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 .
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.
DETAILED ACTION
Election/Restrictions
This action is in response to claim amendments filed 8/11/25. Claims 17, 19-21, and 24-28 are pending.
Applicant’s election without traverse of Group I and the species of CXCR4 antagonizing agent and Plerixafor in the reply filed on 8/11/25 is acknowledged. After examination, the species election is withdrawn.
Claims 17, 19-21, and 24-28 are under examination.
Drawings
The drawings are objected to because:
In figures 1-3, the scale labels (numbers) on both the x and y axis for the four graphs on the left are illegible.
In figure 6, the scale labels on the x and y axis for the Hoechst graphs are illegible.
In figures 7A-7D, the scale labels on the x and y axis for the top row is illegible.
Figure 11 is described in the brief description of the drawings as showing blue, green, and red. However, no color drawings have been submitted. Thus, the submitted drawing fails to show the details set forth in the description.
In figures 12-13, the scale labels on both the x and y axis for the four graphs on the left are illegible.
In figure 15, the lines cannot be distinguished. In the legend of the top graph, it appears that “no treatment” might be a diamond and the other two groups might be circles, yet the graph appears to use circles for all three groups. The bottom graph appears to use circles for every group on the graph and in the legend. The color for the groups and lines in both graphs appears to be the same shade of grey and so cannot be distinguished.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
It is noted that VCAM1 is a synonym for CD106.
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 17, 19-21, and 24-28 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 17 recites “diabetes mellitus or a disease, disorder, and/or symptom associated with diabetes mellitus”. A plain reading of this claim language would suggest that the claim is directed to either 1) treatment of diabetes mellitus (DM) or 2) treatment of a symptom/disorder caused by the diabetes mellitus (“associated with”). However, this interpretation is undermined by dependent claim 24. Claim 24 states the disorder/symptom is “a diabetic complication”. The only use of this phrase in the specification is discussion of disorders/symptoms in subjects having DM. In order to comply with §112(d), this must be a further limitation. The further limitation here would be that the disorder/symptom is caused by DM (the disorder is a complication of DM) meaning that claim 17 must encompass disorders/symptoms “associated with”, but not comorbid with, DM or diabetes. This renders the term “associated” indefinite. Where a subject has DM, the associated conditions, e.g., neuropathy, Alzheimer’s disease, skin symptoms, or cancer, are caused by the comorbid DM; see p.32-33 for a list of examples of associated conditions. When the subject does not have DM, i.e., these are symptoms “associated” with diabetes but not diabetic complications, then these symptoms clearly cannot be caused by a comorbid DM in which case the broadest, reasonable interpretation is that these diseases, conditions, and symptoms are known to be associated with DM—as in, subjects with DM are known to have a higher incidence of these conditions than those without DM—but include these conditions even where they are not caused by DM. For example, p.32 of the specification lists “leg cramp” as an associated symptom. The BRI of the claim would therefore include treating and preventing leg cramp—which is a symptom associated with DM—in subjects that do not have DM (because the leg cramp is not a diabetic complication) but instead have leg cramps caused by exercise or electrolyte imbalances (Young; form 892). The instant specification does not explicitly redefine the claimed phrase but notes that the phrase “associated” can include any such condition “associated”. In other words, the specification does not clarify if “associated” means DM must be comorbid/causative or if the condition merely needs to be known to have some association with DM irrespective of why a particular subject has the condition.
The term “abnormal” is a relative term. The claim recites reducing or eliminating “an abnormal hematopoietic stem cell (HSC)” but does not define the term “abnormal”. An HSC may be abnormal in multiple ways; see specification p.2 L30-34 where the cell is abnormal by not expressing CD106 at a “normal” level and p.3 L10-14 where the cell is abnormal by not expressing TNFα protein at a “normal” level. It is unclear if the cell must be abnormal in some specific way, if being abnormal in any particular aspect is sufficient, or if the cell must be abnormal in a combination of aspects disclosed by the specification. Where an HSC does not express “normal” levels of CD106 but expresses “normal” levels of TNFα, the cell is both normal and abnormal depending on what is being evaluated, leading to confusion over the scope of the claims.
