DETAILED ACTION
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 .
Application Status
2. Applicant’s amendment and response, submitted January 12, 2026, has been reviewed by the examiner and entered of record in the file.
3. Claim 1 is amended, and claims 2-4, 6, and 9 are cancelled.
4. Claims 18, 19, 21, and 23-27, drawn to a process of preparation and methods of use, were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention without traverse, there being no allowable generic or linking claim.
5. Claims 1, 5, 7, 8, 10-17 and 20 are under examination and are the subject of this office action.
Drawings
6. The corrected drawings received on January 12, 2026 replacing Figures 3-5, 16, 17, 20, and 23-30, are acceptable. Therefore the previous objection of said drawings is withdrawn.
Previous Claim Rejections - 35 USC § 112(a)
7. Claims 1-14, 17 and 20 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as lacking enablement for the full scope of dendrimer species encompassed by the Formula of the claims, as recited.
8. In view of Applicant’s amendment to limit the scope of the recited dendrimer such that the central core § is
,
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, B is phenyl, and J is phenyl, the previous enablement rejection is withdrawn.
Previous Claim Rejections - 35 USC § 112(b)
9. Claims 1-14 and 20 were previously 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.
10. Claim 1 was previously rejected as being indefinite regarding the limitation “a central core § of valence m, where m is an integer greater than or equal to 1” because the term “§” was not defined by the claim. In view of Applicant’s amendment to define the central core moiety § as the following group
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the previous indefiniteness rejection is overcome and is withdrawn.
11. The rejection of claims 2-14 and 20 as being dependent upon and including all of the limitations of claim 1 is also withdrawn.
Specification
12. The abstract of the disclosure is objected to for reciting, “[t]he present invention relates to new dendrimers… [language omitted],” in line 1. It is suggested that the term “new” be deleted from the language of the abstract. Once the determination of the novelty of a claimed invention has been established and the disclosure of the invention made public and/or patented, the claimed invention is no longer novel, since the scope of the invention no longer embraces what is considered “new.” Thus, the incorporation of “new” into the language of the abstract is not appropriate. Appropriate correction is required. See MPEP § 608.01.
13. The specification is objected to for the following reasons:
(a) The Specification is objected to for reciting, “[t]he present invention relates to new dendrimers… [language omitted],” (at least paragraph [0001]). It is suggested that the term “new” be deleted from the language of the specification. Once the determination of the novelty of a claimed invention has been established and the disclosure of the invention made public and/or patented, the claimed invention is no longer novel, since the scope of the invention no longer embraces what is considered “new.” Thus, the incorporation of “new” into the language of the specification is not appropriate. Appropriate correction is required. See MPEP § 608.01.
(b) Several of the reaction schemes and compound structures in the Specification are unclear/ fuzzy such that it is difficult to read each scheme and/or structure, as follows:
Scheme 1 (page 84), Scheme 2 (page 102), Scheme 3 (page 108), Scheme 4 (page 122), and Scheme 5 (page 135), as well as the compound structures depicted on pages 34, 35, 45, 103-107 and 122-132. Correction is required.
Election/Restrictions
14. Claims 1, 5, 7, 8, 10-17 and 20 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(b), claims 18 and 19, (drawn to the invention of Group II), directed to the process of making the allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104. Claims 21 and 23-27, directed to the inventions of Group III, require all the limitations of an allowable product claim, and have NOT been rejoined.
Because a claimed invention previously withdrawn from consideration under 37 CFR 1.142 has been rejoined, the restriction requirement between groups I and II as set forth in the Office action mailed on April 30, 2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, Applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
New Claim Rejections - 35 USC § 112
15. 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.
16. Claims 18 and 19 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.
17. Claim 18 is unclear in the following aspects:
a. In step (a), the claim recites “preparing an intermediate of the following formula:” but fails to define any steps involved in said preparation such that is it unclear how the intermediate is obtained.
b. In claim 18, step (c), recites the limitation "the product" in line 1. However there is insufficient antecedent basis for this limitation in the claim because there is no recitation of “a product” in step b.
