Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
This application is a continuation of PCT/US2022/014729, filed February 1, 2022, which claims benefit of provisional application 63/144379, filed February 1, 2021. Claims 1-9, 11-19, 24, and 28 are pending in this application and examined on the merits herein. Applicant’s preliminary amendment submitted October 25, 2023 is acknowledged wherein claims 4-7, 9, 11-14, 16-19, 24, and 28 are amended and claims 10, 20-23, 25-27, and 29 are canceled.
Drawings
The drawings are objected to because the structures in figure 1A are presented in sufficiently low resolution that some portions of the chemical structures are illegible. 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 Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 24 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of implanting mesenchymal stem cells, does not reasonably provide enablement for treating, reducing the onset of, or preventing any possible health condition. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
Nature of the invention: The invention of claim 24 is a therapeutic method. In order to be enabled for the full scope of said method, one of ordinary skill in the art would have to reasonably be able to treat the full scope of disease using the claimed compositions.
The state of the prior art: Hyaluronic acid and PEG hydrogels having broadly similar physical characteristics to the claimed polymer hydrogels are known in the art. For example, Cao et al. (Reference included with PTO-892) discloses a copolymer of chitosan and PEG as useful for cartilage tissue engineering. Similarly, Sedova et al. (Reference included with PTO-892) discloses a hyaluronic acid-PEG hydrogel as being a potentially useful biomaterial for tissue engineering and supporting the growth of implanted cells. (p. 63 left column) Additionally, as described by Barry et al. and Kim et al. (both included with PTO-892) cell-based tissue engineering methods involving implantation of mesenchymal stem cells can be used as an effective method of tissue repair. Therefore one skilled in the art would regard a HA/PEG hydrogel and a material comprising stem cells supported in a scaffold of such material as being useful for certain methods of tissue repair to treat conditions including osteoarthritis, but would not necessarily have any expectation of using HA hydrogels as a general preventative or curative treatment for all possible conditions, as not all disease conditions can be treated by implantation of mesenchymal stem cells.
The relative skill of those in the art: The relative skill of those in the art is high.
The predictability or unpredictability of the art: While certain classes of therapies exist that can treat related groups of diseases, for example mesenchymal stem cells for treatment of tissue injury or degeneration, there does not exist any particular pathological mechanism or therapeutic agent common to all diseases. Therefore evidence of efficacy of a therapy at treating one class of disease conditions does not necessarily translate into methods of treating unrelated conditions.
The Breadth of the claims: Claim 24 is generic to a wide variety of different therapeutic methods, as it imposes no limit on the characteristics of the particular disease being treated.
The amount of direction or guidance presented: The present disclosure describes hydrogels according to the present claims as useful for treating a number of diseases, and generally as injectable compositions for delivery of therapeutic agents. (p. 24 paragraph 85 – p. 25 paragraph 89) However, the actual utility demonstrated for the claimed hydrogels (e.g. examples 2-5 on pp. 33-39) describe using the hydrogel for encapsulation of mesenchymal stem cells. Therefore the guidance provided is specific only to methods of treatment involving injection of MSC-containing materials.
The presence or absence of working examples: No specific working examples are provided for the actual treatment of diseases in a human subject or animal model. While examples are provided they involve in vitro cell cultures rather than actual living subjects.
The quantity of experimentation necessary: In order to practice the full scope of claim 24, one skilled in the art would have to be capable of treating a wide variety of unrelated health conditions using methods involving the hydrogel compositions of claims 1 and 9. The present disclosure as filed demonstrates with a reasonable expectation of success that the claimed hydrogels can be used to encapsulate mesenchymal stem cells for the purpose of tissue repair. However it does not clearly demonstrate how such a method can be used to treat other health conditions, for example viral infections or psychiatric disorders, wherein the application of mesenchymal stem cells would not be expected to be beneficial. Actually extending the known and expected utility of these methods to the broader scope of every possible health condition would require an undue burden of unpredictable research necessary to implement the claimed therapeutic and preventative methods.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance in the disclosure, Applicants fail to provide information sufficient to practice the claimed invention for all possible health conditions.
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 1-9, 11-19, 24, and 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.
Independent claim 1, from which all other claims depend, describes a composition comprising a “first polymer backbone” and a “second polymer backbone.” The first polymer backbone is defined as containing “a hyaluronic acid backbone functionalized with an aliphatic aldehyde” and “:a hyaluronic backbone functionalized with a hydrazide,” while the second polymer backbone is defined as “at least one 8-arm poly(ethylene glycol)”. As written, it is unclear how many discrete chemical species these represent and what relationship they bear to one another. Firstly, it is unclear whether the “first polymer backbone,” which is referred to in one place as a single species and in another as a mixture of two species, is infringed by a single hyaluronic acid randomly substituted with both aliphatic aldehydes and hydrazides, a block copolymer made of two different sections of backbone, one substituted with aliphatic aldehyde and the other substituted with hydrazide, a mixture of two different hyaluronic acids, one substituted with aliphatic aldehyde and the other with hydrazide, or some combination of the aforementioned embodiments. In addition, the claim contains an additional limitation requiring that the combination of the two network backbones produces a hybrid network hydrogel. It is unclear whether this limitation requires that the composition be one in which the various components are chemically reacted with one another to formed a crosslinked network, or whether it merely requires that the composition be capable of forming such a network.
Dependent claim 6 furthermore refers to percentages of “total crosslink concentration” as 25% by weight being between an aliphatic aldehyde and 75% by weight of total crosslink concentration in the second polymer backbone comprising at least one 8-arm PEG. Firstly, these terms lack antecedent basis in both claim 6 and base claim 1. Nowhere in these claims does the claim language specifically define the composition as containing crosslinks. While claim 1 describes aldehydes and hydrazides, which could in theory react to form hydrazones, these two chemical groups are described as unreacted species rather than as the reaction product of these two species together. Furthermore while claim 1 refers to a “hybrid network hydrogel,” this term is never defined in such a way that would clearly define it as requiring any chemical crosslinks.
Still further, the terms “75% by weight of total crosslink concentration” and “25% by weight of total crosslink concentration” are indefinite when used to refer to the crosslink composition of a polymer. Since a crosslink is a structural feature of a larger macromolecular entity, it does not have a clearly defined molecular weight in the same way that a molecule does. The manner in which these percentages ae defined could be taken as referring either to the percentages of different crosslinks which involve the recited molecular entities, or alternately to the relative weights of different species (i.e. first and second backbone polymers) within the composition. Since there is no way to clearly reconcile this contradiction, claim 6 is indefinite.
Dependent claim 13 requires that the composition comprise a releasable active agent “Before, after, or during degradation of the composition after administering the composition to the subject.” Because this claim, which is directed to a composition of matter, is referring to a hypothetical future state of the composition, it cannot be clearly determined whether the claim actually requires that the claimed composition comprise the active agent at the time of infringement.
Dependent claims 17 and 18, which are directed to processes and dependent from claim 14, require as their sole additional limitation that stress relaxation of the hybrid network hydrogel “is increased” or “is decreased” by combining the components of the hydrogel in a particular manner. Because these limitations are written in the passive voice, they do not clearly define additional process steps. However, because the base claim 14 does not specifically describe increasing or decreasing stress relaxation of the network hydrogel, this limitation also does not clearly and unambiguously define a characteristic of the “combining” step recited in claim 14.
For these reasons the claims are seen to be indefinite.
Conclusion
No claims are allowed in this action.
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/ANDREA OLSON/Primary Examiner, Art Unit 1693 3/2/2026