The same applies to recitations of “normal” in e.g., claim 19. Expression and function at a “normal” level requires some definition of what level is “normal”. Looking at figure 14 of the instant application, CD106 levels in both DM and non-DM significantly overlap meaning there is no clear value that would distinguish “normal” from “DM” levels. Even just looking at the “non-DM” group, which in some cases would be interpreted to be the “normal” levels, there appears to be a range of levels which might be considered normal depending on the particular cutoff or group being compared. A CD106 expression of “1” appears to be artificially set as the average result of the “healthy human subjects” examined in this particular application (“relative amount”; p.29). Taking a different group of healthy human subjects would yield a different amount that might have an average higher or lower than the instant “1” and, moreover, could not be fairly compared to the instant result since any amount could be adjusted such that it is set at a relative value of “1”. Thus, comparison to a “normal” amount is entirely relative to the group being set as “normal”, the subjects which are part of that group, and how one chooses to report the results. This does not fairly warn others as to the meets and bounds of a “normal” level, meaning others cannot fairly interpret the metes and bounds of a cell which does not function at a “normal” level. This renders the phrase indefinite.
Claim 19 also recites the phase “is not expressed and/or does not function at a normal level”. This phrase confuses the metes and bounds of the claim. Where the choices are listed in the alternative, the meaning is clear: the gene/protein 1) does not function at a normal level OR 2) is not expressed. Where the choices are not alternatives, the claim reads the gene/protein 1) does not function at a normal level AND 2) is not expressed. If the gene or protein is not expressed, it is unclear how one could determine the gene or protein is also not functioning at normal levels. If this were the only consideration, then an ordinary, reasonable reading of the claim would be that the gene/protein is not functioning at a normal level because the gene/protein is not being expressed and so cannot function. However, this is further confused by claim 20: wherein the expression which is not at a normal level is overexpression. First, this phrase lacks antecedent basis. Claim 19 lists two options: 1) does not function at a normal level and 2) not expressed. There is no earlier recitation of expression being at a “not a normal level”. For the purposes of interpretation, not being expressed could be presumed to also be at a non-normal level. However, not being expressed cannot also be “overexpression”. Thus, “the expression which is not at a normal level is overexpression” cannot be referring to the earlier recitation of “is not expressed”. Another interpretation is that “the expression” is meant to refer to “does not function” as both of these phrases are modified by “at a normal level”. However, this also does not make sense. Since the claim is “and/or”, this would lead the explicit embodiment of “is not expressed AND is overexpression”, which, as above, are two states which are mutually exclusive. It is also unclear if the “not” is meant to be replaced by “overexpression” or modified by it. A plain reading of the claim is that the choice offered in claim 20 defines the expression/function, and so would read “is not expressed and/or [is not overexpression]”. While this would allow for “not expressed” to be a valid choice—since not expressed is not overexpression—it remains unclear if this means that “normal levels” would be allowed, since those levels are also not overexpression. However, such an interpretation would run contrary to the ordinary meaning in the claims of “does not function at a normal level”. It is unclear if Applicant is attempting to act as their own lexicographer to redefine a term contrary to its ordinary meaning or if there is some other interpretation intended by Applicant. On the whole, this combination of claims 19 and 20 make the scope of the claim confusing such that it is entirely unclear what the intention of the claim scope is.
Claim 21 recites the limitation "the suppressing agent". There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 17. Claim 17 recites “reduces” and “eliminates” an abnormal HSC but does not recite “suppression” or “a suppressing agent”.
Claims 21 and 28 recite “at least one selected” but does not answer the question: at least one what? Compare this to, e.g., claim 27 which states “at least one agent”, clearly indicating what is being selected.
Therefore, claims 17, 19-21, and 24-28 are indefinite.
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.
Claims 17, 19-21, and 24-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims recite:
An agent that reduces or eliminates an abnormal HSC
A stem cell migration agent
Functional equivalents of CD106
A functional variant of an anti-CD106 antibody
CXCR4 antagonizing agent
CXCR2 stimulating agent
EGFR inhibiting agent
G-CSF agent
See MPEP §2163(I)(A) which states:
"The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
See also:
Under MPEP §2163, elements “auxiliary to the invention must have a corresponding written description only so specific as to lead one having ordinary skill in the art to that class of compounds. Occasionally, a functional recitation of those known compounds in the specification may be sufficient as that description”.