18. Claim 19 is unclear in the following aspects:
a. in step (a), the claim recites “preparing a fragment comprising a generation chain, an intermediate chain and an end group of the following formula:” but fails to define any steps involved in said preparation such that is it unclear how the intermediate is obtained.
b. step (b) recites the limitation “a halogenated central core §,” however the term “§” renders the claim indefinite. The term “§” is not defined by the claim, such that one of ordinary skill in the art would not be reasonably apprised of the scope of the invention, and the metes and bounds of the claim cannot be ascertained.
In view of a broadest reasonable interpretation of step b (based on the description at pages 15-17 of the Specification and the amendment to claim 1), the central core “§” is construed to mean:
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.
New Claim Rejections - 35 USC § 112(a)
19. 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.
20. Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the dendrimer species embraced by claim 1 and those embodied by the instant Specification, is not considered enabled for a method of reacting an intermediate of step (a) with P(E)X3 to obtain a product and further reacting said product with any fragment comprising an intermediate chain and an end group in order to prepare a dendrimer according to claim 1, as recited. 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.
21. As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), the standard to be applied when determining enablement is achieved by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below.
22. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.” In the instant case, the claimed invention pertains to a method of preparing an n generation dendrimer according to claim 1, comprising a central core “
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” having valence of 6, and having branching generation chains around the core according to formula (CG):
-A-B-CH2-N(D)-P(<)(=E)
and an intermediate chain at the end of each generation chain according to formula (CI):
-G-J-L-
and an end group at the end of each intermediate chain according to formula (T):
-V(-W1)(-W2)
comprising reacting the intermediate compound of step (a) with P(E)X3 to obtain a product, and reacting said product with any fragment comprising an intermediate chain and an end group.
23. The State of the Prior Art and the Relative Skill of those in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
24. As discussed above, the instantly claimed invention pertains to the preparation of an n generation dendrimer according to the formula defined in claim 1, which are alleged by the Specification to act as anti-inflammatory agents. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that - due in large part to the strict requirement of complementarity between a compound and its corresponding binding site on a target receptor or enzyme - compounds, in the vast majority of cases, demonstrate a remarkably high correlation between their structure, specificity and ability to produce a pharmacological effect. At the same time, it would have also been generally assumed that two compounds with similar chemical properties would exhibit similar biological effects. Thus, given a series of compounds that are shown to exert an activity of interest (or given a target of interest), the ordinarily skilled artisan would have expected that a limited genus of related compounds (e.g., compounds exhibiting near equal molecular shapes and volumes, approximately the same distribution of electrons, and similar physical properties such as hydrophobicity, etc) would interact with the given target to elicit a related biological response.
25. Accordingly, at the time the invention was made, the relative skill of those in the art tasked with identifying compounds exerting an activity of interest would have been high, as the ordinarily skilled artisan would have had, at minimum, a Ph.D. and experience with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods. Deciding which technique to use would have been determined by the skilled artisan’s knowledge regarding the compound and target of interest. Ligand based drug design relies on knowledge of a compound or compounds of interest (i.e., ligands) to derive new compounds that will, in theory, similarly interact with the target of interest to elicit the activity of interest. Conversely, structure-based drug design relies on knowledge of the three-dimensional structure of the target of interest (i.e., receptor, ion channel, or enzyme) to derive new compounds that will, in theory, interact with the target of interest to elicit the activity of interest. In either case, the compounds derived from these techniques (applied alone or in combination) are then subjected to in vitro testing for validation.
