 50, thereby anticipating the claims.
Conclusion
10. No claim is allowed.
11. THIS ACTION IS MADE FINAL. 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.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON R SCHWECHTER whose telephone number is (571)272-1270. The examiner can normally be reached on M-Th from 7 to 4 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number 20857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRANDON R SCHWECHTER/
Examiner, Art Unit 1674
/VANESSA L. FORD/ Supervisory Patent Examiner, Art Unit 1674
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