It is clear that several elements of the claims are claimed by function alone. These genera must be analyzed to determine if claiming these elements solely by their hoped-for function is sufficient to meet the written description requirement.
In the case of “G-CSF agent”, G-CSF is a well-known protein. There is no modifier, e.g., “G-CSF inhibiting” or “G-CSF stimulating”, so the “agent” is clearly referring to the G-CSF protein itself. This meets the written description requirement.
The other functionally claimed genera in claim 27 are considered auxiliary to the invention. The invention as set forth in claim 17 is the combination of an agent that reduces/eliminates abnormal HSC and a stem cell migration agent. The genera in claim 27 themselves are known in the art and direction to this “class” of compounds defined by their function is deemed sufficient to claim the genera of claim 27 as well as “cell migration agent” (which is not auxiliary) in claim 17.
However, “agent that reduces or eliminates an abnormal HSC”, as well as “equivalents” and “variants” do not meet the written description requirement. First, the genus of “agent that reduces or eliminates an abnormal HSC” is considered part of the invention itself and not subject to the “auxiliary” exception. While this genus is not claimed as a “suppressing agent”, such agents will be considered for the claimed genus. In such case, the specification teaches CD106 antibodies, TNFα antibodies, HDAC inhibiting agents (such as trichostatin A), suppressing agents which target CD34, and suppressing agents which target proinsulin.
One means of providing adequate written description and evidence of possession of a claimed genus is through providing sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In this case, the specification discloses certain species—generally themselves functionally defined genera—but does not correlate any particular shared structure within these species to the genus as a whole responsible for the required function; there is no identification of any particular structure that must be conserved throughout the genus. Rather, no such structure would be expected to exist since the targets themselves vary significantly and there is no known single structure that will suppress a cell by targeting all of CD106, CD34, HDAC, proinsulin, etc.
In a second way, the specification might provide a representative number of species for the claimed genus that would convey to the artisan possession of the whole genus. However, in this case, the species disclosed to not represent the full breadth of all possible members of the genus.
As above, the species representative of the genus are generally also functionally defined genera and so do not represent the structures/species required of the genus. To the extent that some specific agent is disclosed, the genus of HDAC inhibitors is well described by a representative number of species (specification p.72). The others are limited to “antibody” without providing explicit examples of members of those genera. In contrast, the specification defines “suppressing agent” as “an agent that suppresses the target cell by any means” (p.35). Clearly, the definition is meant to encompass all possible means of achieving the end result while disclosing at most those specific agents known to applicant (in the case of HDAC inhibitors) or a general allegation that the agent is an antibody of some kind “or equivalent”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of 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). As discussed above, the artisan cannot envision the detailed chemical structure of the encompassed genus of possible “agents” which are claimed by no more than their desired function of eliminating or reducing an abnormal HSC. This is not a recognized “class” of molecule and so does not provide adequate guidance to the skilled artisan with respect to identity of “an agent that suppresses the target cell by any means”, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
Next, the claims also recite anti-CD106 antibodies “or a functional variant thereof”. Guidance regarding this phrase is found in the specification on page 41: substance resulting from altering the
molecule while maintaining the function of the molecule. The specification provides certain examples, such as conjugation to labels or fragments that keep only the functional portion of the molecule. In this sense, written description is met. Adding additional elements such as labels can be envisaged by the skilled artisan; while these would not generally be considered “variants” of an antibody, Applicant is allowed to be their own lexicographer and this example is illustrative. In the same way, antibody fragments which preserve the binding function are also well-known, such as scFV, Fab, etc.