26. The Level of Predictability in the Art: Once a compound has been identified by ligand based and/or structure-based drug design methods as potentially binding to the target molecule, it must be evaluated. However, as discussed by Anderson (Chem and Biol 10:787-797, 2003), “it is important to consider that the ranking assigned by the scoring function is not always indicative of a true binding constant, since the model of the target:ligand interaction is inherently an approximation. Usually, several molecules which scored well during the docking run are evaluated in further tests since even the top scoring molecule could fail in vitro assays… Finally, leads are brought into the wet lab for biochemical evaluation” (Anderson, page 794, Column 1). By that point, as noted by Thiel (Nature Biotechnol 2:513-519, 2004), “libraries are small and hit rates are on the order of one in ten” (Thiel, page 517, Column 2). This low level of predictability is not surprising considering that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, modifying even a single atom in a compound can dramatically change the compound’s overall structure and - even though complementarity in one portion of the compound might be improved by the chemical revision - the overall binding or activity might be severely compromised. This is certainly true in the case of phosphorous dendrimers which, as disclosed by Hayder et al. (Science Transl Med 2011), demonstrate significantly altered activity following minor modifications to the structure. Hayder et al. teach that dendrimer ABP was initially compared to two other dendrimer based systems, dendrimer azamonophosphonate (AMP) and dendrimer polypropyleneimine (PPI), for antiarthritic activity in mice, wherein dendrimer AMP is a phosphorus-based dendrimer that is similar in structure and composition to dendrimer ABP, yet demonstrates significantly improved anti-inflammatory effects in vivo over the other two dendrimers (see page 2 under “Results”).
27. The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification discloses the synthesis of less than 10 dendrimers, 12-G’’’1BOC, 12-G’’’1-HTFA, 12-G’’’2-BOC, 12-G’’’1-HTFA, 3-G’1(ONa), 4-G’1(ONa), 5-G’1(ONa), 13-G2(OMe), and 14-G2(OMe) (pages 154-160). Thus, support cannot be found for the preparation of a dendrimer according to the formula of claim 1, employing the full scope of any fragment comprising an intermediate chain and an end group, as instantly claimed.
28. Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “when a compound or composition claim is not limited by a recited use, any enabled use that would reasonably correlate with the entire scope of that claim is sufficient to preclude a rejection for nonenablement based on how to use” (emphasis added). For purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation.”
29. As to the first inquiry, as discussed above, the claims are drawn to an n generation dendrimer according to claim 1, comprising a central core “§” having valence of 6, having branching generation chains around the core according to formula (CG):
-A-B-CH2-N(D)-P(<)(=E)
and an intermediate chain at the end of each generation chain according to formula (CI):
-G-J-L-
and an end group at the end of each intermediate chain according to formula (T):
-V(-W1)(-W2)
and wherein n is an integer of from 1 to 12.
Considering that the genus of fragments embraced to prepare said dendrimer is virtually without limit, i.e., the fragment can be any compound comprising an intermediate chain and an end group. The genus is virtually without limit, embracing hundreds of millions of potential compounds if not billions, thus it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses the preparation of less than 10 dendrimers. As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
30. Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to the preparation of an n generation dendrimer. In the instant case, the complexity of the claimed subject matter is exacerbated by the broadness of the scope of dendrimers with respect to the disclosure since the claim presently encompass hundreds of millions of potential fragments, and potentially billions, whereas the instant Specification discloses the preparation of less than ten dendrimer species. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan (armed with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods) could not reasonably predict which of the hundreds of millions of fragments encompassed by the claim could be utilized in the preparation of a dendrimer of claim 1, based on the limited disclosure of less than 10 synthesized dendrimers.
As such, the only way to ascertain which of the hundreds of millions, and potentially billions, of claimed fragments encompassed by the claim are usable for the recited preparation based on the limited disclosure would require undue experimentation.
As such, claim 18 is rejected.
Conclusion
31. Claims 1, 5, 7, 8, 10-21 and 23-27 are present in the application. Claims 21 and 23-27 are presently withdrawn from consideration as directed to nonelected subject matter. Claims 18 and 19 are rejected. Claims 1, 5, 7, 8, 10-17 and 20 appear allowable over the prior art of record.
32. 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.
33. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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