However, the next paragraph (p.41 L23-32) creates a deficiency in the phrase under written description. The hyper variable regions (HVRs), i.e., complementarity determining regions (CDRs) of an antibody, are well established in the art as the portion of the binding region which imparts the specificity of an antibody and these regions are made of amino acids. The specification makes clear that a “functional variant” includes an arbitrary number of amino acid insertions, deletions, and substitutions so long as the function is preserved. There is no way to a priori look at an antigen sequence (such as CD106) and envisage the combination of six CDRs that will bind that antigen nor is there any way to look at a specific parent antibody and envisage the substitutions, insertions, or deletions in regions such as the CDRs which will predictably preserve the required function. First, even highly related CDRs may not bind the same target. See for example Kussie (cited on form 892) who demonstrates that a single amino acid change in the heavy chain of an antibody which binds p-axophenylarsonate (Ars) completely abrogates the ability of the antibody to bind Ars but adds the functionality of binding the structurally related p-azophenylsulfonate (e.g., abstract). Second, even when provided with several related antibodies that bind the desired target, this does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding properties. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions (p.7) and which bound the target, but in no way allowed one to envisage the unique structure of Centocor' s antibodies which bound the same target but shared only 50% sequence similarity (see table on page 11). Thus, the art recognizes that the CDRs define the binding properties of an antibody and that even single amino acid changes to this region can completely abrogate the binding specificity of an antibody. Information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed. While the art may have knowledge of a certain number of antibodies that bind, e.g., CD106, the instant description as well as the art at the time of filing lacks an adequate description such that the skilled artisan could envisage all possible “variants” of the amino acid sequences in those antibodies which would preserve the required function. Thus, taken as a whole, the specification lacks adequate description of all possible agents within the breadth of “functional variant” of antibodies.
This is further exacerbated by the target. The claims do not limit the abnormal HSCs to expressing (or not expressing), e.g., CD106. Where an HSC expresses CD106, known antibodies against CD106 would at least be expected to function. The instant specification makes clear that the claimed “functional equivalent thereof” encompasses mutants or variants, such as amino acid sequence variants (specification p.41). Thus, the abnormal HSCs are characterized to encompass any and all mutants and variants—known and unknown—which might somehow interact with the claimed suppressing agents. While one cannot look at a known antigen and predict the antibody which binds it, one certainly cannot predict which mutants and variants might lead to an “abnormal” HSC nor the antibodies which bind this unknown target.
Therefore, claims 17, 19-21, and 24-28 do not meet the written description requirement.
Claims 17, 19-21, and 24-28 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 treating DM where the abnormal HSCs overexpress CD106+, does not reasonably provide enablement for treating DM where the HSCs are CD106-, are at non-DM CD106 levels, or where the CD106 does not function at a normal level. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: 1) nature of the invention, 2) breadth of claims, 3) amount of direction or guidance by the inventor, 4) relative skill of those in the art, 5) level of predictability in the art, 6) state of the prior art, 7) existence of working examples, and 8) quantity of the experimentation needed to make or use the invention. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The nature of the invention is treating DM by inhibiting/suppressing abnormal HSCs. The breadth includes explicitly where the abnormal HSC has the gene or protein for CD106 “is not expressed”.
The guidance in the specification is that CD106+ HSCs are the causative factor for DM. The specification teaches HSCs express CD106 at a “normal” level in non-DM mice (p.86 L22-24) and this expression is increased in STZ-DM mice. The specification states “It is considered that [HSCs] having these features [increased CD106 expression] cause the appearance of the feature of diabetes mellitus as a chronic disease”; p.86 L29-31). Thus, the specification makes it clear that the HSCs must overexpress CD106 in order to be a therapeutic target. The instant specification does not disclose any working examples where CD106- HSCs were targeted to treat DM. The skilled artisan would not predict such a method would function as the specification discloses that the CD106 must be both expressed and expressed at increased levels in order to recapitulate the disease. Additionally, there would be no reason to expect suppressing agents such as anti-CD106 antibodies would function in the absence of the CD106 ligand.
Dependent claims do not clearly correct this deficiency. Claim 19 explicitly claims the embodiment of CD106 is not expressed and so this embodiment must be included in claim 17 and dependent claims thereof. Claim 20 is included because the claim is indefinite to the point of not being able to make a reasonable interpretation of the scope of that claim (see above). However, as noted in the header of this rejection, where the abnormal HSCs express CD106 at levels above non-DM subjects, such an embodiment is considered enabled.
Therefore, claims 17, 19-21, and 24-28 are not enabled for their full scope.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 17, 19-21, and 24-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-3, 5-6, 8-12, 20-21, 23-30, and 32 of copending Application No. 18548023 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 17 is a method of treating diabetes mellitus comprising administering 1) an agent which reduces/eliminates HSCs and 2) a stem cell migration agent. Reference claim 23 claims “a method for treating diabetes mellitus” comprising “administering…a suppressing agent for an abnormal [HSC]…in combination with a stem cell migration agent”. Thus, reference claim 23 anticipates the instant claim. Note that reference claim 20 is also anticipatory of instant claim 17, differing only in specifying the “suppressing agent” is an HDAC inhibitor.
Instant claim 19 requires the abnormal HSC does not express CD106. Reference claim 6 has the same limitations for the abnormal HSC and so anticipates the claim.
Instant claim 20 requires the expression which is not at a normal level is overexpression. This phrase cannot be reasonably interpreted as set forth in the §112(b) rejection above. However, reference claim 6 claims CD106 is not expressed at a normal level and reference claim 3 teaches “not a normal level” includes overexpression. While reference claim 3 claims HDAC is overexpressed, the claim sets forth a definition of what is included in the phrase “is not at a normal level” and so would render overexpression of CD106 in reference claim 6 an obvious variation.
Instant claim 21 requires administering an anti-CD106 antibody, which is anticipated by reference claim 5.
Instant claim 24 requires treatment of a diabetic complication. Reference claim 8 teaches the symptom associated with DM includes, e.g., neuropathy, which is a diabetic complication (diabetic neuropathy; see also instant claim 25).
Instant claim 25 requires treatment of certain disorders/symptoms which are identical to those treated in reference claim 8.
Instant claim 26 requires the migration agent causes the HSC to migrate from a niche. First, this is an inherent result of the migration agent being administered. Second, reference claim 9 anticipates this result.
Instant claim 27 requires a class of migration agent, which is anticipated by reference claim 10.
Instant claim 28 requires certain migration agents, which are anticipated by reference claim 11.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
No double patenting rejection was made over application 17/769706 because the reference claims are 1) a diagnostic method with no treatment step or 2) treating DM with the same HSC suppressing agent as instantly claimed but absent the migration agent. While the instant claims anticipate the ‘706 claims, the reverse is not true. See below for the reasons including the migration agent is non-obvious.
Allowable Subject Matter
There is no prior art rejection of the instant claims. The closest prior art is Miwako (NPL citation 5 on IDS 4/15/22), which teaches that CD106-expressing HSCs are the cause of diabetic neuropathy. Weighing in favor of obviousness is the explicit suggestion that these CD106+ HSCs are a therapeutic target for diabetic neuropathy (DN). One of ordinary skill in the art set to inhibit/remove CD106+ HSCs to treat DN would have found it obvious to select any number of known CD106 antibodies with a reasonable expectation that the antibody would remove/suppress the positive cells, thereby treating the cause of DN. Weighing against obviousness is that the instant claims are a combination of HSC inhibitor and stem cell migration agent. Thus, the instant claims require one agent which inhibits the function of HSCs with another agent that causes those HSCs to migrate. The art does not provide a rationale for migrating a non-functional cell and so there does not appear to be a prima facie reason to combine these two therapeutics. Additionally, the teachings of Miwako are directed to treatment of DN, whereas the instant specification provides additional evidence that these same abnormal HSCs reproduce other aspects of diabetes mellitus even in the absence of increased glucose. This is considered secondary evidence relevant to obviousness in that such a treatment is not expected to only treat DN as disclosed in Miwako, but to treat DM as a whole. Further, since these cells are sufficient on their own to cause DM as described by the instant specification, the instant treatment is reasonably expected to be capable of preventing DM.
The Examiner also searched for DM treatments that combine any of the instantly disclosed suppressing agents (HDAC inhibitors, proinsulin inhibitors, CD34 inhibitors, etc) in combination with the migration agents in claim 28. The art includes these agents in the context of treating cancer and other diseases. When they suggest diabetes, it is generally in a laundry list of conditions and include a similar laundry list of therapeutics. See for example US 20180228907, US20180170897, and US20150239974 (form 892). Taken as a whole, the claims are deemed non-obvious over the prior art.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Applicant has cited the abstract provided on the IDS (4/15/22) by Miwako for the 18th Meeting of the JSRM. Note that the Office does not currently have any evidence regarding the information (posters, talks, etc.) which may or may not have been disclosed at that meeting. This abstract has been identified with “et al.” with no further indication as to whom else was part of this disclosure in addition to Miwako.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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/Adam Weidner/ Primary Examiner, Art Unit 1675